Macrolide Combination Therapy Research Articles

Acute management of pneumonia in adult patients.

Acute management of pneumonia in adult patients.

Beta-Lactam Plus Macrolide for Patients Hospitalized With Community-Acquired Pneumonia: Difference Between Autumn and Spring.

The 2017 Korean guideline on community-acquired pneumonia (CAP) recommended beta-lactam plus macrolide combination therapy for patients hospitalized with severe pneumonia, and beta-lactam monotherapy for mild-to-moderate pneumonia. However, antibiotic treatment regimen for mild-to-moderate CAP has never been evaluated for Korean patients. In this retrospective cohort study, study patients were selected from three evaluation periods (October 1 to December 31, 2014; April 1 to June 30, 2016; October 1 to December 31, 2017) of the National Quality Assessment Program for CAP management and the National Health Insurance data on the selected patients was extracted from 1 year before the first patient enrollment and 1 year after the last patient enrollment at each evaluation period for the analysis of risk adjustment and outcomes. The survival rates between beta-lactam plus macrolide (BM) groups and beta-lactam monotherapy (B) were compared using a Kaplan-Meier survival analysis after propensity score matching by age, gender, confusion, urea, respiratory rate, blood pressure at age of 65 years or older (CURB-65), and Charlson comorbidity index for risk adjustment. The differences between autumn and spring season were also evaluated. A total of 30,053 patients were enrolled. Mean age and the male-to-female ratio were 64.7 ± 18.4 and 14,197:15,856, respectively. After matching, 2,397 patients in each group were analyzed. The 30-day survival rates did not differ between the BM and B groups (97.3% vs. 96.5%, P = 0.081). In patients with CURB-65 ≥ 2, the 30-day survival rate was higher in the BM than in the B group (93.7% vs. 91.0%, P = 0.044). Among patients with CURB-65 ≥ 2, the 30-day survival rate was higher in the BM than in the B group (93.3% vs. 88.5%, P = 0.009) during autumn season, which was not observed during spring (94.2% vs. 94.1%, P = 0.986). Beta-lactam plus macrolide combination therapy shows potential as an empirical therapy for CAP with CURB-65 ≥ 2, especially in autumn.

Respiratory Fluoroquinolone Monotherapy Versus Β-Lactam Plus Macrolide Combination Therapy for Hospitalised Adults with Community-Acquired Pneumonia: A Systematic Review and Meta-Analysis of Randomised Controlled Trials

Respiratory Fluoroquinolone Monotherapy Versus Β-Lactam Plus Macrolide Combination Therapy for Hospitalised Adults with Community-Acquired Pneumonia: A Systematic Review and Meta-Analysis of Randomised Controlled Trials

Usefulness of β-lactam and macrolide combination therapy for treating community-acquired pneumonia patients hospitalized in the intensive care unit: Propensity score analysis of a prospective cohort study

IntroductionWhether β-lactam and macrolide combination therapy reduces mortality in severe community-acquired pneumonia (SCAP) patients hospitalized in the intensive care unit (ICU) is controversial. The aim of the present study was to evaluate the usefulness of β-lactam and macrolide combination therapy for SCAP patients hospitalized in the ICU. MethodsA prospective, observational, cohort study of hospitalized pneumonia patients was performed. Hospitalized SCAP patients admitted to the ICU within 24 h between October 2010 and October 2017 were included for analysis. The primary outcome was 30-day mortality, and secondary outcomes were 14-day mortality and ICU mortality. Inverse probability of treatment weighting (IPTW) analysis as a propensity score analysis was used to reduce biases, including six covariates: age, sex, C-reactive protein, albumin, Pneumonia Severity Index score, and APACHE II score. ResultsA total of 78 patients were included, with 48 patients in the non-macrolide-containing β-lactam therapy group and 30 patients in the macrolide combination therapy group. β-lactam and macrolide combination therapy significantly decreased 30-day mortality (16.7% vs. 43.8%; P = 0.015) and 14-day mortality (6.7% vs. 31.3%; P = 0.020), but not ICU mortality (10% vs 27.1%, P = 0.08) compared with non-macrolide-containing β-lactam therapy. After adjusting by IPTW, macrolide combination therapy also decreased 30-day mortality (odds ratio, 0.29; 95%CI, 0.09–0.96; P = 0.04) and 14-day mortality (odds ratio, 0.19; 95%CI, 0.04–0.92; P = 0.04), but not ICU mortality (odds ratio, 0.34; 95%CI, 0.08–1.36; P = 0.13). ConclusionsCombination therapy with β-lactam and macrolides significantly improved the prognosis of SCAP patients hospitalized in the ICU compared with a non-macrolide-containing β-lactam regimen.

