Pharmacology

Staphylococcus aureus (S aureus) is a common cause of infection within the hospital and in the community.¹ Treatment is based on the organism’s susceptibility to methicillin and is referred to as either MRSA (methicillin-resistant S aureus) or MSSA (methicillin-susceptible 
S aureus). As antibiotic resistance has evolved, patients with S aureus (especially MRSA) infections have become more difficult to treat. Susceptibility testing guides treatment of these infections and determines the minimum inhibitory concentration (MIC) for each antibiotic. A MIC is the minimum concentration of an antibiotic that will inhibit the visible growth of the organism after incubation.

Related: Experts Debate Infection Control Merits of ‘Bare Beneath the Elbows’

Vancomycin has remained the mainstay for treatment of patients with MRSA infections. An increasing number of infections with high documented MICs to vancomycin are raising concern that resistance may be developing. Clinical controversy exists within the infectious disease community as to whether vancomycin is less effective against S aureus infections with a vancomycin MIC of ≥ 2 µg/mL, contributing to poor patient outcomes.²

The Clinical and Laboratory Standards Institute (CLSI) lowered the breakpoint for vancomycin in 2006 from > 4 µg/mL to > 2 µg/mL.³ Breakpoints delineate MIC values that are considered susceptible, nonsusceptible, or resistant to an antibiotic. The CLSI breakpoint change points to an increase in vancomycin resistance and supports the need for further discussion and insight.

A 2012 meta-analysis was conducted to determine whether an association exists between S aureus infections with vancomycin MIC values ≥ 2 µg/mL and the effectiveness of the therapy.² Twenty-two studies were included with a primary outcome of 30-day mortality. A review of MRSA data revealed a statistically significant association between high vancomycin MICs (≥ 1.5 µg/mL) and increased mortality (P < .01), regardless of the source of infection. When limiting the data to Etest (bioMérieux, Marcy L’Etoile, France) MIC testing for MRSA bloodstream infections (BSIs), a vancomycin MIC ≥ 1.5 µg/mL was not associated with increased mortality (P = .08). Comparing data for MIC ≥ 2 µg/mL and ≤ 1.5 µg/mL, found that MICs ≥ 2 µg/mL were associated with increased mortality (P < .01). Analysis of the 11 studies that included data on treatment failure concluded that S aureus infections with a vancomycin MIC ≥ 1.5 µg/mL were associated with an increased risk of treatment failure in both MSSA and MRSA infections (P < .01) and that treatment failure was more likely in MRSA BSIs than in non-BSIs (P < .01).Evidence to support a possible correlation between high S aureus vancomycin MICs and poor patient outcomes came from a 2013 meta-analysis.³ The specific aim of this study was to examine the correlations between vancomycin MIC, patient mortality, and treatment failure. A MIC ≥ 1.5 µg/mL and ≥ 1.0 µg/mL were used to classify MICs as high when determined by Etest and broth microdilution (BMD), respectively. Analysis revealed an association between high vancomycin MICs and increased risk of treatment failure (relative risk [RR] 1.40, 95% confidence interval [CI] 1.15-1.71) and overall mortality (RR 1.42, 95% CI 1.08-1.87). Similarly, a sensitivity analysis on S aureus BSIs with high vancomycin MICs revealed an increased risk of mortality (RR 1.46, 95% CI 1.06-2.01) and treatment failure (RR 1.37, 95% CI 1.09-1.73).

Related: The Importance of an Antimicrobial Stewardship Program

The most recent meta-analysis (published in 2014) included patients with S aureus bacteremia and evaluated the association of high S aureus vancomycin MIC with an increased risk of mortality.⁴ A high MIC was defined as ≥ 1.5 µg/mL by Etest and ≥ 2.0 µg/mL by BMD. The analysis of 38 studies found a nonstatistically significant difference in mortality risk (P = .43). Further analysis was performed to determine whether the vancomycin MIC cutoff plays a role in increased mortality. No statistically significant difference in mortality was found when using a vancomycin MIC ≥ 1.5 µg/mL, ≥ 2.0 µg/mL, ≥ 4.0 µg/mL, or ≥ 8.0 µg/mL. The authors argued that their differing conclusions from other meta-analyses may be due to the inclusion of only bacteremias rather than all infection types, and although there was not a statistically significant difference, increased risk of mortality could not be excluded.

Related: Results Mixed in Hospital Efforts to Tackle Antimicrobial Resistance

Although conclusions of published meta-analyses differ, the results highlight the necessity of using clinical judgment in treating patients with S aureus infections with high MIC values and to consider the primary source and severity of infection. A confounding factor to direct comparison of the literature is the variations based on the method of MIC determination and testing (Etest vs BMD).

Additionally, all 3 studies addressed the importance of considering clinical patient factors that may lead to poorer prognosis as well as the difficultly in achieving necessary vancomycin levels with limited toxicity. The risk of increased mortality in patients with high vancomycin MICs cannot be ruled out at this time. Therefore, additional patient factors as well as the potential toxicities that may result from vancomycin therapy should be considered when using vancomycin in treating patients with S aureus infections.

Additional Note
An earlier version of this article appeared in the Pharmacy Related Newsletter: The Capsule, of the William S. Middleton Memorial Veterans Hospital.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

Staphylococcus aureus (S aureus) is a common cause of infection within the hospital and in the community.¹ Treatment is based on the organism’s susceptibility to methicillin and is referred to as either MRSA (methicillin-resistant S aureus) or MSSA (methicillin-susceptible 
S aureus). As antibiotic resistance has evolved, patients with S aureus (especially MRSA) infections have become more difficult to treat. Susceptibility testing guides treatment of these infections and determines the minimum inhibitory concentration (MIC) for each antibiotic. A MIC is the minimum concentration of an antibiotic that will inhibit the visible growth of the organism after incubation.

Related: Experts Debate Infection Control Merits of ‘Bare Beneath the Elbows’

Vancomycin has remained the mainstay for treatment of patients with MRSA infections. An increasing number of infections with high documented MICs to vancomycin are raising concern that resistance may be developing. Clinical controversy exists within the infectious disease community as to whether vancomycin is less effective against S aureus infections with a vancomycin MIC of ≥ 2 µg/mL, contributing to poor patient outcomes.²

The Clinical and Laboratory Standards Institute (CLSI) lowered the breakpoint for vancomycin in 2006 from > 4 µg/mL to > 2 µg/mL.³ Breakpoints delineate MIC values that are considered susceptible, nonsusceptible, or resistant to an antibiotic. The CLSI breakpoint change points to an increase in vancomycin resistance and supports the need for further discussion and insight.

A 2012 meta-analysis was conducted to determine whether an association exists between S aureus infections with vancomycin MIC values ≥ 2 µg/mL and the effectiveness of the therapy.² Twenty-two studies were included with a primary outcome of 30-day mortality. A review of MRSA data revealed a statistically significant association between high vancomycin MICs (≥ 1.5 µg/mL) and increased mortality (P < .01), regardless of the source of infection. When limiting the data to Etest (bioMérieux, Marcy L’Etoile, France) MIC testing for MRSA bloodstream infections (BSIs), a vancomycin MIC ≥ 1.5 µg/mL was not associated with increased mortality (P = .08). Comparing data for MIC ≥ 2 µg/mL and ≤ 1.5 µg/mL, found that MICs ≥ 2 µg/mL were associated with increased mortality (P < .01). Analysis of the 11 studies that included data on treatment failure concluded that S aureus infections with a vancomycin MIC ≥ 1.5 µg/mL were associated with an increased risk of treatment failure in both MSSA and MRSA infections (P < .01) and that treatment failure was more likely in MRSA BSIs than in non-BSIs (P < .01).Evidence to support a possible correlation between high S aureus vancomycin MICs and poor patient outcomes came from a 2013 meta-analysis.³ The specific aim of this study was to examine the correlations between vancomycin MIC, patient mortality, and treatment failure. A MIC ≥ 1.5 µg/mL and ≥ 1.0 µg/mL were used to classify MICs as high when determined by Etest and broth microdilution (BMD), respectively. Analysis revealed an association between high vancomycin MICs and increased risk of treatment failure (relative risk [RR] 1.40, 95% confidence interval [CI] 1.15-1.71) and overall mortality (RR 1.42, 95% CI 1.08-1.87). Similarly, a sensitivity analysis on S aureus BSIs with high vancomycin MICs revealed an increased risk of mortality (RR 1.46, 95% CI 1.06-2.01) and treatment failure (RR 1.37, 95% CI 1.09-1.73).

