Clinical Edge Journal Scan Commentary: Breast Cancer January 2022

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Dr. Roesch scans the journals, so you don't have to!

Erin Roesch, MD
The role of adjuvant chemotherapy in addition to endocrine therapy for hormone-receptor positive (HR+) early breast cancer has been studied in prospective trials utilizing genomic assays. The RxPONDER trial included 5,083 women with HR+/HER2-negative breast cancer, 1-3 nodes involved and RS ≤25, and randomized to endocrine therapy alone or chemoendocrine therapy (Kalinsky et al). Premenopausal women were found to have improved 5-year invasive disease-free survival (iDFS) and distant relapse-free survival (DRFS) with the addition of chemotherapy; IDFS 89.0% vs 93.9% (HR 0.60, P = 0.002) and DRFS 92.8% vs 96.1% (HR 0.58, P = 0.009) for endocrine group vs chemoendocrine group, respectively. A remaining question is whether the impact of chemotherapy in premenopausal women is related to direct cytotoxic effect or treatment-induced amenorrhea. The benefit of ovarian suppression plus an aromatase inhibitor in premenopausal patients at high recurrence risk was shown in TEXT/SOFT trials, and studies are needed to elucidate whether chemotherapy can be replaced by more effective endocrine therapy in select populations.


Oocyte and embryo cryopreservation are standard fertility preservation techniques, and gonadotropin-releasing hormone agonist (GnRHa) administration during chemotherapy is another strategy to preserve ovarian function. The phase 3 POEMS/S0230 study demonstrated higher pregnancy rates (5-year cumulative incidence 23.1% vs 12.2%, P = 0.03) among premenopausal patients with HR-negative early breast cancer who received GnRHa (goserelin) during chemotherapy vs chemotherapy alone. Furthermore, there was a trend towards improvement in survival outcomes with GnRHa + chemotherapy. Hypothetical concerns have existed regarding the safety of this approach, particularly in HR+ breast cancer. The PROMISE-GIM6 trial randomized 281 patients to receive chemotherapy alone or with GnRHa triptorelin (Lambertini et al) and found no difference in disease-free survival (DFS) or overall survival (OS) between GnRHa vs control groups (12-year DFS 65.7% vs 69.2%, HR 1.16; 12-year OS 81.2% vs 81.3%, HR 1.17). In patients with HR+ disease (80.4%), HR for DFS and OS was 1.02 and 1.12, respectively. The 12-year cumulative incidence of pregnancy was also higher in the GnRHa vs control group (6.5% vs 3.2%). These studies suggest no detrimental effect of GnRHa use during chemotherapy on long-term outcomes, including patients with HR+ disease, and support its role in ovarian protection.

COVID-19 has had various implications on breast cancer care, reflecting institutional policies, resources and patient preferences and potential concerns during the pandemic. A retrospective chart review of patients diagnosed at Mayo Clinic Rochester with a new breast cancer during vs pre-COVID-19, examined trends in diagnosis and treatment approaches during these times (Tonneson et al). Among 573 patients, there was no significant difference in clinical prognostic stage, although a slightly higher percentage of patients who presented with stage II-IV disease during COVID-19 vs pre-COVID-19 (29% vs 26%, P = 0.42). The use of neoadjuvant endocrine therapy (NET) significantly increased during COVID-19, and notably in patients with HR+/HER2- breast cancer (10% pre-COVID-19 vs 23% during COVID-19 (P = 0.001)) with a significant increase in stage I patients (7% vs 22%, P < 0.001). Various societies provided language to support neoadjuvant therapy as a bridge to surgical intervention during COVID-19 in the appropriate clinical scenarios. Extended follow-up of studies examining approaches utilized during the pandemic are desired to further define long-term impact on outcomes.

A pooled analysis of the PALOMA trials demonstrated progression-free survival benefit with palbociclib + endocrine therapy vs endocrine therapy alone in patients ≥65 years, and although myelosuppression was more common in patients ≥75 years, the combination remained well-tolerated. Ismail et al described real-world experience of palbociclib in older patients with advanced HR+ breast cancer. Among 598 patients, palbociclib dose reductions occurred in 33%, and those requiring a dose reduction were older vs those without dose reduction (median age 67 vs 63 years, P = 0.004). Despite higher frequency of dose reductions in older patients, this did not appear to compromise outcomes; time to next treatment was significantly longer (16.9 vs 11.6 months, P = 0.013) than younger patients but OS was similar (20.7 vs 26.7 months, P = 0.051). Although older patients may be at higher risk of toxicities due to co-morbidities or performance status limitations, palbociclib remains a valuable therapeutic option combined with endocrine therapy for advanced HR+/HER2- breast cancer.

References:


Francis PA, Pagani O, Fleming GF, et al; SOFT and TEXT Investigators and the International Breast Cancer Study Group. Tailoring adjuvant endocrine therapy for premenopausal breast cancer. N Engl J Med. 2018;379(2):122-137.

Moore HCF, Unger JM, Phillips K-A, et al. Final analysis of the prevention of early menopause study (POEMS)/SWOG Intergroup S0230. J Natl Cancer Inst. 2019;111(2):210–213.

Dietz JR, Moran MS, Isakoff SJ, et al. Recommendations for prioritization, treatment, and triage of breast cancer patients during the COVID-19 pandemic. The COVID-19 pandemic breast cancer consortium. Breast Cancer Res Treat. 2020;181(3):487–97.

Rugo HS, Turner NC, Finn RS, et al. Palbociclib plus endocrine therapy in older women with HR+/HER2- advanced breast cancer: a pooled analysis of randomised PALOMA clinical studies. Eur J Cancer. 2018;101:123e33.

