Pharmacology

When vancomycin doesn’t work, ceftaroline may be a viable alternative for patients with nosocomial pneumonia (NP) due to methicillin-resistant Staphylococcus aureus (MRSA), say researchers from Summa Akron City Hospital in Ohio. They point out that ceftaroline is already approved for treatment of community-acquired bacterial pneumonia (CABP) due to Streptococcus pneumonia and MRSA (methicillin-susceptible isolates only), among other pathogens. Two large prospective, randomized clinical trials found ceftaroline effective and well tolerated in patients with CABP. However, its use in MRSA NP is unknown, the researchers say, which is why they retrospectively reviewed the cases of 10 patients admitted to their hospital who received ceftaroline for MRSA NP from September 2011 to September 2012.

Related: VA Drastically Cuts Rates of MRSA Infection

Of the 10 patients, 6 had health care-associated pneumonia, 3 had hospital-acquired pneumonia, and 1 had ventilator-associated pneumonia. All 10 had respiratory cultures positive for MRSA. Eight patients had MRSA isolates with resistance patterns consistent with traditional health care-associated MRSA strains, and 2 were consistent with community-acquired MRSA.

Related: Risk of Readmission After Pneumonia

In all, 9 patients received prior anti-MRSA therapy before the initiation of ceftaroline. Eight patients received ceftaroline 600 mg infused over 1 hour every 12 hours; 2 patients received renally adjusted lower doses. Therapy lasted from 4 to 28 days.

Related: HIV-Negative Patients at Risk for Pneumocystosis

Three patients died due to advanced age and multiple medical conditions after stopping antibiotic treatment and moving to palliative care. The remaining 7 patients responded well to the ceftaroline treatment, although 1 had microbiological and clinical relapse. The drug was well tolerated.

Although their case series is small and uncontrolled, the researchers say it suggests the potential of ceftaroline as an alternative agent for MRSA NP.

Source
Pasquale TR, Tan MJ, Trienski TL, File TM Jr. J Chemother. 2015;27(1):29-34.
doi: 10.1179/1973947813Y.0000000156.

When vancomycin doesn’t work, ceftaroline may be a viable alternative for patients with nosocomial pneumonia (NP) due to methicillin-resistant Staphylococcus aureus (MRSA), say researchers from Summa Akron City Hospital in Ohio. They point out that ceftaroline is already approved for treatment of community-acquired bacterial pneumonia (CABP) due to Streptococcus pneumonia and MRSA (methicillin-susceptible isolates only), among other pathogens. Two large prospective, randomized clinical trials found ceftaroline effective and well tolerated in patients with CABP. However, its use in MRSA NP is unknown, the researchers say, which is why they retrospectively reviewed the cases of 10 patients admitted to their hospital who received ceftaroline for MRSA NP from September 2011 to September 2012.

Related: VA Drastically Cuts Rates of MRSA Infection

Of the 10 patients, 6 had health care-associated pneumonia, 3 had hospital-acquired pneumonia, and 1 had ventilator-associated pneumonia. All 10 had respiratory cultures positive for MRSA. Eight patients had MRSA isolates with resistance patterns consistent with traditional health care-associated MRSA strains, and 2 were consistent with community-acquired MRSA.

Related: Risk of Readmission After Pneumonia

In all, 9 patients received prior anti-MRSA therapy before the initiation of ceftaroline. Eight patients received ceftaroline 600 mg infused over 1 hour every 12 hours; 2 patients received renally adjusted lower doses. Therapy lasted from 4 to 28 days.

Related: HIV-Negative Patients at Risk for Pneumocystosis

Three patients died due to advanced age and multiple medical conditions after stopping antibiotic treatment and moving to palliative care. The remaining 7 patients responded well to the ceftaroline treatment, although 1 had microbiological and clinical relapse. The drug was well tolerated.

Although their case series is small and uncontrolled, the researchers say it suggests the potential of ceftaroline as an alternative agent for MRSA NP.

Source
Pasquale TR, Tan MJ, Trienski TL, File TM Jr. J Chemother. 2015;27(1):29-34.
doi: 10.1179/1973947813Y.0000000156.

When vancomycin doesn’t work, ceftaroline may be a viable alternative for patients with nosocomial pneumonia (NP) due to methicillin-resistant Staphylococcus aureus (MRSA), say researchers from Summa Akron City Hospital in Ohio. They point out that ceftaroline is already approved for treatment of community-acquired bacterial pneumonia (CABP) due to Streptococcus pneumonia and MRSA (methicillin-susceptible isolates only), among other pathogens. Two large prospective, randomized clinical trials found ceftaroline effective and well tolerated in patients with CABP. However, its use in MRSA NP is unknown, the researchers say, which is why they retrospectively reviewed the cases of 10 patients admitted to their hospital who received ceftaroline for MRSA NP from September 2011 to September 2012.

Related: VA Drastically Cuts Rates of MRSA Infection

Of the 10 patients, 6 had health care-associated pneumonia, 3 had hospital-acquired pneumonia, and 1 had ventilator-associated pneumonia. All 10 had respiratory cultures positive for MRSA. Eight patients had MRSA isolates with resistance patterns consistent with traditional health care-associated MRSA strains, and 2 were consistent with community-acquired MRSA.

Related: Risk of Readmission After Pneumonia

In all, 9 patients received prior anti-MRSA therapy before the initiation of ceftaroline. Eight patients received ceftaroline 600 mg infused over 1 hour every 12 hours; 2 patients received renally adjusted lower doses. Therapy lasted from 4 to 28 days.

Related: HIV-Negative Patients at Risk for Pneumocystosis

Three patients died due to advanced age and multiple medical conditions after stopping antibiotic treatment and moving to palliative care. The remaining 7 patients responded well to the ceftaroline treatment, although 1 had microbiological and clinical relapse. The drug was well tolerated.

Although their case series is small and uncontrolled, the researchers say it suggests the potential of ceftaroline as an alternative agent for MRSA NP.

Source
Pasquale TR, Tan MJ, Trienski TL, File TM Jr. J Chemother. 2015;27(1):29-34.
doi: 10.1179/1973947813Y.0000000156.

The FDA has expanded the approved use of nivolumab to include patients with metastatic squamous non-small cell lung cancer (NSCLC). As the most common type of lung cancer, NSCLC affects nearly 90% of patients with lung cancer.

Used to treat tumor progression on or after platinum-based chemotherapy, nivolumab blocks the signals by which lung cancer inactivates T cells, thereby helping to restore the immune response.

Related: Timely Assessment of Cancer Symptoms

In a randomized trial comparing nivolumab with docetaxel in 272 patients, those who received nivolumab lived, on average, 3.2 months longer than did those on docetaxel (9.2 months vs 6 months). Another study followed 117 patients with metastatic squamous NSCLC who previously had platinum-based therapy and one or more additional systemic therapies. Of those, 17 patients (15%) experienced partial shrinkage or complete disappearance of the tumor; in 10 patients, the response lasted ≥ 6 months. In that trial, the median time to onset of response was 3.3 months after the start of treatment. The duration of response ranged from 1.9 to 11.5 months.

Related: Pulmonary Vein Thrombosis Associated With Metastatic Carcinoma

The most frequent adverse effects (AEs) are fatigue, shortness of breath, musculoskeletal pain, reduced appetite, cough, nausea, and constipation. Because of the mode of action, nivolumab can cause the immune system to attack normal organs and tissues, which means some of the most serious AEs are severe immune-mediated diseases, such as pneumonitis, colitis, and hepatitis.

Related: On the Scent of Cancer

Nivolumab was approved in 2014 for IV use, based on tumor response rate and durability of response. According to the manufacturer, Bristol-Myers Squibb Company, which conducted a study of patients with advanced melanoma, the single-arm, noncomparative interim analysis of the first 120 patients who received the drug showed a 32% response rate: 4 patients achieved a complete response and 34 had a partial response. The response lasted from 2 to 10-plus months; 13 patients had ongoing responses of ≥ 6 months.

Sources
U.S. Food and Drug Administration. FDA expands approved use of Opdivo to treat lung cancer [press release]. Silver Spring, MD: U.S. Food and Drug Administration; March 4, 2015.

OPDIVO [package insert]. Princeton, NJ: Bristol-Meyers Squibb Company; 2015.

Food and Drug Administration. FDA approves Opdivo for advanced melanoma [press release]. Silver Spring, MD: U.S. Food and Drug Administration; December 22, 2014.

The FDA has expanded the approved use of nivolumab to include patients with metastatic squamous non-small cell lung cancer (NSCLC). As the most common type of lung cancer, NSCLC affects nearly 90% of patients with lung cancer.

Used to treat tumor progression on or after platinum-based chemotherapy, nivolumab blocks the signals by which lung cancer inactivates T cells, thereby helping to restore the immune response.

Related: Timely Assessment of Cancer Symptoms

In a randomized trial comparing nivolumab with docetaxel in 272 patients, those who received nivolumab lived, on average, 3.2 months longer than did those on docetaxel (9.2 months vs 6 months). Another study followed 117 patients with metastatic squamous NSCLC who previously had platinum-based therapy and one or more additional systemic therapies. Of those, 17 patients (15%) experienced partial shrinkage or complete disappearance of the tumor; in 10 patients, the response lasted ≥ 6 months. In that trial, the median time to onset of response was 3.3 months after the start of treatment. The duration of response ranged from 1.9 to 11.5 months.