Related: The Importance of an Antimicrobial Stewardship Program

The most recent meta-analysis (published in 2014) included patients with S aureus bacteremia and evaluated the association of high S aureus vancomycin MIC with an increased risk of mortality.⁴ A high MIC was defined as ≥ 1.5 µg/mL by Etest and ≥ 2.0 µg/mL by BMD. The analysis of 38 studies found a nonstatistically significant difference in mortality risk (P = .43). Further analysis was performed to determine whether the vancomycin MIC cutoff plays a role in increased mortality. No statistically significant difference in mortality was found when using a vancomycin MIC ≥ 1.5 µg/mL, ≥ 2.0 µg/mL, ≥ 4.0 µg/mL, or ≥ 8.0 µg/mL. The authors argued that their differing conclusions from other meta-analyses may be due to the inclusion of only bacteremias rather than all infection types, and although there was not a statistically significant difference, increased risk of mortality could not be excluded.

Related: Results Mixed in Hospital Efforts to Tackle Antimicrobial Resistance

Although conclusions of published meta-analyses differ, the results highlight the necessity of using clinical judgment in treating patients with S aureus infections with high MIC values and to consider the primary source and severity of infection. A confounding factor to direct comparison of the literature is the variations based on the method of MIC determination and testing (Etest vs BMD).

Additionally, all 3 studies addressed the importance of considering clinical patient factors that may lead to poorer prognosis as well as the difficultly in achieving necessary vancomycin levels with limited toxicity. The risk of increased mortality in patients with high vancomycin MICs cannot be ruled out at this time. Therefore, additional patient factors as well as the potential toxicities that may result from vancomycin therapy should be considered when using vancomycin in treating patients with S aureus infections.

Additional Note
An earlier version of this article appeared in the Pharmacy Related Newsletter: The Capsule, of the William S. Middleton Memorial Veterans Hospital.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

Staphylococcus aureus (S aureus) is a common cause of infection within the hospital and in the community.¹ Treatment is based on the organism’s susceptibility to methicillin and is referred to as either MRSA (methicillin-resistant S aureus) or MSSA (methicillin-susceptible 
S aureus). As antibiotic resistance has evolved, patients with S aureus (especially MRSA) infections have become more difficult to treat. Susceptibility testing guides treatment of these infections and determines the minimum inhibitory concentration (MIC) for each antibiotic. A MIC is the minimum concentration of an antibiotic that will inhibit the visible growth of the organism after incubation.

Related: Experts Debate Infection Control Merits of ‘Bare Beneath the Elbows’

Vancomycin has remained the mainstay for treatment of patients with MRSA infections. An increasing number of infections with high documented MICs to vancomycin are raising concern that resistance may be developing. Clinical controversy exists within the infectious disease community as to whether vancomycin is less effective against S aureus infections with a vancomycin MIC of ≥ 2 µg/mL, contributing to poor patient outcomes.²

The Clinical and Laboratory Standards Institute (CLSI) lowered the breakpoint for vancomycin in 2006 from > 4 µg/mL to > 2 µg/mL.³ Breakpoints delineate MIC values that are considered susceptible, nonsusceptible, or resistant to an antibiotic. The CLSI breakpoint change points to an increase in vancomycin resistance and supports the need for further discussion and insight.

A 2012 meta-analysis was conducted to determine whether an association exists between S aureus infections with vancomycin MIC values ≥ 2 µg/mL and the effectiveness of the therapy.² Twenty-two studies were included with a primary outcome of 30-day mortality. A review of MRSA data revealed a statistically significant association between high vancomycin MICs (≥ 1.5 µg/mL) and increased mortality (P < .01), regardless of the source of infection. When limiting the data to Etest (bioMérieux, Marcy L’Etoile, France) MIC testing for MRSA bloodstream infections (BSIs), a vancomycin MIC ≥ 1.5 µg/mL was not associated with increased mortality (P = .08). Comparing data for MIC ≥ 2 µg/mL and ≤ 1.5 µg/mL, found that MICs ≥ 2 µg/mL were associated with increased mortality (P < .01). Analysis of the 11 studies that included data on treatment failure concluded that S aureus infections with a vancomycin MIC ≥ 1.5 µg/mL were associated with an increased risk of treatment failure in both MSSA and MRSA infections (P < .01) and that treatment failure was more likely in MRSA BSIs than in non-BSIs (P < .01).Evidence to support a possible correlation between high S aureus vancomycin MICs and poor patient outcomes came from a 2013 meta-analysis.³ The specific aim of this study was to examine the correlations between vancomycin MIC, patient mortality, and treatment failure. A MIC ≥ 1.5 µg/mL and ≥ 1.0 µg/mL were used to classify MICs as high when determined by Etest and broth microdilution (BMD), respectively. Analysis revealed an association between high vancomycin MICs and increased risk of treatment failure (relative risk [RR] 1.40, 95% confidence interval [CI] 1.15-1.71) and overall mortality (RR 1.42, 95% CI 1.08-1.87). Similarly, a sensitivity analysis on S aureus BSIs with high vancomycin MICs revealed an increased risk of mortality (RR 1.46, 95% CI 1.06-2.01) and treatment failure (RR 1.37, 95% CI 1.09-1.73).

Related: The Importance of an Antimicrobial Stewardship Program

The most recent meta-analysis (published in 2014) included patients with S aureus bacteremia and evaluated the association of high S aureus vancomycin MIC with an increased risk of mortality.⁴ A high MIC was defined as ≥ 1.5 µg/mL by Etest and ≥ 2.0 µg/mL by BMD. The analysis of 38 studies found a nonstatistically significant difference in mortality risk (P = .43). Further analysis was performed to determine whether the vancomycin MIC cutoff plays a role in increased mortality. No statistically significant difference in mortality was found when using a vancomycin MIC ≥ 1.5 µg/mL, ≥ 2.0 µg/mL, ≥ 4.0 µg/mL, or ≥ 8.0 µg/mL. The authors argued that their differing conclusions from other meta-analyses may be due to the inclusion of only bacteremias rather than all infection types, and although there was not a statistically significant difference, increased risk of mortality could not be excluded.

Related: Results Mixed in Hospital Efforts to Tackle Antimicrobial Resistance

Although conclusions of published meta-analyses differ, the results highlight the necessity of using clinical judgment in treating patients with S aureus infections with high MIC values and to consider the primary source and severity of infection. A confounding factor to direct comparison of the literature is the variations based on the method of MIC determination and testing (Etest vs BMD).

Additionally, all 3 studies addressed the importance of considering clinical patient factors that may lead to poorer prognosis as well as the difficultly in achieving necessary vancomycin levels with limited toxicity. The risk of increased mortality in patients with high vancomycin MICs cannot be ruled out at this time. Therefore, additional patient factors as well as the potential toxicities that may result from vancomycin therapy should be considered when using vancomycin in treating patients with S aureus infections.

Additional Note
An earlier version of this article appeared in the Pharmacy Related Newsletter: The Capsule, of the William S. Middleton Memorial Veterans Hospital.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

According to a University of Pennsylvania study, 75% of 123 participants reported having insomnia: 36 reported mild insomnia, and 56 reported moderate-to-severe insomnia. On average, participants said they drank 15.7 drinks per day over the previous 90 days. The only difference between the insomnia groups was on the number of heavy-drinking days; those with moderate-severe insomnia had a significantly higher number. Insomniacs also reported a higher need for addiction treatment, compared with the no-insomnia subjects.