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Erin E. Roesch, MD, Associate Staff, Department of Medical Oncology, Cleveland Clinic, Cleveland, Ohio
Erin E. Roesch, MD, has disclosed the following relevant financial relationships:
Serve(d) as a speaker or a member of a speakers bureau for: Puma Biotechnology

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Erin E. Roesch, MD, Associate Staff, Department of Medical Oncology, Cleveland Clinic, Cleveland, Ohio
Erin E. Roesch, MD, has disclosed the following relevant financial relationships:
Serve(d) as a speaker or a member of a speakers bureau for: Puma Biotechnology

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Erin E. Roesch, MD, Associate Staff, Department of Medical Oncology, Cleveland Clinic, Cleveland, Ohio
Erin E. Roesch, MD, has disclosed the following relevant financial relationships:
Serve(d) as a speaker or a member of a speakers bureau for: Puma Biotechnology

Dr. Roesch scans the journals, so you don't have to!
Dr. Roesch scans the journals, so you don't have to!

Erin Roesch, MD
The role of adjuvant chemotherapy in addition to endocrine therapy for hormone-receptor positive (HR+) early breast cancer has been studied in prospective trials utilizing genomic assays. The RxPONDER trial included 5,083 women with HR+/HER2-negative breast cancer, 1-3 nodes involved and RS ≤25, and randomized to endocrine therapy alone or chemoendocrine therapy (Kalinsky et al). Premenopausal women were found to have improved 5-year invasive disease-free survival (iDFS) and distant relapse-free survival (DRFS) with the addition of chemotherapy; IDFS 89.0% vs 93.9% (HR 0.60, P = 0.002) and DRFS 92.8% vs 96.1% (HR 0.58, P = 0.009) for endocrine group vs chemoendocrine group, respectively. A remaining question is whether the impact of chemotherapy in premenopausal women is related to direct cytotoxic effect or treatment-induced amenorrhea. The benefit of ovarian suppression plus an aromatase inhibitor in premenopausal patients at high recurrence risk was shown in TEXT/SOFT trials, and studies are needed to elucidate whether chemotherapy can be replaced by more effective endocrine therapy in select populations.


Oocyte and embryo cryopreservation are standard fertility preservation techniques, and gonadotropin-releasing hormone agonist (GnRHa) administration during chemotherapy is another strategy to preserve ovarian function. The phase 3 POEMS/S0230 study demonstrated higher pregnancy rates (5-year cumulative incidence 23.1% vs 12.2%, P = 0.03) among premenopausal patients with HR-negative early breast cancer who received GnRHa (goserelin) during chemotherapy vs chemotherapy alone. Furthermore, there was a trend towards improvement in survival outcomes with GnRHa + chemotherapy. Hypothetical concerns have existed regarding the safety of this approach, particularly in HR+ breast cancer. The PROMISE-GIM6 trial randomized 281 patients to receive chemotherapy alone or with GnRHa triptorelin (Lambertini et al) and found no difference in disease-free survival (DFS) or overall survival (OS) between GnRHa vs control groups (12-year DFS 65.7% vs 69.2%, HR 1.16; 12-year OS 81.2% vs 81.3%, HR 1.17). In patients with HR+ disease (80.4%), HR for DFS and OS was 1.02 and 1.12, respectively. The 12-year cumulative incidence of pregnancy was also higher in the GnRHa vs control group (6.5% vs 3.2%). These studies suggest no detrimental effect of GnRHa use during chemotherapy on long-term outcomes, including patients with HR+ disease, and support its role in ovarian protection.

COVID-19 has had various implications on breast cancer care, reflecting institutional policies, resources and patient preferences and potential concerns during the pandemic. A retrospective chart review of patients diagnosed at Mayo Clinic Rochester with a new breast cancer during vs pre-COVID-19, examined trends in diagnosis and treatment approaches during these times (Tonneson et al). Among 573 patients, there was no significant difference in clinical prognostic stage, although a slightly higher percentage of patients who presented with stage II-IV disease during COVID-19 vs pre-COVID-19 (29% vs 26%, P = 0.42). The use of neoadjuvant endocrine therapy (NET) significantly increased during COVID-19, and notably in patients with HR+/HER2- breast cancer (10% pre-COVID-19 vs 23% during COVID-19 (P = 0.001)) with a significant increase in stage I patients (7% vs 22%, P < 0.001). Various societies provided language to support neoadjuvant therapy as a bridge to surgical intervention during COVID-19 in the appropriate clinical scenarios. Extended follow-up of studies examining approaches utilized during the pandemic are desired to further define long-term impact on outcomes.

A pooled analysis of the PALOMA trials demonstrated progression-free survival benefit with palbociclib + endocrine therapy vs endocrine therapy alone in patients ≥65 years, and although myelosuppression was more common in patients ≥75 years, the combination remained well-tolerated. Ismail et al described real-world experience of palbociclib in older patients with advanced HR+ breast cancer. Among 598 patients, palbociclib dose reductions occurred in 33%, and those requiring a dose reduction were older vs those without dose reduction (median age 67 vs 63 years, P = 0.004). Despite higher frequency of dose reductions in older patients, this did not appear to compromise outcomes; time to next treatment was significantly longer (16.9 vs 11.6 months, P = 0.013) than younger patients but OS was similar (20.7 vs 26.7 months, P = 0.051). Although older patients may be at higher risk of toxicities due to co-morbidities or performance status limitations, palbociclib remains a valuable therapeutic option combined with endocrine therapy for advanced HR+/HER2- breast cancer.

References:


Francis PA, Pagani O, Fleming GF, et al; SOFT and TEXT Investigators and the International Breast Cancer Study Group. Tailoring adjuvant endocrine therapy for premenopausal breast cancer. N Engl J Med. 2018;379(2):122-137.

Moore HCF, Unger JM, Phillips K-A, et al. Final analysis of the prevention of early menopause study (POEMS)/SWOG Intergroup S0230. J Natl Cancer Inst. 2019;111(2):210–213.

Dietz JR, Moran MS, Isakoff SJ, et al. Recommendations for prioritization, treatment, and triage of breast cancer patients during the COVID-19 pandemic. The COVID-19 pandemic breast cancer consortium. Breast Cancer Res Treat. 2020;181(3):487–97.

Rugo HS, Turner NC, Finn RS, et al. Palbociclib plus endocrine therapy in older women with HR+/HER2- advanced breast cancer: a pooled analysis of randomised PALOMA clinical studies. Eur J Cancer. 2018;101:123e33.