Related: Pulmonary Vein Thrombosis Associated With Metastatic Carcinoma

The most frequent adverse effects (AEs) are fatigue, shortness of breath, musculoskeletal pain, reduced appetite, cough, nausea, and constipation. Because of the mode of action, nivolumab can cause the immune system to attack normal organs and tissues, which means some of the most serious AEs are severe immune-mediated diseases, such as pneumonitis, colitis, and hepatitis.

Related: On the Scent of Cancer

Nivolumab was approved in 2014 for IV use, based on tumor response rate and durability of response. According to the manufacturer, Bristol-Myers Squibb Company, which conducted a study of patients with advanced melanoma, the single-arm, noncomparative interim analysis of the first 120 patients who received the drug showed a 32% response rate: 4 patients achieved a complete response and 34 had a partial response. The response lasted from 2 to 10-plus months; 13 patients had ongoing responses of ≥ 6 months.

Sources
U.S. Food and Drug Administration. FDA expands approved use of Opdivo to treat lung cancer [press release]. Silver Spring, MD: U.S. Food and Drug Administration; March 4, 2015.

OPDIVO [package insert]. Princeton, NJ: Bristol-Meyers Squibb Company; 2015.

Food and Drug Administration. FDA approves Opdivo for advanced melanoma [press release]. Silver Spring, MD: U.S. Food and Drug Administration; December 22, 2014.

The FDA has expanded the approved use of nivolumab to include patients with metastatic squamous non-small cell lung cancer (NSCLC). As the most common type of lung cancer, NSCLC affects nearly 90% of patients with lung cancer.

Used to treat tumor progression on or after platinum-based chemotherapy, nivolumab blocks the signals by which lung cancer inactivates T cells, thereby helping to restore the immune response.

Related: Timely Assessment of Cancer Symptoms

In a randomized trial comparing nivolumab with docetaxel in 272 patients, those who received nivolumab lived, on average, 3.2 months longer than did those on docetaxel (9.2 months vs 6 months). Another study followed 117 patients with metastatic squamous NSCLC who previously had platinum-based therapy and one or more additional systemic therapies. Of those, 17 patients (15%) experienced partial shrinkage or complete disappearance of the tumor; in 10 patients, the response lasted ≥ 6 months. In that trial, the median time to onset of response was 3.3 months after the start of treatment. The duration of response ranged from 1.9 to 11.5 months.

Related: Pulmonary Vein Thrombosis Associated With Metastatic Carcinoma

The most frequent adverse effects (AEs) are fatigue, shortness of breath, musculoskeletal pain, reduced appetite, cough, nausea, and constipation. Because of the mode of action, nivolumab can cause the immune system to attack normal organs and tissues, which means some of the most serious AEs are severe immune-mediated diseases, such as pneumonitis, colitis, and hepatitis.

Related: On the Scent of Cancer

Nivolumab was approved in 2014 for IV use, based on tumor response rate and durability of response. According to the manufacturer, Bristol-Myers Squibb Company, which conducted a study of patients with advanced melanoma, the single-arm, noncomparative interim analysis of the first 120 patients who received the drug showed a 32% response rate: 4 patients achieved a complete response and 34 had a partial response. The response lasted from 2 to 10-plus months; 13 patients had ongoing responses of ≥ 6 months.

Sources
U.S. Food and Drug Administration. FDA expands approved use of Opdivo to treat lung cancer [press release]. Silver Spring, MD: U.S. Food and Drug Administration; March 4, 2015.

OPDIVO [package insert]. Princeton, NJ: Bristol-Meyers Squibb Company; 2015.

Food and Drug Administration. FDA approves Opdivo for advanced melanoma [press release]. Silver Spring, MD: U.S. Food and Drug Administration; December 22, 2014.

Hyponatremia is an uncommon adverse effect of psychotropic drugs, thought to be caused by the release of an antidiuretic hormone. And serotonergic drugs are known to cause syndrome of inappropriate antidiuretic hormone secretion (SIADH). But the relationship between SIADH and antipsychotics is not well understood, say clinicians from University College of Medical Science and Guru Teg Bahadur Hospital and Institute of Human Behaviour and Allied Sciences, both in Delhi, India. Their own case report should add to the body of knowledge, they say.

They reported the case of a patient who developed SIADH after starting risperidone. The patient, a woman aged 22 years, had been experiencing psychotic symptoms for a year, including persecutory beliefs and hallucinations. She was treatment naïve, having visited only faith healers, with no contact with medical or psychiatric services. The mental status examination result was consistent with the diagnosis of paranoid schizophrenia. A physical examination did not reveal any sign of physical illness, nor did routine blood tests reveal any abnormalities; she did not have polydipsia.

Related: Lurasidone Approved for Bipolar Disorder

She was started on risperidone tablet 2 mg/d, which she tolerated well. After 3 days, the dosage was increased to 4 mg/d. She was not prescribed any other medications.

After 5 days on risperidone, she had an episode of generalized tonic-clonic seizures and was hospitalized. She was drowsy, but her vital signs and physical examination results were normal. Laboratory results revealed her blood sugar was 90 mg/dL; sodium, 118 mEq/dL; potassium, 4.1 mEq/dL; uric acid, 2.0 mg/dL; calcium, 8.4 mg/dL; osmolarity, and 258 mOsm/kg of water. Her blood urea nitrogen was 10 mEq/dL, urinary sodium was 34 mEq/L; urine routine and microscopic examination were normal. The serum cortisol level and thyroid profile were also normal.

After all the tests were done, the patient was diagnosed with SIADH. The risperidone was stopped. She was treated for the hyponatremia, and by the third day, her serum sodium had increased to 134 mEq/dL. Her mental status had returned to normal.

Related: Fiduciary Services for Veterans With Psychiatric Disabilities

The authors note that SIADH is the cause of hyponatremia in about one-third of cases. Various psychotropic and antipsychotic drugs, both typical and atypical, have been reported to cause SIADH, but the mechanism is not clear. However, because their patient’s blood pressure was normal and she was on risperidone for only 5 days (making the possibility of D2 receptor supersensitivity unlikely), the authors hypothesize that the SIADH was mediated by the action of risperidone on 5-HT receptors.

During clinical trials of oral risperidone, the authors say, a small percentage of adults and children reported thirst, and risperidone was suspected of causing polydipsia. That mechanism may be relevant to the development of hyponatremia, they suggest. In premarketing trials, some patients also had seizures thought to be due to oral risperidone. Two cases of seizures were associated with hyponatremia. For that reason, risperidone should be used cautiously in patients with a history of seizure, the authors advise.

Related: Veterans' Use of Designer Cathinones and Cannabinoids

In the case of their patient, clinical history and investigations supported the diagnosis of SIADH. The lack of a history of polydipsia, combined with the onset of hyponatremia with seizures shortly after starting risperidone and the rapid correction of serum sodium after stopping the drug make a relationship with the drug likely. The authors recommend measuring serum sodium at baseline and after starting antipsychotics as part of a routine clinical practice.

Source
Singh Ranga G, Ramkumarsingh Tomar L, Narang S, Tripathi P, Prakash Jirwal O. J Acute Med. 2014;4(3):133-134.
doi: 10.1016/j.jacme.2014.03.004.

Hyponatremia is an uncommon adverse effect of psychotropic drugs, thought to be caused by the release of an antidiuretic hormone. And serotonergic drugs are known to cause syndrome of inappropriate antidiuretic hormone secretion (SIADH). But the relationship between SIADH and antipsychotics is not well understood, say clinicians from University College of Medical Science and Guru Teg Bahadur Hospital and Institute of Human Behaviour and Allied Sciences, both in Delhi, India. Their own case report should add to the body of knowledge, they say.

They reported the case of a patient who developed SIADH after starting risperidone. The patient, a woman aged 22 years, had been experiencing psychotic symptoms for a year, including persecutory beliefs and hallucinations. She was treatment naïve, having visited only faith healers, with no contact with medical or psychiatric services. The mental status examination result was consistent with the diagnosis of paranoid schizophrenia. A physical examination did not reveal any sign of physical illness, nor did routine blood tests reveal any abnormalities; she did not have polydipsia.

Related: Lurasidone Approved for Bipolar Disorder

She was started on risperidone tablet 2 mg/d, which she tolerated well. After 3 days, the dosage was increased to 4 mg/d. She was not prescribed any other medications.

After 5 days on risperidone, she had an episode of generalized tonic-clonic seizures and was hospitalized. She was drowsy, but her vital signs and physical examination results were normal. Laboratory results revealed her blood sugar was 90 mg/dL; sodium, 118 mEq/dL; potassium, 4.1 mEq/dL; uric acid, 2.0 mg/dL; calcium, 8.4 mg/dL; osmolarity, and 258 mOsm/kg of water. Her blood urea nitrogen was 10 mEq/dL, urinary sodium was 34 mEq/L; urine routine and microscopic examination were normal. The serum cortisol level and thyroid profile were also normal.

After all the tests were done, the patient was diagnosed with SIADH. The risperidone was stopped. She was treated for the hyponatremia, and by the third day, her serum sodium had increased to 134 mEq/dL. Her mental status had returned to normal.