Individuals with moderate-to-severe insomnia had significantly higher scores on the total Short Index of Problems scale, as well as higher subscale scores for physical problems, social problems, and impulse control problems. They had the highest scores for serious conflict with others over the previous month and lifetime conflicts with spouses and mothers. Employment problems increased significantly with severity of insomnia symptoms.

Interestingly, those with only mild insomnia had the most lifetime driving violations. The researchers suggest that when insomnia is at its worst, it intensifies daytime sleepiness, which may keep the sufferer off the road.

Insomnia has been independently associated with psychosocial problems, the researchers note. It’s possible, they say, that people plagued with insomnia and its related symptoms of irritability and anxiety are self-medicating with alcohol. They add that suicidal ideation is common among this group of patients and may be exacerbated by insomnia.

Source
Chaudhary NS, Kampman KM, Kranzler HR, Grandner MA, Debbarma S, Chakravorty S. Addict Behav. 2015;50:165-172.
doi: 10.1016/j.addbeh.2015.06.021.

According to a University of Pennsylvania study, 75% of 123 participants reported having insomnia: 36 reported mild insomnia, and 56 reported moderate-to-severe insomnia. On average, participants said they drank 15.7 drinks per day over the previous 90 days. The only difference between the insomnia groups was on the number of heavy-drinking days; those with moderate-severe insomnia had a significantly higher number. Insomniacs also reported a higher need for addiction treatment, compared with the no-insomnia subjects.

Individuals with moderate-to-severe insomnia had significantly higher scores on the total Short Index of Problems scale, as well as higher subscale scores for physical problems, social problems, and impulse control problems. They had the highest scores for serious conflict with others over the previous month and lifetime conflicts with spouses and mothers. Employment problems increased significantly with severity of insomnia symptoms.

Interestingly, those with only mild insomnia had the most lifetime driving violations. The researchers suggest that when insomnia is at its worst, it intensifies daytime sleepiness, which may keep the sufferer off the road.

Insomnia has been independently associated with psychosocial problems, the researchers note. It’s possible, they say, that people plagued with insomnia and its related symptoms of irritability and anxiety are self-medicating with alcohol. They add that suicidal ideation is common among this group of patients and may be exacerbated by insomnia.

Source
Chaudhary NS, Kampman KM, Kranzler HR, Grandner MA, Debbarma S, Chakravorty S. Addict Behav. 2015;50:165-172.
doi: 10.1016/j.addbeh.2015.06.021.

According to a University of Pennsylvania study, 75% of 123 participants reported having insomnia: 36 reported mild insomnia, and 56 reported moderate-to-severe insomnia. On average, participants said they drank 15.7 drinks per day over the previous 90 days. The only difference between the insomnia groups was on the number of heavy-drinking days; those with moderate-severe insomnia had a significantly higher number. Insomniacs also reported a higher need for addiction treatment, compared with the no-insomnia subjects.

Individuals with moderate-to-severe insomnia had significantly higher scores on the total Short Index of Problems scale, as well as higher subscale scores for physical problems, social problems, and impulse control problems. They had the highest scores for serious conflict with others over the previous month and lifetime conflicts with spouses and mothers. Employment problems increased significantly with severity of insomnia symptoms.

Interestingly, those with only mild insomnia had the most lifetime driving violations. The researchers suggest that when insomnia is at its worst, it intensifies daytime sleepiness, which may keep the sufferer off the road.

Insomnia has been independently associated with psychosocial problems, the researchers note. It’s possible, they say, that people plagued with insomnia and its related symptoms of irritability and anxiety are self-medicating with alcohol. They add that suicidal ideation is common among this group of patients and may be exacerbated by insomnia.

Source
Chaudhary NS, Kampman KM, Kranzler HR, Grandner MA, Debbarma S, Chakravorty S. Addict Behav. 2015;50:165-172.
doi: 10.1016/j.addbeh.2015.06.021.

Many patients inappropriately receive drugs for stress ulcer prophylaxis, and the problem is compounded when the drugs are continued on discharge, say researchers from Banner-University Medical Center in Phoenix and Midwestern University Glendale campus, both in Arizona, and University of Pittsburgh School of Pharmacy in Pennsylvania. They add that although acid suppression therapy plays an important role in reducing the risk of stress-related mucosal disease bleeding in patients in the intensive care unit (ICU), the drugs should be used more judiciously in all patients, particularly given the potential adverse clinical outcomes, such as pneumonia.

Related: Antidepressants Plus NSAIDs and the Risk of Intracranial Hemorrhage

At their hospital, clinical pharmacists have the prescriptive authority to modify stress ulcer prophylaxis to promote use of histamine 2 receptor antagonists (H₂RAs) in ICU patients with risk factors while discontinuing prophylaxis in patients without any indications. Famotidine is the preferred agent at that hospital; pharmacists are authorized to substitute H₂RAs for proton pump inhibitors in ICU patients with major risk factors.

Related: Colonic Dyspnea and the Morgagni Hernia: A Rare Adult Diagnosis

The researchers designed a pharmacist-led program to reduce inappropriate use and reduce costs. They then analyzed data on 1,134 patients, pre- and postimplementation.

The pharmacist program had a “significant impact” on the rate of prophylaxis use, with no difference in clinical outcomes. The appropriate use of famotidine significantly increased in the postimplementation period, from 18% to 89%. The researchers found the preimplementation period had a 41% rate of inappropriate prophylaxis days, compared with 7% after the program. The program also cut down on inappropriate prophylaxis among general ward patients and patients being discharged.

Related: Dabigatran as an Alternative to Warfarin

The program also saved an estimated $200,000 per year in costs associated with medications.

Source
Buckley MS, Park AS, Anderson CS, et al. Am J Med. 2015;128(8):905-913.
doi: 10.1016/j.amjmed.2015.02.014.

Many patients inappropriately receive drugs for stress ulcer prophylaxis, and the problem is compounded when the drugs are continued on discharge, say researchers from Banner-University Medical Center in Phoenix and Midwestern University Glendale campus, both in Arizona, and University of Pittsburgh School of Pharmacy in Pennsylvania. They add that although acid suppression therapy plays an important role in reducing the risk of stress-related mucosal disease bleeding in patients in the intensive care unit (ICU), the drugs should be used more judiciously in all patients, particularly given the potential adverse clinical outcomes, such as pneumonia.

Related: Antidepressants Plus NSAIDs and the Risk of Intracranial Hemorrhage

At their hospital, clinical pharmacists have the prescriptive authority to modify stress ulcer prophylaxis to promote use of histamine 2 receptor antagonists (H₂RAs) in ICU patients with risk factors while discontinuing prophylaxis in patients without any indications. Famotidine is the preferred agent at that hospital; pharmacists are authorized to substitute H₂RAs for proton pump inhibitors in ICU patients with major risk factors.

Related: Colonic Dyspnea and the Morgagni Hernia: A Rare Adult Diagnosis

The researchers designed a pharmacist-led program to reduce inappropriate use and reduce costs. They then analyzed data on 1,134 patients, pre- and postimplementation.

The pharmacist program had a “significant impact” on the rate of prophylaxis use, with no difference in clinical outcomes. The appropriate use of famotidine significantly increased in the postimplementation period, from 18% to 89%. The researchers found the preimplementation period had a 41% rate of inappropriate prophylaxis days, compared with 7% after the program. The program also cut down on inappropriate prophylaxis among general ward patients and patients being discharged.

Related: Dabigatran as an Alternative to Warfarin

The program also saved an estimated $200,000 per year in costs associated with medications.

Source
Buckley MS, Park AS, Anderson CS, et al. Am J Med. 2015;128(8):905-913.
doi: 10.1016/j.amjmed.2015.02.014.

Many patients inappropriately receive drugs for stress ulcer prophylaxis, and the problem is compounded when the drugs are continued on discharge, say researchers from Banner-University Medical Center in Phoenix and Midwestern University Glendale campus, both in Arizona, and University of Pittsburgh School of Pharmacy in Pennsylvania. They add that although acid suppression therapy plays an important role in reducing the risk of stress-related mucosal disease bleeding in patients in the intensive care unit (ICU), the drugs should be used more judiciously in all patients, particularly given the potential adverse clinical outcomes, such as pneumonia.