Erin Roesch, MD
The role of adjuvant chemotherapy in addition to endocrine therapy for hormone-receptor positive (HR+) early breast cancer has been studied in prospective trials utilizing genomic assays. The RxPONDER trial included 5,083 women with HR+/HER2-negative breast cancer, 1-3 nodes involved and RS ≤25, and randomized to endocrine therapy alone or chemoendocrine therapy (Kalinsky et al). Premenopausal women were found to have improved 5-year invasive disease-free survival (iDFS) and distant relapse-free survival (DRFS) with the addition of chemotherapy; IDFS 89.0% vs 93.9% (HR 0.60, P = 0.002) and DRFS 92.8% vs 96.1% (HR 0.58, P = 0.009) for endocrine group vs chemoendocrine group, respectively. A remaining question is whether the impact of chemotherapy in premenopausal women is related to direct cytotoxic effect or treatment-induced amenorrhea. The benefit of ovarian suppression plus an aromatase inhibitor in premenopausal patients at high recurrence risk was shown in TEXT/SOFT trials, and studies are needed to elucidate whether chemotherapy can be replaced by more effective endocrine therapy in select populations.


Oocyte and embryo cryopreservation are standard fertility preservation techniques, and gonadotropin-releasing hormone agonist (GnRHa) administration during chemotherapy is another strategy to preserve ovarian function. The phase 3 POEMS/S0230 study demonstrated higher pregnancy rates (5-year cumulative incidence 23.1% vs 12.2%, P = 0.03) among premenopausal patients with HR-negative early breast cancer who received GnRHa (goserelin) during chemotherapy vs chemotherapy alone. Furthermore, there was a trend towards improvement in survival outcomes with GnRHa + chemotherapy. Hypothetical concerns have existed regarding the safety of this approach, particularly in HR+ breast cancer. The PROMISE-GIM6 trial randomized 281 patients to receive chemotherapy alone or with GnRHa triptorelin (Lambertini et al) and found no difference in disease-free survival (DFS) or overall survival (OS) between GnRHa vs control groups (12-year DFS 65.7% vs 69.2%, HR 1.16; 12-year OS 81.2% vs 81.3%, HR 1.17). In patients with HR+ disease (80.4%), HR for DFS and OS was 1.02 and 1.12, respectively. The 12-year cumulative incidence of pregnancy was also higher in the GnRHa vs control group (6.5% vs 3.2%). These studies suggest no detrimental effect of GnRHa use during chemotherapy on long-term outcomes, including patients with HR+ disease, and support its role in ovarian protection.

COVID-19 has had various implications on breast cancer care, reflecting institutional policies, resources and patient preferences and potential concerns during the pandemic. A retrospective chart review of patients diagnosed at Mayo Clinic Rochester with a new breast cancer during vs pre-COVID-19, examined trends in diagnosis and treatment approaches during these times (Tonneson et al). Among 573 patients, there was no significant difference in clinical prognostic stage, although a slightly higher percentage of patients who presented with stage II-IV disease during COVID-19 vs pre-COVID-19 (29% vs 26%, P = 0.42). The use of neoadjuvant endocrine therapy (NET) significantly increased during COVID-19, and notably in patients with HR+/HER2- breast cancer (10% pre-COVID-19 vs 23% during COVID-19 (P = 0.001)) with a significant increase in stage I patients (7% vs 22%, P < 0.001). Various societies provided language to support neoadjuvant therapy as a bridge to surgical intervention during COVID-19 in the appropriate clinical scenarios. Extended follow-up of studies examining approaches utilized during the pandemic are desired to further define long-term impact on outcomes.

A pooled analysis of the PALOMA trials demonstrated progression-free survival benefit with palbociclib + endocrine therapy vs endocrine therapy alone in patients ≥65 years, and although myelosuppression was more common in patients ≥75 years, the combination remained well-tolerated. Ismail et al described real-world experience of palbociclib in older patients with advanced HR+ breast cancer. Among 598 patients, palbociclib dose reductions occurred in 33%, and those requiring a dose reduction were older vs those without dose reduction (median age 67 vs 63 years, P = 0.004). Despite higher frequency of dose reductions in older patients, this did not appear to compromise outcomes; time to next treatment was significantly longer (16.9 vs 11.6 months, P = 0.013) than younger patients but OS was similar (20.7 vs 26.7 months, P = 0.051). Although older patients may be at higher risk of toxicities due to co-morbidities or performance status limitations, palbociclib remains a valuable therapeutic option combined with endocrine therapy for advanced HR+/HER2- breast cancer.

References:


Francis PA, Pagani O, Fleming GF, et al; SOFT and TEXT Investigators and the International Breast Cancer Study Group. Tailoring adjuvant endocrine therapy for premenopausal breast cancer. N Engl J Med. 2018;379(2):122-137.

Moore HCF, Unger JM, Phillips K-A, et al. Final analysis of the prevention of early menopause study (POEMS)/SWOG Intergroup S0230. J Natl Cancer Inst. 2019;111(2):210–213.

Dietz JR, Moran MS, Isakoff SJ, et al. Recommendations for prioritization, treatment, and triage of breast cancer patients during the COVID-19 pandemic. The COVID-19 pandemic breast cancer consortium. Breast Cancer Res Treat. 2020;181(3):487–97.

Rugo HS, Turner NC, Finn RS, et al. Palbociclib plus endocrine therapy in older women with HR+/HER2- advanced breast cancer: a pooled analysis of randomised PALOMA clinical studies. Eur J Cancer. 2018;101:123e33.

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Not all patients with community-acquired pneumonia respond to adjunctive dexamethasone

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Key clinical point: Neutrophil count, white blood cell (WBC) count, or neutrophil-lymphocyte ratio (NLR) may help in ascertaining which patients hospitalized for community-acquired pneumonia (CAP) would benefit from adjunctive oral dexamethasone therapy.

Main finding: Among patients with a high neutrophil count, WBC count, or NLR who did not die in hospital, those who received dexamethasone had a shorter median length of stay (LOS) than those who received placebo (4 days vs. 6 days), whereas patients with low values for these parameters showed no difference in LOS between those receiving placebo and dexamethasone (P < .05).