Related: Fiduciary Services for Veterans With Psychiatric Disabilities

The authors note that SIADH is the cause of hyponatremia in about one-third of cases. Various psychotropic and antipsychotic drugs, both typical and atypical, have been reported to cause SIADH, but the mechanism is not clear. However, because their patient’s blood pressure was normal and she was on risperidone for only 5 days (making the possibility of D2 receptor supersensitivity unlikely), the authors hypothesize that the SIADH was mediated by the action of risperidone on 5-HT receptors.

During clinical trials of oral risperidone, the authors say, a small percentage of adults and children reported thirst, and risperidone was suspected of causing polydipsia. That mechanism may be relevant to the development of hyponatremia, they suggest. In premarketing trials, some patients also had seizures thought to be due to oral risperidone. Two cases of seizures were associated with hyponatremia. For that reason, risperidone should be used cautiously in patients with a history of seizure, the authors advise.

Related: Veterans' Use of Designer Cathinones and Cannabinoids

In the case of their patient, clinical history and investigations supported the diagnosis of SIADH. The lack of a history of polydipsia, combined with the onset of hyponatremia with seizures shortly after starting risperidone and the rapid correction of serum sodium after stopping the drug make a relationship with the drug likely. The authors recommend measuring serum sodium at baseline and after starting antipsychotics as part of a routine clinical practice.

Source
Singh Ranga G, Ramkumarsingh Tomar L, Narang S, Tripathi P, Prakash Jirwal O. J Acute Med. 2014;4(3):133-134.
doi: 10.1016/j.jacme.2014.03.004.

Hyponatremia is an uncommon adverse effect of psychotropic drugs, thought to be caused by the release of an antidiuretic hormone. And serotonergic drugs are known to cause syndrome of inappropriate antidiuretic hormone secretion (SIADH). But the relationship between SIADH and antipsychotics is not well understood, say clinicians from University College of Medical Science and Guru Teg Bahadur Hospital and Institute of Human Behaviour and Allied Sciences, both in Delhi, India. Their own case report should add to the body of knowledge, they say.

They reported the case of a patient who developed SIADH after starting risperidone. The patient, a woman aged 22 years, had been experiencing psychotic symptoms for a year, including persecutory beliefs and hallucinations. She was treatment naïve, having visited only faith healers, with no contact with medical or psychiatric services. The mental status examination result was consistent with the diagnosis of paranoid schizophrenia. A physical examination did not reveal any sign of physical illness, nor did routine blood tests reveal any abnormalities; she did not have polydipsia.

Related: Lurasidone Approved for Bipolar Disorder

She was started on risperidone tablet 2 mg/d, which she tolerated well. After 3 days, the dosage was increased to 4 mg/d. She was not prescribed any other medications.

After 5 days on risperidone, she had an episode of generalized tonic-clonic seizures and was hospitalized. She was drowsy, but her vital signs and physical examination results were normal. Laboratory results revealed her blood sugar was 90 mg/dL; sodium, 118 mEq/dL; potassium, 4.1 mEq/dL; uric acid, 2.0 mg/dL; calcium, 8.4 mg/dL; osmolarity, and 258 mOsm/kg of water. Her blood urea nitrogen was 10 mEq/dL, urinary sodium was 34 mEq/L; urine routine and microscopic examination were normal. The serum cortisol level and thyroid profile were also normal.

After all the tests were done, the patient was diagnosed with SIADH. The risperidone was stopped. She was treated for the hyponatremia, and by the third day, her serum sodium had increased to 134 mEq/dL. Her mental status had returned to normal.

Related: Fiduciary Services for Veterans With Psychiatric Disabilities

The authors note that SIADH is the cause of hyponatremia in about one-third of cases. Various psychotropic and antipsychotic drugs, both typical and atypical, have been reported to cause SIADH, but the mechanism is not clear. However, because their patient’s blood pressure was normal and she was on risperidone for only 5 days (making the possibility of D2 receptor supersensitivity unlikely), the authors hypothesize that the SIADH was mediated by the action of risperidone on 5-HT receptors.

During clinical trials of oral risperidone, the authors say, a small percentage of adults and children reported thirst, and risperidone was suspected of causing polydipsia. That mechanism may be relevant to the development of hyponatremia, they suggest. In premarketing trials, some patients also had seizures thought to be due to oral risperidone. Two cases of seizures were associated with hyponatremia. For that reason, risperidone should be used cautiously in patients with a history of seizure, the authors advise.

Related: Veterans' Use of Designer Cathinones and Cannabinoids

In the case of their patient, clinical history and investigations supported the diagnosis of SIADH. The lack of a history of polydipsia, combined with the onset of hyponatremia with seizures shortly after starting risperidone and the rapid correction of serum sodium after stopping the drug make a relationship with the drug likely. The authors recommend measuring serum sodium at baseline and after starting antipsychotics as part of a routine clinical practice.

Source
Singh Ranga G, Ramkumarsingh Tomar L, Narang S, Tripathi P, Prakash Jirwal O. J Acute Med. 2014;4(3):133-134.
doi: 10.1016/j.jacme.2014.03.004.

Pneumocystis jiroveci pneumonia is associated with high mortality rates in immunocompromised patients who are HIV-negative. In-hospital mortality rates range from 50% to 86%. Although trimethoprim-sulfamethoxazole (TMP-SMX) is an effective prophylaxis, the wide spectrum of immunosuppressive conditions predisposing to pneumocystosis and the limited data available on its incidence in non–HIV-infected patients has made it hard to establish an evidence-based guideline, say researchers from Hôpital Pontchaillou, Hôpital Sud, and Université Rennes 1, all in Rennes, France. The study is the first to offer comparative estimates of pneumocystosis incidence rates across this patient population and helps narrow down the patients at greatest risk.

The researchers retrospectively analyzed all cases of documented pneumocystosis in HIV-negative patients admitted to Rennes University Hospital between 1990 and 2010. Of 293 cases of pneumocystosis, 154 (52.6%) tested negative for HIV.

Related: NSAIDs Linked to Poor Pneumonia Outcomes

One of the study’s main findings was that pneumocystosis remains a significant problem in both HIV-positive and HIV-negative immunocompromised patients. Second, the researchers found pneumocystosis is more severe in HIV-negative patients compared with HIV-positive patients, with much higher rates of intensive care unit (ICU) admission and in-ICU mortality.

The risk of pneumocystosis was particularly high (> 45 cases per 100,000 patient-years) in 2 groups: patients with inflammatory diseases/vasculitis (polyarteritis nodosa, granulomatosis with polyangiitis, polymyositis/dermatopolymyositis) and 3 hematologic malignancies (acute leukemia, chronic lymphocytic leukemia, and non-Hodgkin lymphoma).

Related: Linezolid Contributes to "Clinical Success" in MRSA Pneumonia

They found intermediate risk (25-45 cases per 100,000 patient-years) for Waldenström macroglobulinemia, multiple myeloma, and central nervous system cancer. For those patients, the researchers recommend a low threshold for prophylaxis; that is, any additional risk factor, such as prolonged use of corticosteroids, should prompt initiation of TMP-SMX. Most patients with solid tumors and inflammatory diseases were at low risk (< 25 cases per 100,000 patient-years).

Their study findings can help guide more systematic use of TMP-SMX prophylaxis, the researchers say. For high-risk patients, they suggest TMP-SMX prophylaxis may be beneficial, especially given the high morbidity and mortality rates. For intermediate-risk patients, the researchers recommend a low threshold for prophylaxis; that is, any additional risk factor, such as prolonged use of corticosteroids, should prompt initiation of TMP-SMX. But for low-risk patients, they advise avoiding routine pneumocystosis prophylaxis.

Source
Fillatre P, Decaux O, Jouneau S, et al. Am J Med. 2014;127(12):1242.e11-1242.e17.
doi: 10.1016/j.amjmed.2014.07.010.

Pneumocystis jiroveci pneumonia is associated with high mortality rates in immunocompromised patients who are HIV-negative. In-hospital mortality rates range from 50% to 86%. Although trimethoprim-sulfamethoxazole (TMP-SMX) is an effective prophylaxis, the wide spectrum of immunosuppressive conditions predisposing to pneumocystosis and the limited data available on its incidence in non–HIV-infected patients has made it hard to establish an evidence-based guideline, say researchers from Hôpital Pontchaillou, Hôpital Sud, and Université Rennes 1, all in Rennes, France. The study is the first to offer comparative estimates of pneumocystosis incidence rates across this patient population and helps narrow down the patients at greatest risk.

The researchers retrospectively analyzed all cases of documented pneumocystosis in HIV-negative patients admitted to Rennes University Hospital between 1990 and 2010. Of 293 cases of pneumocystosis, 154 (52.6%) tested negative for HIV.

Related: NSAIDs Linked to Poor Pneumonia Outcomes

One of the study’s main findings was that pneumocystosis remains a significant problem in both HIV-positive and HIV-negative immunocompromised patients. Second, the researchers found pneumocystosis is more severe in HIV-negative patients compared with HIV-positive patients, with much higher rates of intensive care unit (ICU) admission and in-ICU mortality.

The risk of pneumocystosis was particularly high (> 45 cases per 100,000 patient-years) in 2 groups: patients with inflammatory diseases/vasculitis (polyarteritis nodosa, granulomatosis with polyangiitis, polymyositis/dermatopolymyositis) and 3 hematologic malignancies (acute leukemia, chronic lymphocytic leukemia, and non-Hodgkin lymphoma).