Related: Antidepressants Plus NSAIDs and the Risk of Intracranial Hemorrhage

At their hospital, clinical pharmacists have the prescriptive authority to modify stress ulcer prophylaxis to promote use of histamine 2 receptor antagonists (H₂RAs) in ICU patients with risk factors while discontinuing prophylaxis in patients without any indications. Famotidine is the preferred agent at that hospital; pharmacists are authorized to substitute H₂RAs for proton pump inhibitors in ICU patients with major risk factors.

Related: Colonic Dyspnea and the Morgagni Hernia: A Rare Adult Diagnosis

The researchers designed a pharmacist-led program to reduce inappropriate use and reduce costs. They then analyzed data on 1,134 patients, pre- and postimplementation.

The pharmacist program had a “significant impact” on the rate of prophylaxis use, with no difference in clinical outcomes. The appropriate use of famotidine significantly increased in the postimplementation period, from 18% to 89%. The researchers found the preimplementation period had a 41% rate of inappropriate prophylaxis days, compared with 7% after the program. The program also cut down on inappropriate prophylaxis among general ward patients and patients being discharged.

Related: Dabigatran as an Alternative to Warfarin

The program also saved an estimated $200,000 per year in costs associated with medications.

Source
Buckley MS, Park AS, Anderson CS, et al. Am J Med. 2015;128(8):905-913.
doi: 10.1016/j.amjmed.2015.02.014.

Antidepressants—especially selective serotonin reuptake inhibitors (SSRIs)—and nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with increasing the risk of abnormal bleeding, usually gastrointestinal bleeding. Neither of the drug groups have been linked to a higher risk of intracranial hemorrhage (ICH), but little is known about that risk, say researchers from Seoul National University in South Korea. However, their analysis of data from nearly 5 million people, using both antidepressants and NSAIDs, increased the 30-day risk of ICH (hazard ratio, 1.6).

Related:Management of Comorbid Sleep Disorders in Patients With Posttraumatic Stress Disorder

The study included patients who began receiving antidepressants without having received a prescription for antidepressants during the preceding year. Antidepressants included serotonin-norepinephrine reuptake inhibitors, SSRIs, and tricyclic antidepressants.

Among people who used only antidepressants, the incidence rate of events was 1.6 per 1,000 person-years. Among those who used both antidepressants and NSAIDs, the rate was 5.7.

Related:A Multidisciplinary Chronic Pain Management Clinic in an Indian Health Service Facility

Men had the highest risk for intracranial hemorrhage. The combined use seemed to not have a major effect on patients who already had risk factors for ICH, such as advancing age and receiving antithrombotic agents, the researchers say. They also found no statistically meaningful differences in risk of ICH among the antidepressant drug classes.

To the best of their knowledge, the researchers say, this is the first population-based cohort study focusing on the risk of ICH with combined use of antidepressants and NSAIDs. Other studies have mostly been case-control, they say, examining abnormal bleeding risk from SSRIs.

Related:Testosterone Replacement Therapy: Playing Catch-up With Patients

Source: Shin J-U, Park M-J, Lee SH, et al. BMJ. 2015;351:h3517.
doi: 10.1136/bmj.h3517. 

Antidepressants—especially selective serotonin reuptake inhibitors (SSRIs)—and nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with increasing the risk of abnormal bleeding, usually gastrointestinal bleeding. Neither of the drug groups have been linked to a higher risk of intracranial hemorrhage (ICH), but little is known about that risk, say researchers from Seoul National University in South Korea. However, their analysis of data from nearly 5 million people, using both antidepressants and NSAIDs, increased the 30-day risk of ICH (hazard ratio, 1.6).

Related:Management of Comorbid Sleep Disorders in Patients With Posttraumatic Stress Disorder

The study included patients who began receiving antidepressants without having received a prescription for antidepressants during the preceding year. Antidepressants included serotonin-norepinephrine reuptake inhibitors, SSRIs, and tricyclic antidepressants.

Among people who used only antidepressants, the incidence rate of events was 1.6 per 1,000 person-years. Among those who used both antidepressants and NSAIDs, the rate was 5.7.

Related:A Multidisciplinary Chronic Pain Management Clinic in an Indian Health Service Facility

Men had the highest risk for intracranial hemorrhage. The combined use seemed to not have a major effect on patients who already had risk factors for ICH, such as advancing age and receiving antithrombotic agents, the researchers say. They also found no statistically meaningful differences in risk of ICH among the antidepressant drug classes.

To the best of their knowledge, the researchers say, this is the first population-based cohort study focusing on the risk of ICH with combined use of antidepressants and NSAIDs. Other studies have mostly been case-control, they say, examining abnormal bleeding risk from SSRIs.

Related:Testosterone Replacement Therapy: Playing Catch-up With Patients

Source: Shin J-U, Park M-J, Lee SH, et al. BMJ. 2015;351:h3517.
doi: 10.1136/bmj.h3517. 

Antidepressants—especially selective serotonin reuptake inhibitors (SSRIs)—and nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with increasing the risk of abnormal bleeding, usually gastrointestinal bleeding. Neither of the drug groups have been linked to a higher risk of intracranial hemorrhage (ICH), but little is known about that risk, say researchers from Seoul National University in South Korea. However, their analysis of data from nearly 5 million people, using both antidepressants and NSAIDs, increased the 30-day risk of ICH (hazard ratio, 1.6).

Related:Management of Comorbid Sleep Disorders in Patients With Posttraumatic Stress Disorder

The study included patients who began receiving antidepressants without having received a prescription for antidepressants during the preceding year. Antidepressants included serotonin-norepinephrine reuptake inhibitors, SSRIs, and tricyclic antidepressants.

Among people who used only antidepressants, the incidence rate of events was 1.6 per 1,000 person-years. Among those who used both antidepressants and NSAIDs, the rate was 5.7.

Related:A Multidisciplinary Chronic Pain Management Clinic in an Indian Health Service Facility

Men had the highest risk for intracranial hemorrhage. The combined use seemed to not have a major effect on patients who already had risk factors for ICH, such as advancing age and receiving antithrombotic agents, the researchers say. They also found no statistically meaningful differences in risk of ICH among the antidepressant drug classes.

To the best of their knowledge, the researchers say, this is the first population-based cohort study focusing on the risk of ICH with combined use of antidepressants and NSAIDs. Other studies have mostly been case-control, they say, examining abnormal bleeding risk from SSRIs.

Related:Testosterone Replacement Therapy: Playing Catch-up With Patients

Source: Shin J-U, Park M-J, Lee SH, et al. BMJ. 2015;351:h3517.
doi: 10.1136/bmj.h3517. 

Knowing what a woman values most highly in a contraceptive can help guide the health care conversation, say researchers from Washington University in St. Louis, who studied nearly 3,000 women enrolled in the Contraceptive CHOICE Project. Safety and effectiveness topped the general wish list; other factors weighed more or less heavily, according to the individual woman.

Related: Navy Triples Paid Maternity Leave

Of the 2,590 women who completed the survey, 99.6% had used contraceptives, usually oral contraceptives and condoms. When choosing a method, they considered cost, whether the contraceptive is long lasting, whether it’s hard to remember to take or use it, and whether it protects against sexually transmitted infections. Health care providers’ recommendations also scored high. The women did not rate the influence of partner, family, friends, or religious community highly.

More than 40% ranked adverse effects (AEs) among the 3 most important factors. The majority had experienced ≥ 1 AE with a contraceptive method in the past, and 60% of those women had discontinued a method because of the AE.

Related: HHS Grants Expand Home Visiting

Tailored counseling is “essential” when talking to women about contraceptives, the researchers say, because many attributes are important. Moreover, they cite studies that have found personalized contraceptive counseling can improve adherence and satisfaction. However, it’s also important to educate women more fully, they advise. For instance, they found that women who said avoiding irregular bleeding or having a regular period were important factors were less likely to choose the copper intrauterine device (IUD), even though that device could resolve their concerns.