Study details: Findings are from a post hoc analysis on 354 out of the 401 non-ICU patients with CAP included in the randomized placebo-controlled Santeon-CAP trial who were randomly assigned to receive either placebo or oral dexamethasone.

Disclosures: The study was sponsored by St. Antonius research fund. The authors declared no conflicts of interests.

Source: Wittermans E et al. Eur J Intern Med. 2021 (Nov 12). Doi: 10.1016/j.ejim.2021.10.030.

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Key clinical point: Neutrophil count, white blood cell (WBC) count, or neutrophil-lymphocyte ratio (NLR) may help in ascertaining which patients hospitalized for community-acquired pneumonia (CAP) would benefit from adjunctive oral dexamethasone therapy.

Main finding: Among patients with a high neutrophil count, WBC count, or NLR who did not die in hospital, those who received dexamethasone had a shorter median length of stay (LOS) than those who received placebo (4 days vs. 6 days), whereas patients with low values for these parameters showed no difference in LOS between those receiving placebo and dexamethasone (P < .05).

Study details: Findings are from a post hoc analysis on 354 out of the 401 non-ICU patients with CAP included in the randomized placebo-controlled Santeon-CAP trial who were randomly assigned to receive either placebo or oral dexamethasone.

Disclosures: The study was sponsored by St. Antonius research fund. The authors declared no conflicts of interests.

Source: Wittermans E et al. Eur J Intern Med. 2021 (Nov 12). Doi: 10.1016/j.ejim.2021.10.030.

Key clinical point: Neutrophil count, white blood cell (WBC) count, or neutrophil-lymphocyte ratio (NLR) may help in ascertaining which patients hospitalized for community-acquired pneumonia (CAP) would benefit from adjunctive oral dexamethasone therapy.

Main finding: Among patients with a high neutrophil count, WBC count, or NLR who did not die in hospital, those who received dexamethasone had a shorter median length of stay (LOS) than those who received placebo (4 days vs. 6 days), whereas patients with low values for these parameters showed no difference in LOS between those receiving placebo and dexamethasone (P < .05).

Study details: Findings are from a post hoc analysis on 354 out of the 401 non-ICU patients with CAP included in the randomized placebo-controlled Santeon-CAP trial who were randomly assigned to receive either placebo or oral dexamethasone.

Disclosures: The study was sponsored by St. Antonius research fund. The authors declared no conflicts of interests.

Source: Wittermans E et al. Eur J Intern Med. 2021 (Nov 12). Doi: 10.1016/j.ejim.2021.10.030.

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Serum IL-17 may aid in predicting the prognosis of community-acquired pneumonia

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Key clinical point: Serum IL-17 levels show a positive correlation with the severity and poor prognostic outcomes in patients with community-acquired pneumonia (CAP).

Main finding: In patients with CAP, serum IL-17 levels at admission increased in parallel with CAP severity scores, such as pneumonia severity index, and, after adjusting for confounding factors, showed a positive correlation with intensive care unit (ICU) admission (adjusted odds ratio [aOR] 1.01; P = .01), mechanical ventilation (aOR 1.10; P = .02), death (aOR, 1.05; P < .01), and hospital stay of 14 days or more (aOR 1.21; P = .01).

Study details: This was a prospective cohort study including 239 patients who were hospitalized for CAP.

Disclosures: The National Natural Science Foundation of China, Anhui Provincial Natural Science Foundation, National Natural Science Foundation Incubation Program of the Second Affiliated Hospital of Anhui Medical University, and Scientific Research of Health Commission in Anhui Province sponsored the study. None of the authors declared any conflict of interests.

Source: Feng CM et al. BMC Pulm Med. 2021;21:393 (Dec 2). Doi: 10.1186/s12890-021-01770-6.

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Key clinical point: Serum IL-17 levels show a positive correlation with the severity and poor prognostic outcomes in patients with community-acquired pneumonia (CAP).

Main finding: In patients with CAP, serum IL-17 levels at admission increased in parallel with CAP severity scores, such as pneumonia severity index, and, after adjusting for confounding factors, showed a positive correlation with intensive care unit (ICU) admission (adjusted odds ratio [aOR] 1.01; P = .01), mechanical ventilation (aOR 1.10; P = .02), death (aOR, 1.05; P < .01), and hospital stay of 14 days or more (aOR 1.21; P = .01).

Study details: This was a prospective cohort study including 239 patients who were hospitalized for CAP.

Disclosures: The National Natural Science Foundation of China, Anhui Provincial Natural Science Foundation, National Natural Science Foundation Incubation Program of the Second Affiliated Hospital of Anhui Medical University, and Scientific Research of Health Commission in Anhui Province sponsored the study. None of the authors declared any conflict of interests.

Source: Feng CM et al. BMC Pulm Med. 2021;21:393 (Dec 2). Doi: 10.1186/s12890-021-01770-6.

Key clinical point: Serum IL-17 levels show a positive correlation with the severity and poor prognostic outcomes in patients with community-acquired pneumonia (CAP).

Main finding: In patients with CAP, serum IL-17 levels at admission increased in parallel with CAP severity scores, such as pneumonia severity index, and, after adjusting for confounding factors, showed a positive correlation with intensive care unit (ICU) admission (adjusted odds ratio [aOR] 1.01; P = .01), mechanical ventilation (aOR 1.10; P = .02), death (aOR, 1.05; P < .01), and hospital stay of 14 days or more (aOR 1.21; P = .01).

Study details: This was a prospective cohort study including 239 patients who were hospitalized for CAP.

Disclosures: The National Natural Science Foundation of China, Anhui Provincial Natural Science Foundation, National Natural Science Foundation Incubation Program of the Second Affiliated Hospital of Anhui Medical University, and Scientific Research of Health Commission in Anhui Province sponsored the study. None of the authors declared any conflict of interests.

Source: Feng CM et al. BMC Pulm Med. 2021;21:393 (Dec 2). Doi: 10.1186/s12890-021-01770-6.