Related: Linezolid Contributes to "Clinical Success" in MRSA Pneumonia

They found intermediate risk (25-45 cases per 100,000 patient-years) for Waldenström macroglobulinemia, multiple myeloma, and central nervous system cancer. For those patients, the researchers recommend a low threshold for prophylaxis; that is, any additional risk factor, such as prolonged use of corticosteroids, should prompt initiation of TMP-SMX. Most patients with solid tumors and inflammatory diseases were at low risk (< 25 cases per 100,000 patient-years).

Their study findings can help guide more systematic use of TMP-SMX prophylaxis, the researchers say. For high-risk patients, they suggest TMP-SMX prophylaxis may be beneficial, especially given the high morbidity and mortality rates. For intermediate-risk patients, the researchers recommend a low threshold for prophylaxis; that is, any additional risk factor, such as prolonged use of corticosteroids, should prompt initiation of TMP-SMX. But for low-risk patients, they advise avoiding routine pneumocystosis prophylaxis.

Source
Fillatre P, Decaux O, Jouneau S, et al. Am J Med. 2014;127(12):1242.e11-1242.e17.
doi: 10.1016/j.amjmed.2014.07.010.

Pneumocystis jiroveci pneumonia is associated with high mortality rates in immunocompromised patients who are HIV-negative. In-hospital mortality rates range from 50% to 86%. Although trimethoprim-sulfamethoxazole (TMP-SMX) is an effective prophylaxis, the wide spectrum of immunosuppressive conditions predisposing to pneumocystosis and the limited data available on its incidence in non–HIV-infected patients has made it hard to establish an evidence-based guideline, say researchers from Hôpital Pontchaillou, Hôpital Sud, and Université Rennes 1, all in Rennes, France. The study is the first to offer comparative estimates of pneumocystosis incidence rates across this patient population and helps narrow down the patients at greatest risk.

The researchers retrospectively analyzed all cases of documented pneumocystosis in HIV-negative patients admitted to Rennes University Hospital between 1990 and 2010. Of 293 cases of pneumocystosis, 154 (52.6%) tested negative for HIV.

Related: NSAIDs Linked to Poor Pneumonia Outcomes

One of the study’s main findings was that pneumocystosis remains a significant problem in both HIV-positive and HIV-negative immunocompromised patients. Second, the researchers found pneumocystosis is more severe in HIV-negative patients compared with HIV-positive patients, with much higher rates of intensive care unit (ICU) admission and in-ICU mortality.

The risk of pneumocystosis was particularly high (> 45 cases per 100,000 patient-years) in 2 groups: patients with inflammatory diseases/vasculitis (polyarteritis nodosa, granulomatosis with polyangiitis, polymyositis/dermatopolymyositis) and 3 hematologic malignancies (acute leukemia, chronic lymphocytic leukemia, and non-Hodgkin lymphoma).

Related: Linezolid Contributes to "Clinical Success" in MRSA Pneumonia

They found intermediate risk (25-45 cases per 100,000 patient-years) for Waldenström macroglobulinemia, multiple myeloma, and central nervous system cancer. For those patients, the researchers recommend a low threshold for prophylaxis; that is, any additional risk factor, such as prolonged use of corticosteroids, should prompt initiation of TMP-SMX. Most patients with solid tumors and inflammatory diseases were at low risk (< 25 cases per 100,000 patient-years).

Their study findings can help guide more systematic use of TMP-SMX prophylaxis, the researchers say. For high-risk patients, they suggest TMP-SMX prophylaxis may be beneficial, especially given the high morbidity and mortality rates. For intermediate-risk patients, the researchers recommend a low threshold for prophylaxis; that is, any additional risk factor, such as prolonged use of corticosteroids, should prompt initiation of TMP-SMX. But for low-risk patients, they advise avoiding routine pneumocystosis prophylaxis.

Source
Fillatre P, Decaux O, Jouneau S, et al. Am J Med. 2014;127(12):1242.e11-1242.e17.
doi: 10.1016/j.amjmed.2014.07.010.

Endocrine therapy reduces the risk of recurrent breast cancer, but nonadherence is high. Researchers from Utrecht University, Leiden University Medical University, Diaconessenhuis Hospital, and the Netherlands Institute for Health Services Research, all in the Netherlands, felt there was more to nonadherence than most surveys were reporting. So they developed the Tailored Medicine Inventory, which allowed respondents to skip irrelevant items and expand on areas that are usually more limited, such as practical problems they encounter with the treatment.

The 241 survey respondents answered questions about their perceptions of the efficacy of endocrine therapy, worries about adverse effects (AEs), and practical problems that impact adherence, such as packaging, refills, and understanding information. The researchers also assessed perceived self-efficacy, using the Medication Use and Understanding Self-Efficacy scale. They used 2 scales to assess nonadherence: the Medication Adherence Rating Scale-5 and because that scale seemed to underrepresent unintentional nonadherence, they included the Morisky Medication Adherence Scale, with additional questions about forgetting to take the endocrine tablets and persistence.

Related: New Protocol Aims to Evaluate Medication Nonadherence

A substantial number of women were not convinced of the efficacy of endocrine therapy (30%). Some did not believe it was necessary (14%) or doubted its capacity to prevent cancer recurrence (32%). Nineteen percent of the women said they didn’t know how endocrine therapy works, and 20% said that they lacked information about it and didn’t know to what extent it reduced the chance of recurrence.

One hundred sixteen of the women surveyed (48%) experienced ≥ 1 practical problems, most often in the categories of information, intake of tablets, and packaging. All categories except “limitations in daily life” posed “substantial bother” to the women, the researchers say. Practical problems more than doubled the chance of unintentional nonadherence.

Related: Gene Expression Signatures in Breast Cancer: A Surgical Oncologist's Perspective

Self-reported unintentional nonadherence was high (85%), and intentional nonadherence or premature discontinuation was even higher (90%-92%). However, the researchers found no association between perceptions of the efficacy of endocrine therapy and nonadherence. Older women and those who were being treated for recurrent breast cancer were less likely to be unintentionally nonadherent. Perceived self-efficacy was associated with lower levels of both unintentional and intentional nonadherence.

The likelihood of intentional nonadherence rose by 20% for every additional AE experienced. Common AEs were a source of worry; particularly the best-known ones, such as hot flushes, reduced libido, cramps, joint ache, and joint stiffness. But the respondents often mentioned other AEs than those most often described in the literature. Memory and concentration problems, the researchers say, are consistent with AEs documented in the neuropsychologic side study of the Tamoxifen Exemestane Adjuvant Multinational trial. This finding, the researchers say, underscores the importance of not restricting assessment in clinical practice to only familiar AEs.

Related: Early Cancer Detection Helps Underserved Women

The researchers concluded with the acknowledgment that endocrine nonadherence is a complex and multifaceted issue in which women’s varied experiences are all factors. In short, one size does not fit all. Thus, they suggest—absent a unifying causal model—that a “promising approach” is to investigate a wide array of women’s experiences and perceptions. Targeting specific concerns and helping women boost self-efficacy could help drive up adherence.

Source
Wouters H, Stiggelbout AM, Bouvy ML, et al. Clin Breast Cancer. 2014;14(6):460-467e2.
doi: 10.1016/j.clbc.2014.04.005.

Endocrine therapy reduces the risk of recurrent breast cancer, but nonadherence is high. Researchers from Utrecht University, Leiden University Medical University, Diaconessenhuis Hospital, and the Netherlands Institute for Health Services Research, all in the Netherlands, felt there was more to nonadherence than most surveys were reporting. So they developed the Tailored Medicine Inventory, which allowed respondents to skip irrelevant items and expand on areas that are usually more limited, such as practical problems they encounter with the treatment.

The 241 survey respondents answered questions about their perceptions of the efficacy of endocrine therapy, worries about adverse effects (AEs), and practical problems that impact adherence, such as packaging, refills, and understanding information. The researchers also assessed perceived self-efficacy, using the Medication Use and Understanding Self-Efficacy scale. They used 2 scales to assess nonadherence: the Medication Adherence Rating Scale-5 and because that scale seemed to underrepresent unintentional nonadherence, they included the Morisky Medication Adherence Scale, with additional questions about forgetting to take the endocrine tablets and persistence.

Related: New Protocol Aims to Evaluate Medication Nonadherence

A substantial number of women were not convinced of the efficacy of endocrine therapy (30%). Some did not believe it was necessary (14%) or doubted its capacity to prevent cancer recurrence (32%). Nineteen percent of the women said they didn’t know how endocrine therapy works, and 20% said that they lacked information about it and didn’t know to what extent it reduced the chance of recurrence.

One hundred sixteen of the women surveyed (48%) experienced ≥ 1 practical problems, most often in the categories of information, intake of tablets, and packaging. All categories except “limitations in daily life” posed “substantial bother” to the women, the researchers say. Practical problems more than doubled the chance of unintentional nonadherence.

Related: Gene Expression Signatures in Breast Cancer: A Surgical Oncologist's Perspective

Self-reported unintentional nonadherence was high (85%), and intentional nonadherence or premature discontinuation was even higher (90%-92%). However, the researchers found no association between perceptions of the efficacy of endocrine therapy and nonadherence. Older women and those who were being treated for recurrent breast cancer were less likely to be unintentionally nonadherent. Perceived self-efficacy was associated with lower levels of both unintentional and intentional nonadherence.