One potential limitation to their study, the researchers say, is that the respondents were all participants in the CHOICE Project (a prospective cohort study designed to promote the use of long-acting reversible contraception) and might not be representative of other populations of women. Use of IUDs and implants was much higher among the CHOICE participants than that of the nation: 75%, compared with 8.5%.

Related: Overprescription of Opioids in Women of Childbearing Age

Nonetheless, their findings have promise for health care visits, the researchers say. Once providers understand which attributes are most important to the women they care for, they can present contraceptive methods in an appropriate order, making counseling more effective and efficient.

Knowing what a woman values most highly in a contraceptive can help guide the health care conversation, say researchers from Washington University in St. Louis, who studied nearly 3,000 women enrolled in the Contraceptive CHOICE Project. Safety and effectiveness topped the general wish list; other factors weighed more or less heavily, according to the individual woman.

Related: Navy Triples Paid Maternity Leave

Of the 2,590 women who completed the survey, 99.6% had used contraceptives, usually oral contraceptives and condoms. When choosing a method, they considered cost, whether the contraceptive is long lasting, whether it’s hard to remember to take or use it, and whether it protects against sexually transmitted infections. Health care providers’ recommendations also scored high. The women did not rate the influence of partner, family, friends, or religious community highly.

More than 40% ranked adverse effects (AEs) among the 3 most important factors. The majority had experienced ≥ 1 AE with a contraceptive method in the past, and 60% of those women had discontinued a method because of the AE.

Related: HHS Grants Expand Home Visiting

Tailored counseling is “essential” when talking to women about contraceptives, the researchers say, because many attributes are important. Moreover, they cite studies that have found personalized contraceptive counseling can improve adherence and satisfaction. However, it’s also important to educate women more fully, they advise. For instance, they found that women who said avoiding irregular bleeding or having a regular period were important factors were less likely to choose the copper intrauterine device (IUD), even though that device could resolve their concerns.

One potential limitation to their study, the researchers say, is that the respondents were all participants in the CHOICE Project (a prospective cohort study designed to promote the use of long-acting reversible contraception) and might not be representative of other populations of women. Use of IUDs and implants was much higher among the CHOICE participants than that of the nation: 75%, compared with 8.5%.

Related: Overprescription of Opioids in Women of Childbearing Age

Nonetheless, their findings have promise for health care visits, the researchers say. Once providers understand which attributes are most important to the women they care for, they can present contraceptive methods in an appropriate order, making counseling more effective and efficient.

Knowing what a woman values most highly in a contraceptive can help guide the health care conversation, say researchers from Washington University in St. Louis, who studied nearly 3,000 women enrolled in the Contraceptive CHOICE Project. Safety and effectiveness topped the general wish list; other factors weighed more or less heavily, according to the individual woman.

Related: Navy Triples Paid Maternity Leave

Of the 2,590 women who completed the survey, 99.6% had used contraceptives, usually oral contraceptives and condoms. When choosing a method, they considered cost, whether the contraceptive is long lasting, whether it’s hard to remember to take or use it, and whether it protects against sexually transmitted infections. Health care providers’ recommendations also scored high. The women did not rate the influence of partner, family, friends, or religious community highly.

More than 40% ranked adverse effects (AEs) among the 3 most important factors. The majority had experienced ≥ 1 AE with a contraceptive method in the past, and 60% of those women had discontinued a method because of the AE.

Related: HHS Grants Expand Home Visiting

Tailored counseling is “essential” when talking to women about contraceptives, the researchers say, because many attributes are important. Moreover, they cite studies that have found personalized contraceptive counseling can improve adherence and satisfaction. However, it’s also important to educate women more fully, they advise. For instance, they found that women who said avoiding irregular bleeding or having a regular period were important factors were less likely to choose the copper intrauterine device (IUD), even though that device could resolve their concerns.

One potential limitation to their study, the researchers say, is that the respondents were all participants in the CHOICE Project (a prospective cohort study designed to promote the use of long-acting reversible contraception) and might not be representative of other populations of women. Use of IUDs and implants was much higher among the CHOICE participants than that of the nation: 75%, compared with 8.5%.

Related: Overprescription of Opioids in Women of Childbearing Age

Nonetheless, their findings have promise for health care visits, the researchers say. Once providers understand which attributes are most important to the women they care for, they can present contraceptive methods in an appropriate order, making counseling more effective and efficient.

A simple, fast screening questionnaire for substance use could have several benefits, say researchers from New York University and Boston Medical Center, such as streamlining workflow for primary care practitioners and staff and affording patients the privacy to report possibly stigmatizing behavior.

Related: Veterans' Use of Designer Cathinones and Cannabinoids

But there wasn’t such a tool, so the researchers developed the Substance Use Brief Screen (SUBS). They based it on the National Institute on Drug Abuse Quick Screen V1.0, which has not yet been validated. Then they tested their screen for reliability in 54 primary care patients and conducted another study to validate it in 586 more.

The questionnaire has 4 questions: In the past 12 months, how many days did you use tobacco; have 4 or more alcoholic drinks in a day; use illegal drug(s); or use prescription medication(s) “recreationally”?

Related: Tracking Tramadol-Related ED Visits

The SUBS had high sensitivity and moderate-to-high specificity for detecting unhealthy use of tobacco, alcohol, and other drugs. Sensitivity was lower for prescription drugs alone but increased when they were combined into a single “any drug” category. The researchers say this may reflect drug users’ lack of clarity about what constitutes illicit vs prescription drug misuse.

Related: Living Tobacco Free

The test was well accepted among a diverse patient population (although 11% in the reliability study needed some help with questions or technical assistance) and easily used on a tablet computer. It compared favorably with other widely recommended brief substance use screening tools—all of which are interviewer administered, the researchers point out. They add that a self-administered tool may put patients at greater ease about reporting substance use and thus be more consistently accurate in real-world practice.

Source
McNeely J, Strauss SM, Saitz R, et al. Am J Med. 2015;128(7):784.e9-784.e19.
doi: 10.1016/j.amjmed.2015.02.007.

A simple, fast screening questionnaire for substance use could have several benefits, say researchers from New York University and Boston Medical Center, such as streamlining workflow for primary care practitioners and staff and affording patients the privacy to report possibly stigmatizing behavior.

Related: Veterans' Use of Designer Cathinones and Cannabinoids

But there wasn’t such a tool, so the researchers developed the Substance Use Brief Screen (SUBS). They based it on the National Institute on Drug Abuse Quick Screen V1.0, which has not yet been validated. Then they tested their screen for reliability in 54 primary care patients and conducted another study to validate it in 586 more.

The questionnaire has 4 questions: In the past 12 months, how many days did you use tobacco; have 4 or more alcoholic drinks in a day; use illegal drug(s); or use prescription medication(s) “recreationally”?

Related: Tracking Tramadol-Related ED Visits

The SUBS had high sensitivity and moderate-to-high specificity for detecting unhealthy use of tobacco, alcohol, and other drugs. Sensitivity was lower for prescription drugs alone but increased when they were combined into a single “any drug” category. The researchers say this may reflect drug users’ lack of clarity about what constitutes illicit vs prescription drug misuse.

Related: Living Tobacco Free

The test was well accepted among a diverse patient population (although 11% in the reliability study needed some help with questions or technical assistance) and easily used on a tablet computer. It compared favorably with other widely recommended brief substance use screening tools—all of which are interviewer administered, the researchers point out. They add that a self-administered tool may put patients at greater ease about reporting substance use and thus be more consistently accurate in real-world practice.

Source
McNeely J, Strauss SM, Saitz R, et al. Am J Med. 2015;128(7):784.e9-784.e19.
doi: 10.1016/j.amjmed.2015.02.007.

A simple, fast screening questionnaire for substance use could have several benefits, say researchers from New York University and Boston Medical Center, such as streamlining workflow for primary care practitioners and staff and affording patients the privacy to report possibly stigmatizing behavior.