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Antibiotics posing minimal AKI risk in community-acquired pneumonia

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Key clinical point: In patients hospitalized for community-acquired pneumonia (CAP), the least risk of acute kidney injury (AKI) can be achieved by empiric treatment with a third-generation cephalosporin ± macrolide or a respiratory fluoroquinolone.

Main finding: Barring fluoroquinolones (adjusted odds ratio [aOR] 1.06; 95% CI 0.98-1.14), all regimens offered a higher risk for AKI than a third-generation cephalosporin ± macrolide, with piperacillin/tazobactam + vancomycin being associated with the highest AKI odds (aOR 1.89; 95% CI 1.73-2.06).

Study details: Findings are from a retrospective cohort study consisting of 449,535 adult patients hospitalized for CAP, of whom 3.1% developed AKI.

Disclosures: The study was sponsored by the Agency for Healthcare Research and Quality. The authors declared no conflict of interests.

Source: Le P et al. Curr Med Res Opin. 2021 (Nov 15). Doi: 10.1080/03007995.2021.2000716.

 

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Key clinical point: In patients hospitalized for community-acquired pneumonia (CAP), the least risk of acute kidney injury (AKI) can be achieved by empiric treatment with a third-generation cephalosporin ± macrolide or a respiratory fluoroquinolone.

Main finding: Barring fluoroquinolones (adjusted odds ratio [aOR] 1.06; 95% CI 0.98-1.14), all regimens offered a higher risk for AKI than a third-generation cephalosporin ± macrolide, with piperacillin/tazobactam + vancomycin being associated with the highest AKI odds (aOR 1.89; 95% CI 1.73-2.06).

Study details: Findings are from a retrospective cohort study consisting of 449,535 adult patients hospitalized for CAP, of whom 3.1% developed AKI.

Disclosures: The study was sponsored by the Agency for Healthcare Research and Quality. The authors declared no conflict of interests.

Source: Le P et al. Curr Med Res Opin. 2021 (Nov 15). Doi: 10.1080/03007995.2021.2000716.

 

Key clinical point: In patients hospitalized for community-acquired pneumonia (CAP), the least risk of acute kidney injury (AKI) can be achieved by empiric treatment with a third-generation cephalosporin ± macrolide or a respiratory fluoroquinolone.

Main finding: Barring fluoroquinolones (adjusted odds ratio [aOR] 1.06; 95% CI 0.98-1.14), all regimens offered a higher risk for AKI than a third-generation cephalosporin ± macrolide, with piperacillin/tazobactam + vancomycin being associated with the highest AKI odds (aOR 1.89; 95% CI 1.73-2.06).

Study details: Findings are from a retrospective cohort study consisting of 449,535 adult patients hospitalized for CAP, of whom 3.1% developed AKI.

Disclosures: The study was sponsored by the Agency for Healthcare Research and Quality. The authors declared no conflict of interests.

Source: Le P et al. Curr Med Res Opin. 2021 (Nov 15). Doi: 10.1080/03007995.2021.2000716.

 

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How reliable is qSOFA in predicting mortality in community-acquired pneumonia?

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Key clinical point: Quick sequential (sepsis-related) organ failure assessment (qSOFA) is better than the Infectious Disease Society of America/American Thoracic Society minor criteria and worse than confusion, urea, respiratory rate, blood pressure, and age ≥ 65 years (CURB-65) in predicting mortality in community-acquired pneumonia (CAP).

 

Main finding: The predictive validity of qSOFA for mortality (area under the receiver operating characteristic curve [AUROC] 0.868; 95% CI 0.853-0.882) was higher than that of minor criteria (AUROC 0.824; P < .0001) and lower than that of CURB-65 (AUROC 0.919; P < .0001).

Study details: The data come from an observational prospective cohort study consisting of 2,116 adult patients with CAP.

Disclosures: The study was sponsored by the Medical Science and Technology Foundation of Guangdong Province, Planned Science and Technology Project of Shenzhen Municipality, and Nonprofit Scientific Research Project of Futian District. The authors declared no conflict of interests.

Source: Guo Q et al. Am J Emerg Med. 2022(Feb);52:1-7 (Nov 24). Doi: 10.1016/j.ajem.2021.11.029.

 

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Key clinical point: Quick sequential (sepsis-related) organ failure assessment (qSOFA) is better than the Infectious Disease Society of America/American Thoracic Society minor criteria and worse than confusion, urea, respiratory rate, blood pressure, and age ≥ 65 years (CURB-65) in predicting mortality in community-acquired pneumonia (CAP).

 

Main finding: The predictive validity of qSOFA for mortality (area under the receiver operating characteristic curve [AUROC] 0.868; 95% CI 0.853-0.882) was higher than that of minor criteria (AUROC 0.824; P < .0001) and lower than that of CURB-65 (AUROC 0.919; P < .0001).

Study details: The data come from an observational prospective cohort study consisting of 2,116 adult patients with CAP.

Disclosures: The study was sponsored by the Medical Science and Technology Foundation of Guangdong Province, Planned Science and Technology Project of Shenzhen Municipality, and Nonprofit Scientific Research Project of Futian District. The authors declared no conflict of interests.

Source: Guo Q et al. Am J Emerg Med. 2022(Feb);52:1-7 (Nov 24). Doi: 10.1016/j.ajem.2021.11.029.

 

Key clinical point: Quick sequential (sepsis-related) organ failure assessment (qSOFA) is better than the Infectious Disease Society of America/American Thoracic Society minor criteria and worse than confusion, urea, respiratory rate, blood pressure, and age ≥ 65 years (CURB-65) in predicting mortality in community-acquired pneumonia (CAP).

 

Main finding: The predictive validity of qSOFA for mortality (area under the receiver operating characteristic curve [AUROC] 0.868; 95% CI 0.853-0.882) was higher than that of minor criteria (AUROC 0.824; P < .0001) and lower than that of CURB-65 (AUROC 0.919; P < .0001).

Study details: The data come from an observational prospective cohort study consisting of 2,116 adult patients with CAP.

Disclosures: The study was sponsored by the Medical Science and Technology Foundation of Guangdong Province, Planned Science and Technology Project of Shenzhen Municipality, and Nonprofit Scientific Research Project of Futian District. The authors declared no conflict of interests.