The likelihood of intentional nonadherence rose by 20% for every additional AE experienced. Common AEs were a source of worry; particularly the best-known ones, such as hot flushes, reduced libido, cramps, joint ache, and joint stiffness. But the respondents often mentioned other AEs than those most often described in the literature. Memory and concentration problems, the researchers say, are consistent with AEs documented in the neuropsychologic side study of the Tamoxifen Exemestane Adjuvant Multinational trial. This finding, the researchers say, underscores the importance of not restricting assessment in clinical practice to only familiar AEs.

Related: Early Cancer Detection Helps Underserved Women

The researchers concluded with the acknowledgment that endocrine nonadherence is a complex and multifaceted issue in which women’s varied experiences are all factors. In short, one size does not fit all. Thus, they suggest—absent a unifying causal model—that a “promising approach” is to investigate a wide array of women’s experiences and perceptions. Targeting specific concerns and helping women boost self-efficacy could help drive up adherence.

Source
Wouters H, Stiggelbout AM, Bouvy ML, et al. Clin Breast Cancer. 2014;14(6):460-467e2.
doi: 10.1016/j.clbc.2014.04.005.

Endocrine therapy reduces the risk of recurrent breast cancer, but nonadherence is high. Researchers from Utrecht University, Leiden University Medical University, Diaconessenhuis Hospital, and the Netherlands Institute for Health Services Research, all in the Netherlands, felt there was more to nonadherence than most surveys were reporting. So they developed the Tailored Medicine Inventory, which allowed respondents to skip irrelevant items and expand on areas that are usually more limited, such as practical problems they encounter with the treatment.

The 241 survey respondents answered questions about their perceptions of the efficacy of endocrine therapy, worries about adverse effects (AEs), and practical problems that impact adherence, such as packaging, refills, and understanding information. The researchers also assessed perceived self-efficacy, using the Medication Use and Understanding Self-Efficacy scale. They used 2 scales to assess nonadherence: the Medication Adherence Rating Scale-5 and because that scale seemed to underrepresent unintentional nonadherence, they included the Morisky Medication Adherence Scale, with additional questions about forgetting to take the endocrine tablets and persistence.

Related: New Protocol Aims to Evaluate Medication Nonadherence

A substantial number of women were not convinced of the efficacy of endocrine therapy (30%). Some did not believe it was necessary (14%) or doubted its capacity to prevent cancer recurrence (32%). Nineteen percent of the women said they didn’t know how endocrine therapy works, and 20% said that they lacked information about it and didn’t know to what extent it reduced the chance of recurrence.

One hundred sixteen of the women surveyed (48%) experienced ≥ 1 practical problems, most often in the categories of information, intake of tablets, and packaging. All categories except “limitations in daily life” posed “substantial bother” to the women, the researchers say. Practical problems more than doubled the chance of unintentional nonadherence.

Related: Gene Expression Signatures in Breast Cancer: A Surgical Oncologist's Perspective

Self-reported unintentional nonadherence was high (85%), and intentional nonadherence or premature discontinuation was even higher (90%-92%). However, the researchers found no association between perceptions of the efficacy of endocrine therapy and nonadherence. Older women and those who were being treated for recurrent breast cancer were less likely to be unintentionally nonadherent. Perceived self-efficacy was associated with lower levels of both unintentional and intentional nonadherence.

The likelihood of intentional nonadherence rose by 20% for every additional AE experienced. Common AEs were a source of worry; particularly the best-known ones, such as hot flushes, reduced libido, cramps, joint ache, and joint stiffness. But the respondents often mentioned other AEs than those most often described in the literature. Memory and concentration problems, the researchers say, are consistent with AEs documented in the neuropsychologic side study of the Tamoxifen Exemestane Adjuvant Multinational trial. This finding, the researchers say, underscores the importance of not restricting assessment in clinical practice to only familiar AEs.

Related: Early Cancer Detection Helps Underserved Women

The researchers concluded with the acknowledgment that endocrine nonadherence is a complex and multifaceted issue in which women’s varied experiences are all factors. In short, one size does not fit all. Thus, they suggest—absent a unifying causal model—that a “promising approach” is to investigate a wide array of women’s experiences and perceptions. Targeting specific concerns and helping women boost self-efficacy could help drive up adherence.

Source
Wouters H, Stiggelbout AM, Bouvy ML, et al. Clin Breast Cancer. 2014;14(6):460-467e2.
doi: 10.1016/j.clbc.2014.04.005.

The FDA has approved the first combination pill to treat chronic hepatitis C virus (HCV) infection. This drug is also the first approved regimen that does not require administration with interferon or ribavirin.

The pill combines ledipasvir and sofosbuvir, 2 drugs that interfere with the enzymes HCV needs to multiply. Ledipasvir, a new drug, is an HCV NS5A inhibitor; sofosbuvir is an HCV nucleotide analog NS5B polymerase inhibitor.

Related: Viral Hepatitis Awareness

The recommended dose is 1 tablet taken once daily with or without food. The recommended treatment is 12 weeks for treatment-naïve patients with or without cirrhosis; 12 weeks for treatment-experienced patients (ie, those who have not responded to peginterferon alfa in combination with ribavirin or an HCV protease inhibitor combined with peginterferon alfa and ribavirin) without cirrhosis; and 24 weeks for treatment-experienced patients with cirrhosis. An 8-week treatment can be considered for treatment-naïve patients without cirrhosis who have pretreatment HCV RNA < 6 million IU/mL.

Related: Is Age-Based HCV Screening a Benefit?

The fixed-dose combination (ledipasvir 90 mg, sofosbuvir 400 mg) was evaluated in 3 clinical trials involving 1,518 patients who had not previously received treatment for their infection or who had not responded to previous treatment. Participants were randomly assigned to receive the combination pill with or without ribavirin. In the first trial of treatment-naïve patients, 202 of 215 patients (94%) who received ledipasvir-sofosbuvir for 8 weeks and 208 of 216 patients (96%) who received it for 12 weeks achieved sustained virologic response (SVR). In the second trial, 99% of patients with and without cirrhosis achieved SVR after 12 weeks.

The third trial evaluated efficacy in treatment-experienced participants with and without cirrhosis. In the 12-week arm, 102 of 109 patients (94%) achieved SVR, as did 108 of 109 patients (99%) in the 24-week arm. In all the trials, ribavirin did not increase response rates.

Related: Hepatitis C (Patient Information)

This is the seventh new drug designated as breakthrough therapy to receive FDA approval. It was reviewed under the priority review program, which expedites review of drugs that treat serious conditions and could significantly improve safety or effectiveness. 

Sources
FDA Hepatitis Update—Approval of Harvoni fixed-dose combination tablet (ledipasvir and sofosbuvir) for treatment of Hepatitis C. Silver Spring; MD: U.S. Food and Drug Administration; 2014.

FDA approves first combination pill to treat hepatitis C [news release]. Silver Spring, MD: U.S. Food and Drug Administration; October 10, 2014.

The FDA has approved the first combination pill to treat chronic hepatitis C virus (HCV) infection. This drug is also the first approved regimen that does not require administration with interferon or ribavirin.

The pill combines ledipasvir and sofosbuvir, 2 drugs that interfere with the enzymes HCV needs to multiply. Ledipasvir, a new drug, is an HCV NS5A inhibitor; sofosbuvir is an HCV nucleotide analog NS5B polymerase inhibitor.

Related: Viral Hepatitis Awareness

The recommended dose is 1 tablet taken once daily with or without food. The recommended treatment is 12 weeks for treatment-naïve patients with or without cirrhosis; 12 weeks for treatment-experienced patients (ie, those who have not responded to peginterferon alfa in combination with ribavirin or an HCV protease inhibitor combined with peginterferon alfa and ribavirin) without cirrhosis; and 24 weeks for treatment-experienced patients with cirrhosis. An 8-week treatment can be considered for treatment-naïve patients without cirrhosis who have pretreatment HCV RNA < 6 million IU/mL.

Related: Is Age-Based HCV Screening a Benefit?

The fixed-dose combination (ledipasvir 90 mg, sofosbuvir 400 mg) was evaluated in 3 clinical trials involving 1,518 patients who had not previously received treatment for their infection or who had not responded to previous treatment. Participants were randomly assigned to receive the combination pill with or without ribavirin. In the first trial of treatment-naïve patients, 202 of 215 patients (94%) who received ledipasvir-sofosbuvir for 8 weeks and 208 of 216 patients (96%) who received it for 12 weeks achieved sustained virologic response (SVR). In the second trial, 99% of patients with and without cirrhosis achieved SVR after 12 weeks.

The third trial evaluated efficacy in treatment-experienced participants with and without cirrhosis. In the 12-week arm, 102 of 109 patients (94%) achieved SVR, as did 108 of 109 patients (99%) in the 24-week arm. In all the trials, ribavirin did not increase response rates.

Related: Hepatitis C (Patient Information)

This is the seventh new drug designated as breakthrough therapy to receive FDA approval. It was reviewed under the priority review program, which expedites review of drugs that treat serious conditions and could significantly improve safety or effectiveness. 

Sources
FDA Hepatitis Update—Approval of Harvoni fixed-dose combination tablet (ledipasvir and sofosbuvir) for treatment of Hepatitis C. Silver Spring; MD: U.S. Food and Drug Administration; 2014.