Related: Veterans' Use of Designer Cathinones and Cannabinoids

But there wasn’t such a tool, so the researchers developed the Substance Use Brief Screen (SUBS). They based it on the National Institute on Drug Abuse Quick Screen V1.0, which has not yet been validated. Then they tested their screen for reliability in 54 primary care patients and conducted another study to validate it in 586 more.

The questionnaire has 4 questions: In the past 12 months, how many days did you use tobacco; have 4 or more alcoholic drinks in a day; use illegal drug(s); or use prescription medication(s) “recreationally”?

Related: Tracking Tramadol-Related ED Visits

The SUBS had high sensitivity and moderate-to-high specificity for detecting unhealthy use of tobacco, alcohol, and other drugs. Sensitivity was lower for prescription drugs alone but increased when they were combined into a single “any drug” category. The researchers say this may reflect drug users’ lack of clarity about what constitutes illicit vs prescription drug misuse.

Related: Living Tobacco Free

The test was well accepted among a diverse patient population (although 11% in the reliability study needed some help with questions or technical assistance) and easily used on a tablet computer. It compared favorably with other widely recommended brief substance use screening tools—all of which are interviewer administered, the researchers point out. They add that a self-administered tool may put patients at greater ease about reporting substance use and thus be more consistently accurate in real-world practice.

Source
McNeely J, Strauss SM, Saitz R, et al. Am J Med. 2015;128(7):784.e9-784.e19.
doi: 10.1016/j.amjmed.2015.02.007.

The combination of prolonged-release oxycodone and naloxone (PR OXN) better relieves pain and opioid-induced constipation than does prolonged-release oxycodone (PR OXY) alone, according to a team of Belgian researchers.

In their study, 65 patients with laxative-refractory opioid-induced constipation (OIC) were given PR OXY or PR OXN at a median dose of 20 mg/d. They were assessed for pain and constipation relief during 3 visits conducted over 12 weeks.

Related: Reducing Opioid Use for Chronic Pain

Study results showed PR OXN was superior to PR OXY in pain relief, OIC, and quality of life. The Bowel Function Index (BFI) showed a statistically significant and clinically relevant improvement of 48.5 points from visit 1 to visit 3 (P < .001; 95% confidence interval [CI], 44.4-52.7).

The researchers note that a change in the BFI of ≥ 12 points is related to clinically meaningful changes in bowel habits in patients with OIC. The average BFI was < 28.8 after 6 weeks of PR OXN, indicating that most patients were no longer constipated despite opioid treatment.

Related: Overprescription of Opioids in Women of Childbearing Age

The mean pain score was significantly reduced, on average 2.1 units during treatment (P < .001; 95% CI, 1.66-2.54). At 18 weeks, the mean score was 3.8, on a scale of 0 to 10.

The researchers say the median PR OXN dose remained consistent throughout the study. Moreover, the number of patients who used analgesic rescue medication in the 7 days before each visit was reduced from 44 (64.7%) to 26 (41.9%). Therefore, the researchers say, the improved pain relief cannot be explained by an increased dose or increased use of rescue medication and is probably related to the improved constipation relief.

Related: E-Consults in Gastroenterology: A Quality Improvement Project

Quality of life scores increased significantly. Only 2 patients reported an adverse event, both of which were mild or unrelated to the study treatment.

When the study began, the patients were each using at least 2 laxatives with different mechanisms of action. During the study, the number of patients using laxatives in the 7 days before each visit dropped significantly, from 65 to 24 by visit 3. The researchers say, to the best of their knowledge, this is the only noninterventional study of opioid treatment in which laxative use was documented before and during treatment.

The improvement in OIC the researchers observed during PR OXN treatment was not due to laxatives, thus their findings support the rationale that PR OXN treatment counteracts OIC through mechanisms other than those of laxatives and addresses the underlying mechanism of OIC.

Source
Poelaert J, Koopmans-Klein G, Dioh A, et al. Clin Ther. 2015;37(4):784-792.
doi: 10.1016/j.clinthera.2015.02.010.

The combination of prolonged-release oxycodone and naloxone (PR OXN) better relieves pain and opioid-induced constipation than does prolonged-release oxycodone (PR OXY) alone, according to a team of Belgian researchers.

In their study, 65 patients with laxative-refractory opioid-induced constipation (OIC) were given PR OXY or PR OXN at a median dose of 20 mg/d. They were assessed for pain and constipation relief during 3 visits conducted over 12 weeks.

Related: Reducing Opioid Use for Chronic Pain

Study results showed PR OXN was superior to PR OXY in pain relief, OIC, and quality of life. The Bowel Function Index (BFI) showed a statistically significant and clinically relevant improvement of 48.5 points from visit 1 to visit 3 (P < .001; 95% confidence interval [CI], 44.4-52.7).

The researchers note that a change in the BFI of ≥ 12 points is related to clinically meaningful changes in bowel habits in patients with OIC. The average BFI was < 28.8 after 6 weeks of PR OXN, indicating that most patients were no longer constipated despite opioid treatment.

Related: Overprescription of Opioids in Women of Childbearing Age

The mean pain score was significantly reduced, on average 2.1 units during treatment (P < .001; 95% CI, 1.66-2.54). At 18 weeks, the mean score was 3.8, on a scale of 0 to 10.

The researchers say the median PR OXN dose remained consistent throughout the study. Moreover, the number of patients who used analgesic rescue medication in the 7 days before each visit was reduced from 44 (64.7%) to 26 (41.9%). Therefore, the researchers say, the improved pain relief cannot be explained by an increased dose or increased use of rescue medication and is probably related to the improved constipation relief.

Related: E-Consults in Gastroenterology: A Quality Improvement Project

Quality of life scores increased significantly. Only 2 patients reported an adverse event, both of which were mild or unrelated to the study treatment.

When the study began, the patients were each using at least 2 laxatives with different mechanisms of action. During the study, the number of patients using laxatives in the 7 days before each visit dropped significantly, from 65 to 24 by visit 3. The researchers say, to the best of their knowledge, this is the only noninterventional study of opioid treatment in which laxative use was documented before and during treatment.

The improvement in OIC the researchers observed during PR OXN treatment was not due to laxatives, thus their findings support the rationale that PR OXN treatment counteracts OIC through mechanisms other than those of laxatives and addresses the underlying mechanism of OIC.

Source
Poelaert J, Koopmans-Klein G, Dioh A, et al. Clin Ther. 2015;37(4):784-792.
doi: 10.1016/j.clinthera.2015.02.010.

The combination of prolonged-release oxycodone and naloxone (PR OXN) better relieves pain and opioid-induced constipation than does prolonged-release oxycodone (PR OXY) alone, according to a team of Belgian researchers.

In their study, 65 patients with laxative-refractory opioid-induced constipation (OIC) were given PR OXY or PR OXN at a median dose of 20 mg/d. They were assessed for pain and constipation relief during 3 visits conducted over 12 weeks.

Related: Reducing Opioid Use for Chronic Pain

Study results showed PR OXN was superior to PR OXY in pain relief, OIC, and quality of life. The Bowel Function Index (BFI) showed a statistically significant and clinically relevant improvement of 48.5 points from visit 1 to visit 3 (P < .001; 95% confidence interval [CI], 44.4-52.7).

The researchers note that a change in the BFI of ≥ 12 points is related to clinically meaningful changes in bowel habits in patients with OIC. The average BFI was < 28.8 after 6 weeks of PR OXN, indicating that most patients were no longer constipated despite opioid treatment.

Related: Overprescription of Opioids in Women of Childbearing Age

The mean pain score was significantly reduced, on average 2.1 units during treatment (P < .001; 95% CI, 1.66-2.54). At 18 weeks, the mean score was 3.8, on a scale of 0 to 10.

The researchers say the median PR OXN dose remained consistent throughout the study. Moreover, the number of patients who used analgesic rescue medication in the 7 days before each visit was reduced from 44 (64.7%) to 26 (41.9%). Therefore, the researchers say, the improved pain relief cannot be explained by an increased dose or increased use of rescue medication and is probably related to the improved constipation relief.

Related: E-Consults in Gastroenterology: A Quality Improvement Project

Quality of life scores increased significantly. Only 2 patients reported an adverse event, both of which were mild or unrelated to the study treatment.