Source: Guo Q et al. Am J Emerg Med. 2022(Feb);52:1-7 (Nov 24). Doi: 10.1016/j.ajem.2021.11.029.

 

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Mortality in community-acquired pneumonia is related to admission blood glucose levels

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Key clinical point: A positive association exists between blood glucose levels at hospital admission for community-acquired pneumonia (CAP) and 28-day mortality, and the strength of this association decreases with age.

Main finding: After adjusting for confounding factors, all patients exhibited a significant association between blood glucose levels at hospitalization and 28-day mortality (hazard ratio [HR] 2.08; P < .01). After age stratification, this association was evidenced in both middle-aged (HR 4.48; P < .01) and elderly (HR 1.52; P = .05) patients, but was stronger in the former (P = .01).

Study details: This was a retrospective observational study including 1,656 patients aged 45 years who were hospitalized for CAP, of which 592 were middle-aged (45-64 years) and 1,064 were elderly (>65 years).

Disclosures: The authors declared no conflict of interests.

Source: Shen Y et al. Int J Gen Med. 2021;14:7775-7781 (Nov 6). Doi: 10.2147/IJGM.S331082.

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Key clinical point: A positive association exists between blood glucose levels at hospital admission for community-acquired pneumonia (CAP) and 28-day mortality, and the strength of this association decreases with age.

Main finding: After adjusting for confounding factors, all patients exhibited a significant association between blood glucose levels at hospitalization and 28-day mortality (hazard ratio [HR] 2.08; P < .01). After age stratification, this association was evidenced in both middle-aged (HR 4.48; P < .01) and elderly (HR 1.52; P = .05) patients, but was stronger in the former (P = .01).

Study details: This was a retrospective observational study including 1,656 patients aged 45 years who were hospitalized for CAP, of which 592 were middle-aged (45-64 years) and 1,064 were elderly (>65 years).

Disclosures: The authors declared no conflict of interests.

Source: Shen Y et al. Int J Gen Med. 2021;14:7775-7781 (Nov 6). Doi: 10.2147/IJGM.S331082.

Key clinical point: A positive association exists between blood glucose levels at hospital admission for community-acquired pneumonia (CAP) and 28-day mortality, and the strength of this association decreases with age.

Main finding: After adjusting for confounding factors, all patients exhibited a significant association between blood glucose levels at hospitalization and 28-day mortality (hazard ratio [HR] 2.08; P < .01). After age stratification, this association was evidenced in both middle-aged (HR 4.48; P < .01) and elderly (HR 1.52; P = .05) patients, but was stronger in the former (P = .01).

Study details: This was a retrospective observational study including 1,656 patients aged 45 years who were hospitalized for CAP, of which 592 were middle-aged (45-64 years) and 1,064 were elderly (>65 years).

Disclosures: The authors declared no conflict of interests.

Source: Shen Y et al. Int J Gen Med. 2021;14:7775-7781 (Nov 6). Doi: 10.2147/IJGM.S331082.

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Most community-acquired bacterial pneumonia-causing pathogens succumb to lefamulin

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Key clinical point: Lefamulin is suitable as monotherapy against common community-acquired bacterial pneumonia (CABP)-causing pathogens, both typical and atypical, including drug-resistant strains and those causing polymicrobial infections.

Main finding: Lefamulin was as effective as moxifloxacin in the microbiological intent-to-treat (microITT) population, exhibiting a similar early clinical response rate (89.3% vs. 93.0%; difference ‒3.7; 95% CI ‒7.9 to 0.5) and investigator assessment of clinical response success rate (83.2% vs. 86.7%; difference ‒3.3; 95% CI ‒8.6 to 2.0).

Study details: The study analyzed pooled data from the phase 3 noninferiority Lefamulin Evaluation Against Pneumonia 1 and 2 trials, including a total of 1,289 adult patients with CABP (Pneumonia Outcomes Research Team risk classes II-V) who were randomly assigned to receive lefamulin or moxifloxacin. Of these, a baseline CABP pathogen was detected in 709 patients (microITT population).

Disclosures: Nabriva Therapeutics plc (Fort Washington, PA, USA) sponsored the study. Some of the authors, including the lead author, are former or current employees of or stockholders in Nabriva Therapeutics. A few others received research grants/consultation fees from various sources including Nabriva Therapeutics.

Source: Paukner S et al. J Glob Antimicrob Resist. 2021 (Nov 14). Doi: 10.1016/j.jgar.2021.10.021.

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Key clinical point: Lefamulin is suitable as monotherapy against common community-acquired bacterial pneumonia (CABP)-causing pathogens, both typical and atypical, including drug-resistant strains and those causing polymicrobial infections.

Main finding: Lefamulin was as effective as moxifloxacin in the microbiological intent-to-treat (microITT) population, exhibiting a similar early clinical response rate (89.3% vs. 93.0%; difference ‒3.7; 95% CI ‒7.9 to 0.5) and investigator assessment of clinical response success rate (83.2% vs. 86.7%; difference ‒3.3; 95% CI ‒8.6 to 2.0).

Study details: The study analyzed pooled data from the phase 3 noninferiority Lefamulin Evaluation Against Pneumonia 1 and 2 trials, including a total of 1,289 adult patients with CABP (Pneumonia Outcomes Research Team risk classes II-V) who were randomly assigned to receive lefamulin or moxifloxacin. Of these, a baseline CABP pathogen was detected in 709 patients (microITT population).

Disclosures: Nabriva Therapeutics plc (Fort Washington, PA, USA) sponsored the study. Some of the authors, including the lead author, are former or current employees of or stockholders in Nabriva Therapeutics. A few others received research grants/consultation fees from various sources including Nabriva Therapeutics.

Source: Paukner S et al. J Glob Antimicrob Resist. 2021 (Nov 14). Doi: 10.1016/j.jgar.2021.10.021.

Key clinical point: Lefamulin is suitable as monotherapy against common community-acquired bacterial pneumonia (CABP)-causing pathogens, both typical and atypical, including drug-resistant strains and those causing polymicrobial infections.