FDA approves first combination pill to treat hepatitis C [news release]. Silver Spring, MD: U.S. Food and Drug Administration; October 10, 2014.

The FDA has approved the first combination pill to treat chronic hepatitis C virus (HCV) infection. This drug is also the first approved regimen that does not require administration with interferon or ribavirin.

The pill combines ledipasvir and sofosbuvir, 2 drugs that interfere with the enzymes HCV needs to multiply. Ledipasvir, a new drug, is an HCV NS5A inhibitor; sofosbuvir is an HCV nucleotide analog NS5B polymerase inhibitor.

Related: Viral Hepatitis Awareness

The recommended dose is 1 tablet taken once daily with or without food. The recommended treatment is 12 weeks for treatment-naïve patients with or without cirrhosis; 12 weeks for treatment-experienced patients (ie, those who have not responded to peginterferon alfa in combination with ribavirin or an HCV protease inhibitor combined with peginterferon alfa and ribavirin) without cirrhosis; and 24 weeks for treatment-experienced patients with cirrhosis. An 8-week treatment can be considered for treatment-naïve patients without cirrhosis who have pretreatment HCV RNA < 6 million IU/mL.

Related: Is Age-Based HCV Screening a Benefit?

The fixed-dose combination (ledipasvir 90 mg, sofosbuvir 400 mg) was evaluated in 3 clinical trials involving 1,518 patients who had not previously received treatment for their infection or who had not responded to previous treatment. Participants were randomly assigned to receive the combination pill with or without ribavirin. In the first trial of treatment-naïve patients, 202 of 215 patients (94%) who received ledipasvir-sofosbuvir for 8 weeks and 208 of 216 patients (96%) who received it for 12 weeks achieved sustained virologic response (SVR). In the second trial, 99% of patients with and without cirrhosis achieved SVR after 12 weeks.

The third trial evaluated efficacy in treatment-experienced participants with and without cirrhosis. In the 12-week arm, 102 of 109 patients (94%) achieved SVR, as did 108 of 109 patients (99%) in the 24-week arm. In all the trials, ribavirin did not increase response rates.

Related: Hepatitis C (Patient Information)

This is the seventh new drug designated as breakthrough therapy to receive FDA approval. It was reviewed under the priority review program, which expedites review of drugs that treat serious conditions and could significantly improve safety or effectiveness. 

Sources
FDA Hepatitis Update—Approval of Harvoni fixed-dose combination tablet (ledipasvir and sofosbuvir) for treatment of Hepatitis C. Silver Spring; MD: U.S. Food and Drug Administration; 2014.

FDA approves first combination pill to treat hepatitis C [news release]. Silver Spring, MD: U.S. Food and Drug Administration; October 10, 2014.

Lhermitte sign, a neuropathic symptom commonly associated with multiple sclerosis, may also be an adverse effect (AE) of oxaliplatin therapy, according to a case report by clinicians from Western Michigan University School of Medicine, Bronson Methodist Hospital, and West Michigan Cancer Center, all in Kalamazoo, Michigan.

Their patient, a Hispanic man aged 50 years with locally advanced colorectal cancer, underwent a laparoscopic low anterior resection, with end-to-end anastomosis. His tumor was stage 3. Because he had a busy work schedule, his physicians decided to treat him with capecitabine and oxaliplatin (CAPEOX), rather than the treatment recommended by the National Comprehensive Cancer Network guidelines of 6 months of adjuvant chemotherapy with 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX). The FOLFOX regimen uses 85 mg/m² of oxaliplatin every 2 weeks. The CAPEOX regimen uses 130 mg/m² of oxaliplatin every 3 weeks.

Related: The Best Times to Try Abiraterone

After 7 cycles of chemotherapy, the patient developed severe electric shocklike pain that shot down his back and extremities when he bent his neck. He also had a slight tingling and numbness in his upper arms and fingertips. A thorough history and physical examination revealed a classic Lhermitte sign on neck flexion with no other significant findings. The oxaliplatin was discontinued, and he was switched to capecitabine to complete 6 months of adjuvant chemotherapy.

Six months after the oxaliplatin was stopped, his symptoms resolved. A repeat computed tomography scan and 1-year follow-up colonoscopy did not reveal any evidence for recurrent colorectal cancer.

Related: Efficacy of the Colonoscopy Outsourcing Systems Used at a Large VA Medical Center

Lhermitte phenomenon due to chemotherapy is rare, the authors say, although polyneuropathy is a common AE of oxaliplatin at higher doses. The onset of Lhermitte sign can be delayed by weeks to months. The usual cause is cisplatin or oxaliplatin, but it has also been implicated in regimens that include docetaxel, cyclophosphamide, and fludarabine. The cumulative dose in affected patients has ranged from 574 mg to 2,040 mg (this patient had a cumulative dose of 830 mg/m²).

The fact that their patient received a lower cumulative dose than in the other reported cases led his clinicians to believe that there might be an additional mechanism at work in his case, such as greater interval dosing (130 mg/m²) and/or coadministration with capecitabine. A literature review revealed that the case is the first report of Lhermitte sign induced by oxaliplatin in combination with capecitabine in a Hispanic patient with colorectal cancer, concurrently being treated with capecitabine.

They say it isn’t clear, though, whether capecitabine could have a role in causing or potentiating Lhermitte sign. But because capecitabine is being used more often instead of 5-fluorouracil with oxaliplatin in colorectal cancer, the researchers caution that neurologic AEs could happen more frequently. Interestingly, although the authors found reported cases of Lhermitte sign with oxaliplatin, they note that no clinical trials have reported it as an AE of oxaliplatin.

Lhermitte sign, though it can be debilitating, seems to be almost fully reversible, the authors say, with few, if any, residual paresthesias.

Source
Amaraneni A, Seth A, Itawi EA, Chandana SR. Clin Colorectal Cancer. 2014:13(4):257-259.
doi: 10.1016/j.clcc.2014.09.006.

Lhermitte sign, a neuropathic symptom commonly associated with multiple sclerosis, may also be an adverse effect (AE) of oxaliplatin therapy, according to a case report by clinicians from Western Michigan University School of Medicine, Bronson Methodist Hospital, and West Michigan Cancer Center, all in Kalamazoo, Michigan.

Their patient, a Hispanic man aged 50 years with locally advanced colorectal cancer, underwent a laparoscopic low anterior resection, with end-to-end anastomosis. His tumor was stage 3. Because he had a busy work schedule, his physicians decided to treat him with capecitabine and oxaliplatin (CAPEOX), rather than the treatment recommended by the National Comprehensive Cancer Network guidelines of 6 months of adjuvant chemotherapy with 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX). The FOLFOX regimen uses 85 mg/m² of oxaliplatin every 2 weeks. The CAPEOX regimen uses 130 mg/m² of oxaliplatin every 3 weeks.

Related: The Best Times to Try Abiraterone

After 7 cycles of chemotherapy, the patient developed severe electric shocklike pain that shot down his back and extremities when he bent his neck. He also had a slight tingling and numbness in his upper arms and fingertips. A thorough history and physical examination revealed a classic Lhermitte sign on neck flexion with no other significant findings. The oxaliplatin was discontinued, and he was switched to capecitabine to complete 6 months of adjuvant chemotherapy.

Six months after the oxaliplatin was stopped, his symptoms resolved. A repeat computed tomography scan and 1-year follow-up colonoscopy did not reveal any evidence for recurrent colorectal cancer.

Related: Efficacy of the Colonoscopy Outsourcing Systems Used at a Large VA Medical Center

Lhermitte phenomenon due to chemotherapy is rare, the authors say, although polyneuropathy is a common AE of oxaliplatin at higher doses. The onset of Lhermitte sign can be delayed by weeks to months. The usual cause is cisplatin or oxaliplatin, but it has also been implicated in regimens that include docetaxel, cyclophosphamide, and fludarabine. The cumulative dose in affected patients has ranged from 574 mg to 2,040 mg (this patient had a cumulative dose of 830 mg/m²).

The fact that their patient received a lower cumulative dose than in the other reported cases led his clinicians to believe that there might be an additional mechanism at work in his case, such as greater interval dosing (130 mg/m²) and/or coadministration with capecitabine. A literature review revealed that the case is the first report of Lhermitte sign induced by oxaliplatin in combination with capecitabine in a Hispanic patient with colorectal cancer, concurrently being treated with capecitabine.

They say it isn’t clear, though, whether capecitabine could have a role in causing or potentiating Lhermitte sign. But because capecitabine is being used more often instead of 5-fluorouracil with oxaliplatin in colorectal cancer, the researchers caution that neurologic AEs could happen more frequently. Interestingly, although the authors found reported cases of Lhermitte sign with oxaliplatin, they note that no clinical trials have reported it as an AE of oxaliplatin.

Lhermitte sign, though it can be debilitating, seems to be almost fully reversible, the authors say, with few, if any, residual paresthesias.

Source
Amaraneni A, Seth A, Itawi EA, Chandana SR. Clin Colorectal Cancer. 2014:13(4):257-259.
doi: 10.1016/j.clcc.2014.09.006.

Lhermitte sign, a neuropathic symptom commonly associated with multiple sclerosis, may also be an adverse effect (AE) of oxaliplatin therapy, according to a case report by clinicians from Western Michigan University School of Medicine, Bronson Methodist Hospital, and West Michigan Cancer Center, all in Kalamazoo, Michigan.