When the study began, the patients were each using at least 2 laxatives with different mechanisms of action. During the study, the number of patients using laxatives in the 7 days before each visit dropped significantly, from 65 to 24 by visit 3. The researchers say, to the best of their knowledge, this is the only noninterventional study of opioid treatment in which laxative use was documented before and during treatment.

The improvement in OIC the researchers observed during PR OXN treatment was not due to laxatives, thus their findings support the rationale that PR OXN treatment counteracts OIC through mechanisms other than those of laxatives and addresses the underlying mechanism of OIC.

Source
Poelaert J, Koopmans-Klein G, Dioh A, et al. Clin Ther. 2015;37(4):784-792.
doi: 10.1016/j.clinthera.2015.02.010.

Pseudomonas is a genus of aerobic, Gram-negative bacilli consisting of about 200 species. Pseudomonas aeruginosa (P aeruginosa) is the species most commonly associated with serious hospital-acquired infections and is commonly found in moist environments in hospitals, such as sinks, showers, and machinery/equipment. The symptoms of an infection by this bacterium are variable based on the site of infection and can manifest in various sites, such as the respiratory tract, urinary tract, ears, eyes, heart, skin, and soft tissue.¹ General risk factors for infection with P aeruginosa include immunosuppression, history of lung disease, hospitalization lasting at least 5 days, history of repeated antibiotic use within 90 days, and a history of pseudomonal colonization/infection.

Related: Antibiotic Therapy and Bacterial Resistance in Patients With Spinal Cord Injury

Pseudomonas aeruginosa is a challenging organism to manage, as it is inherently resistant to many antibiotics. Furthermore, antibiotics effective against infections caused by P aeruginosa often require specific regimens as a result of the high minimum inhibitory concentration (MIC) of the organism. Two specific strategies that have been analyzed for proper coverage of P aeruginosa include the use of higher than usual doses and extended infusions. Due to significant challenges associated with obtaining patient outcomes data in human clinical trials, researchers often use Monte Carlo simulations, which are computational algorithms that simulate the variables of a study (ie, patient demographics) to be as real as possible to accurately predict therapeutic responses in patients.

Analyzing pharmacokinetic (PK) and pharmacodynamic (PD) indexes is valuable for determining therapeutic efficacy, as these indexes consider both the antibiotic dose/concentration and its effect over time in relation to response to therapy. The free-drug area under the concentration time curve (fAUC/MIC) ratio is a PK/PD value commonly used to describe the free-drug concentration over 24 hours that is above the MIC.² The fAUC is dependent on creatinine clearance (CrCl) and, therefore, is specific to each patient. A threshold value for the fAUC/MIC is determined for an antibiotic, and a therapeutic regimen is dosed accordingly to assure fAUC/MIC attainment above the minimum threshold. The probability of target attainment (PTA), which is the probability that the threshold value of a PD index is achieved at a certain MIC, and the probability of cure (POC) for a given antibiotic regimen are used to determine the efficacy of an antibiotic in Monte Carlo simulations.²

Related: Bacteremia From an Unlikely Source

A study by Zelenitsky and colleagues evaluated the efficacy of 3 ciprofloxacin dosing regimens using Monte Carlo simulations (400 mg IV every 12 hours [standard dose], 400 mg IV every 8 hours [high dose], and a PD-targeted regimen dosed to attain an fAUC/MIC value > 86).³ An fAUC/MIC value of 86 was previously determined to predict cure rates of at least 90%.⁴ The Clinical and Laboratory Standards Institute defines a P aeruginosa MIC of ≤ 1 μg/mL to be susceptible and an MIC of ≥ 4 μg/mL to be resistant to ciprofloxacin.⁵

The researchers determined PTA and POC values for each regimen based on various MICs. The in vitro laboratory simulations revealed the PTA and POC values approached 100% for all 3 regimens when the MIC was 0.125 μg/mL. However, when the MIC was 1 μg/mL, the PTA for the standard and high dose was 0%, and the PD-targeted regimen was 40%. The POC was 27%, 40%, and 72% for the standard dose, high dose, and the PD-targeted regimen, respectively. Although the PD-targeted regimen was the most efficacious, it took doses exceeding 1,300 mg and 1,800 mg daily to achieve similar results. In addition, PD-targeted regimens are not practical for dosing due to patient variability in CrCl. From these simulations, it was concluded that the high dose of ciprofloxacin 400 mg IV every 8 hours should be recommended for treating Pseudomonas infections in patients with normal renal function.

Related: Antimicrobial Stewardship in an Outpatient Parenteral Antibiotic Therapy Program

In another study by Lodise and colleagues, researchers examined the clinical implications of an extended-infusion dosing strategy for piperacillin-tazobactam in the critically ill.⁶ The 2 piperacillin- tazobactam regimens evaluated were 3.375 g IV over 30 minutes given every 4 or 6 hours and 3.375 g IV over 4 hours given every 8 hours. The 14-day mortality rate in critically ill patients who received the extended- and intermittent-infusion regimens was 12.2% and 31.6%, respectively (P = .04). Additionally, patients receiving the extended-infusion regimen had a decreased in-house length of stay compared with the intermittent-infusion group (21 vs 38 days, P = .02). Despite having a lower drug concentration peak, the extended-infusion regimen maintains steady drug concentrations above the MIC for a greater period, resulting in prolonged therapeutic efficacy. Other antibiotics (cefepime⁷ and ceftazidime⁸) have been studied by using the same methodology of comparing intermittent and extended infusions and have had similar results.

Given the management challenges associated with P aeruginosa infections, it is important for clinicians to recognize patients who may have or be at risk of infection with P aeruginosa and use appropriate dosing regimens to effectively manage infections and improve patient outcomes.

Additional Note
An earlier version of this article appeared in the Pharmacy Related Newsletter: The Capsule, of the William S. Middleton Memorial Veterans Hospital.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

Pseudomonas is a genus of aerobic, Gram-negative bacilli consisting of about 200 species. Pseudomonas aeruginosa (P aeruginosa) is the species most commonly associated with serious hospital-acquired infections and is commonly found in moist environments in hospitals, such as sinks, showers, and machinery/equipment. The symptoms of an infection by this bacterium are variable based on the site of infection and can manifest in various sites, such as the respiratory tract, urinary tract, ears, eyes, heart, skin, and soft tissue.¹ General risk factors for infection with P aeruginosa include immunosuppression, history of lung disease, hospitalization lasting at least 5 days, history of repeated antibiotic use within 90 days, and a history of pseudomonal colonization/infection.

Related: Antibiotic Therapy and Bacterial Resistance in Patients With Spinal Cord Injury

Pseudomonas aeruginosa is a challenging organism to manage, as it is inherently resistant to many antibiotics. Furthermore, antibiotics effective against infections caused by P aeruginosa often require specific regimens as a result of the high minimum inhibitory concentration (MIC) of the organism. Two specific strategies that have been analyzed for proper coverage of P aeruginosa include the use of higher than usual doses and extended infusions. Due to significant challenges associated with obtaining patient outcomes data in human clinical trials, researchers often use Monte Carlo simulations, which are computational algorithms that simulate the variables of a study (ie, patient demographics) to be as real as possible to accurately predict therapeutic responses in patients.