Main finding: Lefamulin was as effective as moxifloxacin in the microbiological intent-to-treat (microITT) population, exhibiting a similar early clinical response rate (89.3% vs. 93.0%; difference ‒3.7; 95% CI ‒7.9 to 0.5) and investigator assessment of clinical response success rate (83.2% vs. 86.7%; difference ‒3.3; 95% CI ‒8.6 to 2.0).

Study details: The study analyzed pooled data from the phase 3 noninferiority Lefamulin Evaluation Against Pneumonia 1 and 2 trials, including a total of 1,289 adult patients with CABP (Pneumonia Outcomes Research Team risk classes II-V) who were randomly assigned to receive lefamulin or moxifloxacin. Of these, a baseline CABP pathogen was detected in 709 patients (microITT population).

Disclosures: Nabriva Therapeutics plc (Fort Washington, PA, USA) sponsored the study. Some of the authors, including the lead author, are former or current employees of or stockholders in Nabriva Therapeutics. A few others received research grants/consultation fees from various sources including Nabriva Therapeutics.

Source: Paukner S et al. J Glob Antimicrob Resist. 2021 (Nov 14). Doi: 10.1016/j.jgar.2021.10.021.

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Collaborative stewardship steers appropriate antibiotic use against uncomplicated community-acquired pneumonia

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Key clinical point: Reinforcement of antibiotic stewardship by forming large multihospital collaboratives increases adherence to the appropriate 5-day therapy for uncomplicated community-acquired pneumonia (CAP) while decreasing adverse events.

Main finding: After adjusting for hospital clustering, the 20.9% predicted probability of patients receiving a 5-day antibiotic therapy increased to 45.9% (P < .001) over the study period, with the odds of this duration increasing (adjusted odds ratio [aOR] 1.10; 95% CI 1.07-1.14) and composite adverse events decreasing (aOR 0.98; 95% CI 0.96-0.99) with each successive quarter.

Study details: This study included 6,553 patients eligible for a 5-day therapy for uncomplicated CAP who were admitted to any of the 41 hospitals that participated in a state-wide collaborative quality initiative, Michigan Hospital Medicine Safety Consortium, for the entire 3-year study period.

Disclosures: The study was sponsored by Blue Cross Blue Shield of Michigan and a career development award from the Agency for Healthcare Research and Quality to the lead author who, along with other authors, also declared receiving salary, research grants, or speaker honoraria from additional sources.

Source: Vaughn VM et al. Clin Infect Dis. 2021:ciab950 (Nov 13). Doi: 10.1093/cid/ciab950.

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Key clinical point: Reinforcement of antibiotic stewardship by forming large multihospital collaboratives increases adherence to the appropriate 5-day therapy for uncomplicated community-acquired pneumonia (CAP) while decreasing adverse events.

Main finding: After adjusting for hospital clustering, the 20.9% predicted probability of patients receiving a 5-day antibiotic therapy increased to 45.9% (P < .001) over the study period, with the odds of this duration increasing (adjusted odds ratio [aOR] 1.10; 95% CI 1.07-1.14) and composite adverse events decreasing (aOR 0.98; 95% CI 0.96-0.99) with each successive quarter.

Study details: This study included 6,553 patients eligible for a 5-day therapy for uncomplicated CAP who were admitted to any of the 41 hospitals that participated in a state-wide collaborative quality initiative, Michigan Hospital Medicine Safety Consortium, for the entire 3-year study period.

Disclosures: The study was sponsored by Blue Cross Blue Shield of Michigan and a career development award from the Agency for Healthcare Research and Quality to the lead author who, along with other authors, also declared receiving salary, research grants, or speaker honoraria from additional sources.

Source: Vaughn VM et al. Clin Infect Dis. 2021:ciab950 (Nov 13). Doi: 10.1093/cid/ciab950.

Key clinical point: Reinforcement of antibiotic stewardship by forming large multihospital collaboratives increases adherence to the appropriate 5-day therapy for uncomplicated community-acquired pneumonia (CAP) while decreasing adverse events.

Main finding: After adjusting for hospital clustering, the 20.9% predicted probability of patients receiving a 5-day antibiotic therapy increased to 45.9% (P < .001) over the study period, with the odds of this duration increasing (adjusted odds ratio [aOR] 1.10; 95% CI 1.07-1.14) and composite adverse events decreasing (aOR 0.98; 95% CI 0.96-0.99) with each successive quarter.

Study details: This study included 6,553 patients eligible for a 5-day therapy for uncomplicated CAP who were admitted to any of the 41 hospitals that participated in a state-wide collaborative quality initiative, Michigan Hospital Medicine Safety Consortium, for the entire 3-year study period.

Disclosures: The study was sponsored by Blue Cross Blue Shield of Michigan and a career development award from the Agency for Healthcare Research and Quality to the lead author who, along with other authors, also declared receiving salary, research grants, or speaker honoraria from additional sources.

Source: Vaughn VM et al. Clin Infect Dis. 2021:ciab950 (Nov 13). Doi: 10.1093/cid/ciab950.

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T2DM deteriorates clinical outcomes of severe community-acquired pneumonia

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Key clinical point: Patients with severe community-acquired pneumonia (SCAP) who also have type 2 diabetes mellitus (T2DM) have poorer clinical outcomes than those without T2DM.

Main finding: Compared with patients with SCAP but without T2DM, those with both exhibited higher rates of hospital mortality (35.2% vs. 31.0%; P = .009), 14-day mortality (15.0% vs. 10.8%; P < .001), 30-day mortality (25.7% vs. 22.7%; P = .046), and intensive care unit (ICU) mortality (30.8% vs. 26.5%; P = .005) along with a longer ICU length of stay (13 days vs. 12 days; P = .016).

Study details: Findings are from a retrospective, single-center, observational study including 3,786 adult patients admitted to an ICU for SCAP, among whom 1,262 patients with T2DM were matched to 2,524 patients without T2DM.

Disclosures: The study received funding from the National Natural Science Foundation of China, Science and Technology Department of Sichuan Province, and National Key Research and Development Program of China. The authors declared having no conflict of interests.

Source: Huang D et al. Crit Care. 2021;25:419 (Dec 7). Doi: 10.1186/s13054-021-03841-w.