Their patient, a Hispanic man aged 50 years with locally advanced colorectal cancer, underwent a laparoscopic low anterior resection, with end-to-end anastomosis. His tumor was stage 3. Because he had a busy work schedule, his physicians decided to treat him with capecitabine and oxaliplatin (CAPEOX), rather than the treatment recommended by the National Comprehensive Cancer Network guidelines of 6 months of adjuvant chemotherapy with 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX). The FOLFOX regimen uses 85 mg/m² of oxaliplatin every 2 weeks. The CAPEOX regimen uses 130 mg/m² of oxaliplatin every 3 weeks.

Related: The Best Times to Try Abiraterone

After 7 cycles of chemotherapy, the patient developed severe electric shocklike pain that shot down his back and extremities when he bent his neck. He also had a slight tingling and numbness in his upper arms and fingertips. A thorough history and physical examination revealed a classic Lhermitte sign on neck flexion with no other significant findings. The oxaliplatin was discontinued, and he was switched to capecitabine to complete 6 months of adjuvant chemotherapy.

Six months after the oxaliplatin was stopped, his symptoms resolved. A repeat computed tomography scan and 1-year follow-up colonoscopy did not reveal any evidence for recurrent colorectal cancer.

Related: Efficacy of the Colonoscopy Outsourcing Systems Used at a Large VA Medical Center

Lhermitte phenomenon due to chemotherapy is rare, the authors say, although polyneuropathy is a common AE of oxaliplatin at higher doses. The onset of Lhermitte sign can be delayed by weeks to months. The usual cause is cisplatin or oxaliplatin, but it has also been implicated in regimens that include docetaxel, cyclophosphamide, and fludarabine. The cumulative dose in affected patients has ranged from 574 mg to 2,040 mg (this patient had a cumulative dose of 830 mg/m²).

The fact that their patient received a lower cumulative dose than in the other reported cases led his clinicians to believe that there might be an additional mechanism at work in his case, such as greater interval dosing (130 mg/m²) and/or coadministration with capecitabine. A literature review revealed that the case is the first report of Lhermitte sign induced by oxaliplatin in combination with capecitabine in a Hispanic patient with colorectal cancer, concurrently being treated with capecitabine.

They say it isn’t clear, though, whether capecitabine could have a role in causing or potentiating Lhermitte sign. But because capecitabine is being used more often instead of 5-fluorouracil with oxaliplatin in colorectal cancer, the researchers caution that neurologic AEs could happen more frequently. Interestingly, although the authors found reported cases of Lhermitte sign with oxaliplatin, they note that no clinical trials have reported it as an AE of oxaliplatin.

Lhermitte sign, though it can be debilitating, seems to be almost fully reversible, the authors say, with few, if any, residual paresthesias.

Source
Amaraneni A, Seth A, Itawi EA, Chandana SR. Clin Colorectal Cancer. 2014:13(4):257-259.
doi: 10.1016/j.clcc.2014.09.006.

The public tends to think of antibiotic resistance as a problem that largely affects patients in hospitals, say researchers from Cardiff University, University of Oxford, and Pharmatelligence, all in the United Kingdom (UK); and Abbott Healthcare Products in the Netherlands. Unfortunately, they note, so do many primary care practitioners, even though recent antibiotic use in primary care is the single most important risk factor for an infection with a resistant organism.

As the researchers’ study of 22 years of primary care prescribing in the UK makes clear, antibiotic resistance is a primary care problem, too. During that time, > 1 in 10 of the initial antibiotic monotherapies they studied failed.

Using data on 58 million antibiotic prescriptions from the Clinical Practice Research Datalink, a database derived from nearly 700 primary care practices in the UK, the researchers analyzed almost 11 million first-time monotherapy episodes for 4 indications: upper respiratory tract infections (URTIs), lower respiratory tract infections, skin and soft tissue infections, and acute otitis media. Of all antibiotic prescriptions, 98% were monotherapy.

Over time, the proportion of infections treated with antibiotics changed. The greatest increase was in the smallest class, acute otitis media, which rose from 63% in 1991 to 83% in 2012. The proportion of URTIs treated with antibiotics dropped from 59% in 1991 to 55% in 2012.

The most commonly prescribed antibiotics were amoxicillin (42% of infections), followed by phenoxymethylpenicillin (penicillin-V) (95% for URTIs) and flucloxacillin (97% for skin and soft tissue infections).

The treatment failure rate rose from 13.9% in 1991 to 15.4% in 2012, with some “notably high levels of failure,” the researchers say. They cite trimethoprim’s overall failure rate of 37% (increasing from 24.7% in 1991 to 55.9% in 2012) when used to treat URTIs. Failure rates for cephalosporins also increased “markedly.” By contrast, failure rates for macrolides across the 4 infection classes remained largely stable. In 2012, the antibiotics with the lowest failure rates were penicillin-V for URTIs, and lymecycline and oxytetracycline for skin and soft tissue infections.

The rise in antibiotic failures was less prominent for the most frequently prescribed antibiotics and those recommended for first-line treatment, such as amoxicillin, clarithromycin, and erythromycin. The more striking increases were seen in antibiotics not usually recommended as first-line treatments for the infection classes in the study, such as cephalosporins. Those drugs, however, might have been prescribed for more severely ill and frail patients who had recently been prescribed a first-line drug or who were already resistant to a drug, the researchers say.

Most of the increase in failures dated from 2000, the researchers say, when community antibiotic prescribing, which had been falling in the late 1990s, plateaued, and then once again began rising.

Their findings could represent a phenomenon that will resolve, or might be an “early indication of a more dramatic and worrying process,” the researchers caution. The finding that 1 in 10 initial antibiotic treatments in primary care fails represents a “considerable burden” on patients and the health care system. They suggest that primary care physicians can play a central role in helping to contain rises in antibiotic treatment failures by managing patient expectations and carefully considering whether each prescription is justified.

Source
Currie CJ, Berni E, Jenkins-Jones S, et al. BMJ. 2014;349:g5493.
doi: 10.1136/bmj.g5493.

The public tends to think of antibiotic resistance as a problem that largely affects patients in hospitals, say researchers from Cardiff University, University of Oxford, and Pharmatelligence, all in the United Kingdom (UK); and Abbott Healthcare Products in the Netherlands. Unfortunately, they note, so do many primary care practitioners, even though recent antibiotic use in primary care is the single most important risk factor for an infection with a resistant organism.

As the researchers’ study of 22 years of primary care prescribing in the UK makes clear, antibiotic resistance is a primary care problem, too. During that time, > 1 in 10 of the initial antibiotic monotherapies they studied failed.

Using data on 58 million antibiotic prescriptions from the Clinical Practice Research Datalink, a database derived from nearly 700 primary care practices in the UK, the researchers analyzed almost 11 million first-time monotherapy episodes for 4 indications: upper respiratory tract infections (URTIs), lower respiratory tract infections, skin and soft tissue infections, and acute otitis media. Of all antibiotic prescriptions, 98% were monotherapy.

Over time, the proportion of infections treated with antibiotics changed. The greatest increase was in the smallest class, acute otitis media, which rose from 63% in 1991 to 83% in 2012. The proportion of URTIs treated with antibiotics dropped from 59% in 1991 to 55% in 2012.

The most commonly prescribed antibiotics were amoxicillin (42% of infections), followed by phenoxymethylpenicillin (penicillin-V) (95% for URTIs) and flucloxacillin (97% for skin and soft tissue infections).

The treatment failure rate rose from 13.9% in 1991 to 15.4% in 2012, with some “notably high levels of failure,” the researchers say. They cite trimethoprim’s overall failure rate of 37% (increasing from 24.7% in 1991 to 55.9% in 2012) when used to treat URTIs. Failure rates for cephalosporins also increased “markedly.” By contrast, failure rates for macrolides across the 4 infection classes remained largely stable. In 2012, the antibiotics with the lowest failure rates were penicillin-V for URTIs, and lymecycline and oxytetracycline for skin and soft tissue infections.

The rise in antibiotic failures was less prominent for the most frequently prescribed antibiotics and those recommended for first-line treatment, such as amoxicillin, clarithromycin, and erythromycin. The more striking increases were seen in antibiotics not usually recommended as first-line treatments for the infection classes in the study, such as cephalosporins. Those drugs, however, might have been prescribed for more severely ill and frail patients who had recently been prescribed a first-line drug or who were already resistant to a drug, the researchers say.

Most of the increase in failures dated from 2000, the researchers say, when community antibiotic prescribing, which had been falling in the late 1990s, plateaued, and then once again began rising.

Their findings could represent a phenomenon that will resolve, or might be an “early indication of a more dramatic and worrying process,” the researchers caution. The finding that 1 in 10 initial antibiotic treatments in primary care fails represents a “considerable burden” on patients and the health care system. They suggest that primary care physicians can play a central role in helping to contain rises in antibiotic treatment failures by managing patient expectations and carefully considering whether each prescription is justified.

Source
Currie CJ, Berni E, Jenkins-Jones S, et al. BMJ. 2014;349:g5493.
doi: 10.1136/bmj.g5493.

The public tends to think of antibiotic resistance as a problem that largely affects patients in hospitals, say researchers from Cardiff University, University of Oxford, and Pharmatelligence, all in the United Kingdom (UK); and Abbott Healthcare Products in the Netherlands. Unfortunately, they note, so do many primary care practitioners, even though recent antibiotic use in primary care is the single most important risk factor for an infection with a resistant organism.