Analyzing pharmacokinetic (PK) and pharmacodynamic (PD) indexes is valuable for determining therapeutic efficacy, as these indexes consider both the antibiotic dose/concentration and its effect over time in relation to response to therapy. The free-drug area under the concentration time curve (fAUC/MIC) ratio is a PK/PD value commonly used to describe the free-drug concentration over 24 hours that is above the MIC.² The fAUC is dependent on creatinine clearance (CrCl) and, therefore, is specific to each patient. A threshold value for the fAUC/MIC is determined for an antibiotic, and a therapeutic regimen is dosed accordingly to assure fAUC/MIC attainment above the minimum threshold. The probability of target attainment (PTA), which is the probability that the threshold value of a PD index is achieved at a certain MIC, and the probability of cure (POC) for a given antibiotic regimen are used to determine the efficacy of an antibiotic in Monte Carlo simulations.²

Related: Bacteremia From an Unlikely Source

A study by Zelenitsky and colleagues evaluated the efficacy of 3 ciprofloxacin dosing regimens using Monte Carlo simulations (400 mg IV every 12 hours [standard dose], 400 mg IV every 8 hours [high dose], and a PD-targeted regimen dosed to attain an fAUC/MIC value > 86).³ An fAUC/MIC value of 86 was previously determined to predict cure rates of at least 90%.⁴ The Clinical and Laboratory Standards Institute defines a P aeruginosa MIC of ≤ 1 μg/mL to be susceptible and an MIC of ≥ 4 μg/mL to be resistant to ciprofloxacin.⁵

The researchers determined PTA and POC values for each regimen based on various MICs. The in vitro laboratory simulations revealed the PTA and POC values approached 100% for all 3 regimens when the MIC was 0.125 μg/mL. However, when the MIC was 1 μg/mL, the PTA for the standard and high dose was 0%, and the PD-targeted regimen was 40%. The POC was 27%, 40%, and 72% for the standard dose, high dose, and the PD-targeted regimen, respectively. Although the PD-targeted regimen was the most efficacious, it took doses exceeding 1,300 mg and 1,800 mg daily to achieve similar results. In addition, PD-targeted regimens are not practical for dosing due to patient variability in CrCl. From these simulations, it was concluded that the high dose of ciprofloxacin 400 mg IV every 8 hours should be recommended for treating Pseudomonas infections in patients with normal renal function.

Related: Antimicrobial Stewardship in an Outpatient Parenteral Antibiotic Therapy Program

In another study by Lodise and colleagues, researchers examined the clinical implications of an extended-infusion dosing strategy for piperacillin-tazobactam in the critically ill.⁶ The 2 piperacillin- tazobactam regimens evaluated were 3.375 g IV over 30 minutes given every 4 or 6 hours and 3.375 g IV over 4 hours given every 8 hours. The 14-day mortality rate in critically ill patients who received the extended- and intermittent-infusion regimens was 12.2% and 31.6%, respectively (P = .04). Additionally, patients receiving the extended-infusion regimen had a decreased in-house length of stay compared with the intermittent-infusion group (21 vs 38 days, P = .02). Despite having a lower drug concentration peak, the extended-infusion regimen maintains steady drug concentrations above the MIC for a greater period, resulting in prolonged therapeutic efficacy. Other antibiotics (cefepime⁷ and ceftazidime⁸) have been studied by using the same methodology of comparing intermittent and extended infusions and have had similar results.

Given the management challenges associated with P aeruginosa infections, it is important for clinicians to recognize patients who may have or be at risk of infection with P aeruginosa and use appropriate dosing regimens to effectively manage infections and improve patient outcomes.

Additional Note
An earlier version of this article appeared in the Pharmacy Related Newsletter: The Capsule, of the William S. Middleton Memorial Veterans Hospital.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

Pseudomonas is a genus of aerobic, Gram-negative bacilli consisting of about 200 species. Pseudomonas aeruginosa (P aeruginosa) is the species most commonly associated with serious hospital-acquired infections and is commonly found in moist environments in hospitals, such as sinks, showers, and machinery/equipment. The symptoms of an infection by this bacterium are variable based on the site of infection and can manifest in various sites, such as the respiratory tract, urinary tract, ears, eyes, heart, skin, and soft tissue.¹ General risk factors for infection with P aeruginosa include immunosuppression, history of lung disease, hospitalization lasting at least 5 days, history of repeated antibiotic use within 90 days, and a history of pseudomonal colonization/infection.

Related: Antibiotic Therapy and Bacterial Resistance in Patients With Spinal Cord Injury

Pseudomonas aeruginosa is a challenging organism to manage, as it is inherently resistant to many antibiotics. Furthermore, antibiotics effective against infections caused by P aeruginosa often require specific regimens as a result of the high minimum inhibitory concentration (MIC) of the organism. Two specific strategies that have been analyzed for proper coverage of P aeruginosa include the use of higher than usual doses and extended infusions. Due to significant challenges associated with obtaining patient outcomes data in human clinical trials, researchers often use Monte Carlo simulations, which are computational algorithms that simulate the variables of a study (ie, patient demographics) to be as real as possible to accurately predict therapeutic responses in patients.

Analyzing pharmacokinetic (PK) and pharmacodynamic (PD) indexes is valuable for determining therapeutic efficacy, as these indexes consider both the antibiotic dose/concentration and its effect over time in relation to response to therapy. The free-drug area under the concentration time curve (fAUC/MIC) ratio is a PK/PD value commonly used to describe the free-drug concentration over 24 hours that is above the MIC.² The fAUC is dependent on creatinine clearance (CrCl) and, therefore, is specific to each patient. A threshold value for the fAUC/MIC is determined for an antibiotic, and a therapeutic regimen is dosed accordingly to assure fAUC/MIC attainment above the minimum threshold. The probability of target attainment (PTA), which is the probability that the threshold value of a PD index is achieved at a certain MIC, and the probability of cure (POC) for a given antibiotic regimen are used to determine the efficacy of an antibiotic in Monte Carlo simulations.²

Related: Bacteremia From an Unlikely Source

A study by Zelenitsky and colleagues evaluated the efficacy of 3 ciprofloxacin dosing regimens using Monte Carlo simulations (400 mg IV every 12 hours [standard dose], 400 mg IV every 8 hours [high dose], and a PD-targeted regimen dosed to attain an fAUC/MIC value > 86).³ An fAUC/MIC value of 86 was previously determined to predict cure rates of at least 90%.⁴ The Clinical and Laboratory Standards Institute defines a P aeruginosa MIC of ≤ 1 μg/mL to be susceptible and an MIC of ≥ 4 μg/mL to be resistant to ciprofloxacin.⁵

The researchers determined PTA and POC values for each regimen based on various MICs. The in vitro laboratory simulations revealed the PTA and POC values approached 100% for all 3 regimens when the MIC was 0.125 μg/mL. However, when the MIC was 1 μg/mL, the PTA for the standard and high dose was 0%, and the PD-targeted regimen was 40%. The POC was 27%, 40%, and 72% for the standard dose, high dose, and the PD-targeted regimen, respectively. Although the PD-targeted regimen was the most efficacious, it took doses exceeding 1,300 mg and 1,800 mg daily to achieve similar results. In addition, PD-targeted regimens are not practical for dosing due to patient variability in CrCl. From these simulations, it was concluded that the high dose of ciprofloxacin 400 mg IV every 8 hours should be recommended for treating Pseudomonas infections in patients with normal renal function.

Related: Antimicrobial Stewardship in an Outpatient Parenteral Antibiotic Therapy Program

In another study by Lodise and colleagues, researchers examined the clinical implications of an extended-infusion dosing strategy for piperacillin-tazobactam in the critically ill.⁶ The 2 piperacillin- tazobactam regimens evaluated were 3.375 g IV over 30 minutes given every 4 or 6 hours and 3.375 g IV over 4 hours given every 8 hours. The 14-day mortality rate in critically ill patients who received the extended- and intermittent-infusion regimens was 12.2% and 31.6%, respectively (P = .04). Additionally, patients receiving the extended-infusion regimen had a decreased in-house length of stay compared with the intermittent-infusion group (21 vs 38 days, P = .02). Despite having a lower drug concentration peak, the extended-infusion regimen maintains steady drug concentrations above the MIC for a greater period, resulting in prolonged therapeutic efficacy. Other antibiotics (cefepime⁷ and ceftazidime⁸) have been studied by using the same methodology of comparing intermittent and extended infusions and have had similar results.

Given the management challenges associated with P aeruginosa infections, it is important for clinicians to recognize patients who may have or be at risk of infection with P aeruginosa and use appropriate dosing regimens to effectively manage infections and improve patient outcomes.

Additional Note
An earlier version of this article appeared in the Pharmacy Related Newsletter: The Capsule, of the William S. Middleton Memorial Veterans Hospital.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.