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Key clinical point: Patients with severe community-acquired pneumonia (SCAP) who also have type 2 diabetes mellitus (T2DM) have poorer clinical outcomes than those without T2DM.

Main finding: Compared with patients with SCAP but without T2DM, those with both exhibited higher rates of hospital mortality (35.2% vs. 31.0%; P = .009), 14-day mortality (15.0% vs. 10.8%; P < .001), 30-day mortality (25.7% vs. 22.7%; P = .046), and intensive care unit (ICU) mortality (30.8% vs. 26.5%; P = .005) along with a longer ICU length of stay (13 days vs. 12 days; P = .016).

Study details: Findings are from a retrospective, single-center, observational study including 3,786 adult patients admitted to an ICU for SCAP, among whom 1,262 patients with T2DM were matched to 2,524 patients without T2DM.

Disclosures: The study received funding from the National Natural Science Foundation of China, Science and Technology Department of Sichuan Province, and National Key Research and Development Program of China. The authors declared having no conflict of interests.

Source: Huang D et al. Crit Care. 2021;25:419 (Dec 7). Doi: 10.1186/s13054-021-03841-w.

Key clinical point: Patients with severe community-acquired pneumonia (SCAP) who also have type 2 diabetes mellitus (T2DM) have poorer clinical outcomes than those without T2DM.

Main finding: Compared with patients with SCAP but without T2DM, those with both exhibited higher rates of hospital mortality (35.2% vs. 31.0%; P = .009), 14-day mortality (15.0% vs. 10.8%; P < .001), 30-day mortality (25.7% vs. 22.7%; P = .046), and intensive care unit (ICU) mortality (30.8% vs. 26.5%; P = .005) along with a longer ICU length of stay (13 days vs. 12 days; P = .016).

Study details: Findings are from a retrospective, single-center, observational study including 3,786 adult patients admitted to an ICU for SCAP, among whom 1,262 patients with T2DM were matched to 2,524 patients without T2DM.

Disclosures: The study received funding from the National Natural Science Foundation of China, Science and Technology Department of Sichuan Province, and National Key Research and Development Program of China. The authors declared having no conflict of interests.

Source: Huang D et al. Crit Care. 2021;25:419 (Dec 7). Doi: 10.1186/s13054-021-03841-w.

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Cefoperazone-sulbactam: A potential therapeutic alternative to piperacillin-tazobactam in severe community-acquired pneumonia

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Key clinical point: Owing to a similar clinical efficacy and safety profile to piperacillin-tazobactam (PIP-TAZ), cefoperazone-sulbactam (CFP-SUL) could be used as an alternative for treating severe community-acquired pneumonia (SCAP) in elderly patients.

Main finding: The odds for clinical cure (adjusted odds ratio [aOR] 1.10; 95% CI 0.71-1.70), clinical effectiveness (aOR 0.99; 95% CI 0.62-1.59), all-cause mortality (aOR 0.95; 95% CI 0.60-1.48), and pneumonia-related mortality (aOR 0.88; 95% CI 0.51-1.53) were similar between patients with SCAP receiving CFP-SUL and those receiving PIP-TAZ. Both drug combinations were equally well tolerated.

Study details: Based on the retrospective multicenter registry BATTLE, the study included 624 patients with SCAP among 317 others with hospital- or ventilator-acquired pneumonia who were aged 65 years when diagnosed with pneumonia.

Disclosures: The authors disclosed receiving no financial support for the study. None of the authors declared any conflict of interests.

Source: Huang CT et al. Int J Antimicrob Agents. 2021;106491 (Dec 4). Doi: 10.1016/j.ijantimicag.2021.106491.

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Key clinical point: Owing to a similar clinical efficacy and safety profile to piperacillin-tazobactam (PIP-TAZ), cefoperazone-sulbactam (CFP-SUL) could be used as an alternative for treating severe community-acquired pneumonia (SCAP) in elderly patients.

Main finding: The odds for clinical cure (adjusted odds ratio [aOR] 1.10; 95% CI 0.71-1.70), clinical effectiveness (aOR 0.99; 95% CI 0.62-1.59), all-cause mortality (aOR 0.95; 95% CI 0.60-1.48), and pneumonia-related mortality (aOR 0.88; 95% CI 0.51-1.53) were similar between patients with SCAP receiving CFP-SUL and those receiving PIP-TAZ. Both drug combinations were equally well tolerated.

Study details: Based on the retrospective multicenter registry BATTLE, the study included 624 patients with SCAP among 317 others with hospital- or ventilator-acquired pneumonia who were aged 65 years when diagnosed with pneumonia.

Disclosures: The authors disclosed receiving no financial support for the study. None of the authors declared any conflict of interests.

Source: Huang CT et al. Int J Antimicrob Agents. 2021;106491 (Dec 4). Doi: 10.1016/j.ijantimicag.2021.106491.

Key clinical point: Owing to a similar clinical efficacy and safety profile to piperacillin-tazobactam (PIP-TAZ), cefoperazone-sulbactam (CFP-SUL) could be used as an alternative for treating severe community-acquired pneumonia (SCAP) in elderly patients.

Main finding: The odds for clinical cure (adjusted odds ratio [aOR] 1.10; 95% CI 0.71-1.70), clinical effectiveness (aOR 0.99; 95% CI 0.62-1.59), all-cause mortality (aOR 0.95; 95% CI 0.60-1.48), and pneumonia-related mortality (aOR 0.88; 95% CI 0.51-1.53) were similar between patients with SCAP receiving CFP-SUL and those receiving PIP-TAZ. Both drug combinations were equally well tolerated.

Study details: Based on the retrospective multicenter registry BATTLE, the study included 624 patients with SCAP among 317 others with hospital- or ventilator-acquired pneumonia who were aged 65 years when diagnosed with pneumonia.

Disclosures: The authors disclosed receiving no financial support for the study. None of the authors declared any conflict of interests.

Source: Huang CT et al. Int J Antimicrob Agents. 2021;106491 (Dec 4). Doi: 10.1016/j.ijantimicag.2021.106491.

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