As the researchers’ study of 22 years of primary care prescribing in the UK makes clear, antibiotic resistance is a primary care problem, too. During that time, > 1 in 10 of the initial antibiotic monotherapies they studied failed.

Using data on 58 million antibiotic prescriptions from the Clinical Practice Research Datalink, a database derived from nearly 700 primary care practices in the UK, the researchers analyzed almost 11 million first-time monotherapy episodes for 4 indications: upper respiratory tract infections (URTIs), lower respiratory tract infections, skin and soft tissue infections, and acute otitis media. Of all antibiotic prescriptions, 98% were monotherapy.

Over time, the proportion of infections treated with antibiotics changed. The greatest increase was in the smallest class, acute otitis media, which rose from 63% in 1991 to 83% in 2012. The proportion of URTIs treated with antibiotics dropped from 59% in 1991 to 55% in 2012.

The most commonly prescribed antibiotics were amoxicillin (42% of infections), followed by phenoxymethylpenicillin (penicillin-V) (95% for URTIs) and flucloxacillin (97% for skin and soft tissue infections).

The treatment failure rate rose from 13.9% in 1991 to 15.4% in 2012, with some “notably high levels of failure,” the researchers say. They cite trimethoprim’s overall failure rate of 37% (increasing from 24.7% in 1991 to 55.9% in 2012) when used to treat URTIs. Failure rates for cephalosporins also increased “markedly.” By contrast, failure rates for macrolides across the 4 infection classes remained largely stable. In 2012, the antibiotics with the lowest failure rates were penicillin-V for URTIs, and lymecycline and oxytetracycline for skin and soft tissue infections.

The rise in antibiotic failures was less prominent for the most frequently prescribed antibiotics and those recommended for first-line treatment, such as amoxicillin, clarithromycin, and erythromycin. The more striking increases were seen in antibiotics not usually recommended as first-line treatments for the infection classes in the study, such as cephalosporins. Those drugs, however, might have been prescribed for more severely ill and frail patients who had recently been prescribed a first-line drug or who were already resistant to a drug, the researchers say.

Most of the increase in failures dated from 2000, the researchers say, when community antibiotic prescribing, which had been falling in the late 1990s, plateaued, and then once again began rising.

Their findings could represent a phenomenon that will resolve, or might be an “early indication of a more dramatic and worrying process,” the researchers caution. The finding that 1 in 10 initial antibiotic treatments in primary care fails represents a “considerable burden” on patients and the health care system. They suggest that primary care physicians can play a central role in helping to contain rises in antibiotic treatment failures by managing patient expectations and carefully considering whether each prescription is justified.

Source
Currie CJ, Berni E, Jenkins-Jones S, et al. BMJ. 2014;349:g5493.
doi: 10.1136/bmj.g5493.

The microbial cause of infection is often not known at the time antibiotics are prescribed for patients in Candida-related septic shock, but delaying therapy has been associated with a mortality rate of > 90%. Researchers from St. Louis College of Pharmacy, Barnes-Jewish Hospital, BJC HealthCare, and Washington University, all in St. Louis, Missouri, conducted a pilot study that found empiric antifungal treatment could shorten the time to administration of appropriate treatment for Candida-related septic shock.

The Barnes-Jewish Hospital intensive care unit (ICU) averages 1,400 admissions per year, the researchers say, with a 10% prevalence of Candida as the cause of septic shock. They add that the rate of resistance to fluconazole in all species of Candida combined is about 15%. In this before-after study, 15 patients who presented before December 31, 2012, were in the standard-care group. They received antibiotics, including antifungal drugs, at the discretion of the treating physician. The remaining 13 (treated after January 1, 2013) received empiric therapy with micafungin 100 mg/d or fluconazole 800 mg IV on day 1, followed by 400 mg/d IV. The choice of antifungal agent was left to the ICU team and clinical pharmacist but was partly based on whether the patient had any prior exposure to fluconazole, in which case micafungin was prescribed.

Sixteen patients received appropriate antifungal therapy. The remaining 12 patients received delayed antifungal therapy, 1 of which received no antifungal therapy before death.

The mean time from onset of shock to appropriate therapy was statistically shorter in the empiric therapy group (10.6 hours vs 40.5 hours). The mean time from culture collection to appropriate therapy was also statistically shorter in the empiric therapy group (13.7 hours vs 43.3 hours in the standard care group; P = .001). Patients who received empiric therapy were more likely to have received appropriate therapy within 12 hours (69.2% vs 6.7%) and within 24 hours (76.9% vs 40%).

 The shorter time to appropriate treatment meant a slight but noticeable difference in survival. Twelve patients died during hospitalization, but those who received appropriate therapy within 24 hours of onset of hypotension had greater hospital survival rates: 68.8% vs 41.7%.

Source
Micek ST, Arnold H, Juang P, et al. Clin Ther. 2014;36(9):1226-1232.
doi: 10.1016/j.clinthera.2014.06.28.

The microbial cause of infection is often not known at the time antibiotics are prescribed for patients in Candida-related septic shock, but delaying therapy has been associated with a mortality rate of > 90%. Researchers from St. Louis College of Pharmacy, Barnes-Jewish Hospital, BJC HealthCare, and Washington University, all in St. Louis, Missouri, conducted a pilot study that found empiric antifungal treatment could shorten the time to administration of appropriate treatment for Candida-related septic shock.

The Barnes-Jewish Hospital intensive care unit (ICU) averages 1,400 admissions per year, the researchers say, with a 10% prevalence of Candida as the cause of septic shock. They add that the rate of resistance to fluconazole in all species of Candida combined is about 15%. In this before-after study, 15 patients who presented before December 31, 2012, were in the standard-care group. They received antibiotics, including antifungal drugs, at the discretion of the treating physician. The remaining 13 (treated after January 1, 2013) received empiric therapy with micafungin 100 mg/d or fluconazole 800 mg IV on day 1, followed by 400 mg/d IV. The choice of antifungal agent was left to the ICU team and clinical pharmacist but was partly based on whether the patient had any prior exposure to fluconazole, in which case micafungin was prescribed.

Sixteen patients received appropriate antifungal therapy. The remaining 12 patients received delayed antifungal therapy, 1 of which received no antifungal therapy before death.

The mean time from onset of shock to appropriate therapy was statistically shorter in the empiric therapy group (10.6 hours vs 40.5 hours). The mean time from culture collection to appropriate therapy was also statistically shorter in the empiric therapy group (13.7 hours vs 43.3 hours in the standard care group; P = .001). Patients who received empiric therapy were more likely to have received appropriate therapy within 12 hours (69.2% vs 6.7%) and within 24 hours (76.9% vs 40%).

 The shorter time to appropriate treatment meant a slight but noticeable difference in survival. Twelve patients died during hospitalization, but those who received appropriate therapy within 24 hours of onset of hypotension had greater hospital survival rates: 68.8% vs 41.7%.

Source
Micek ST, Arnold H, Juang P, et al. Clin Ther. 2014;36(9):1226-1232.
doi: 10.1016/j.clinthera.2014.06.28.

The microbial cause of infection is often not known at the time antibiotics are prescribed for patients in Candida-related septic shock, but delaying therapy has been associated with a mortality rate of > 90%. Researchers from St. Louis College of Pharmacy, Barnes-Jewish Hospital, BJC HealthCare, and Washington University, all in St. Louis, Missouri, conducted a pilot study that found empiric antifungal treatment could shorten the time to administration of appropriate treatment for Candida-related septic shock.

The Barnes-Jewish Hospital intensive care unit (ICU) averages 1,400 admissions per year, the researchers say, with a 10% prevalence of Candida as the cause of septic shock. They add that the rate of resistance to fluconazole in all species of Candida combined is about 15%. In this before-after study, 15 patients who presented before December 31, 2012, were in the standard-care group. They received antibiotics, including antifungal drugs, at the discretion of the treating physician. The remaining 13 (treated after January 1, 2013) received empiric therapy with micafungin 100 mg/d or fluconazole 800 mg IV on day 1, followed by 400 mg/d IV. The choice of antifungal agent was left to the ICU team and clinical pharmacist but was partly based on whether the patient had any prior exposure to fluconazole, in which case micafungin was prescribed.

Sixteen patients received appropriate antifungal therapy. The remaining 12 patients received delayed antifungal therapy, 1 of which received no antifungal therapy before death.

The mean time from onset of shock to appropriate therapy was statistically shorter in the empiric therapy group (10.6 hours vs 40.5 hours). The mean time from culture collection to appropriate therapy was also statistically shorter in the empiric therapy group (13.7 hours vs 43.3 hours in the standard care group; P = .001). Patients who received empiric therapy were more likely to have received appropriate therapy within 12 hours (69.2% vs 6.7%) and within 24 hours (76.9% vs 40%).

 The shorter time to appropriate treatment meant a slight but noticeable difference in survival. Twelve patients died during hospitalization, but those who received appropriate therapy within 24 hours of onset of hypotension had greater hospital survival rates: 68.8% vs 41.7%.

Source
Micek ST, Arnold H, Juang P, et al. Clin Ther. 2014;36(9):1226-1232.
doi: 10.1016/j.clinthera.2014.06.28.