Comparative Efficacy of Beta-Lactams and Macrolides in the Treatment of Pediatric Pneumonia: A Systematic Review.

Pneumonia is an acute infection of the lung parenchyma that is differentiated among three main diagnoses: community-acquired pneumonia (CAP), hospital-acquired pneumonia (HAP), and healthcare-associated pneumonia (HCAP). Though CAP is initially presented as a mild infection, it contributes to childhood mortality rates globally. A vast number of pathogens are the cause of CAP, but the two main causative organisms include Streptococcus pneumoniae and Haemophilus influenzae, with the former causing up to 50% of all childhood cases. In the current treatment guidelines from the Infectious Diseases Society of America (IDSA), amoxicillin is the recommended treatment choice for mild-to-moderate CAP while ampicillin is recommended for cases of severe CAP. Previous studies compared treatment between macrolides and beta-lactams to provide more information on the effectiveness in the pediatric population. The objective of this article is to systematically review the literature on the comparative efficacy of beta-lactams and macrolides in the treatment of community-acquired pneumonia among children and to evaluate the outcomes that are used to determine drug efficacy in order to provide medication recommendations. A systematic literature search was conducted in PubMed, TRIP, Cochrane and SCOPUS. Cohort studies and randomized controlled trials between the years 2000 and 2020 that compared the efficacy of amoxicillin and macrolides in treating pediatric pneumonia were included in the systematic review. Eligible patients included patients who were 17 years and younger, diagnosed with community-acquired pneumonia, and were given beta-lactams or macrolides, either as monotherapy or combination. Two reviewers were involved in the appraisal process to assess the quality of the methods used in the selected studies. A total of six articles were eligible according to the inclusion criteria and quality assessment. Four articles compared beta-lactam monotherapy with beta-lactam and macrolide combination therapy, while Kogan R et al. compared macrolide therapy monotherapy with beta-lactam and macrolide combination therapy and Leyenaar JK et al. compared ceftriaxone monotherapy to ceftriaxone plus macrolide combination therapy. The studies defined treatment failure as either a change in antibiotic therapy or hospital admission within 14 days of CAP diagnosis. Three studies used the length of hospital stay as their primary outcome for comparison of treatment efficacy. Four studies showed that the use of macrolides provided better treatment outcomes by reducing hospital stay and treatment failure rates. Beta-lactam and macrolide combination therapy did not show a significant effect on treatment failure compared to beta-lactam monotherapy regimens and it did not affect mortality compared to placebo or diet alone. Within the macrolide class, azithromycin was more clinically significant compared to erythromycin. The use of macrolides as monotherapy or add-on therapy to beta-lactams is more effective in the treatment of community-acquired pneumonia in the pediatric population.

Effect of β-Lactam Plus Macrolide Versus Fluoroquinolone on 30-Day Readmissions for Community-Acquired Pneumonia.

Antibiotic therapy with a macrolide and β-lactam or a fluoroquinolone for the empirical treatment of community-acquired pneumonia (CAP) in an inpatient non-intensive care setting is recommended per guidelines. Studies show that these treatments have similar outcomes, including death, adverse effects, and bacterial eradication. However, a comparison of 30-day readmission rates between these treatments is limited. To determine whether 30-day readmissions for patients treated for CAP in a regional hospital differed between a fluoroquinolone monotherapy and a β-lactam plus macrolide combination therapy. Retrospective cohort study of patients aged ≥18 years with a CAP diagnosis who were admitted to the same regional hospital from December 1, 2011, through December 1, 2016. Patients receiving a third-generation cephalosporin plus macrolide were compared with those receiving a respiratory fluoroquinolone. Exclusion criteria were concurrent or recent use of the study antibiotics; death, transfer, or transition to hospice; and diagnosis of hospital-acquired pneumonia or health care-associated pneumonia. The collected data were 30-day readmission rates, antibiotic regimens, demographic characteristics, and pneumonia severity index and comorbidity scores. Association between treatment group and readmissions was assessed with logistic regression. Association between readmissions and individual data points between the 2 treatment groups was calculated with multivariate regression and odds ratio (95% confidence interval). Of 432 patients, 171 met inclusion criteria (fluoroquinolone group, n = 101; β-lactam plus macrolide group, n = 70). Thirty-day readmissions were not significantly different between the fluoroquinolone group and β-lactam plus macrolide group (P = 0.58). Increased 30-day readmissions were independently associated with male sex and hospital length of stay (P < 0.05). Length of stay was approximately 3 days and did not differ between treatment groups. No difference was seen in 30-day readmissions between CAP patients who received fluoroquinolone monotherapy and those who received β-lactam plus macrolide combination therapy.

Azithromycin combination therapy for community-acquired pneumonia: propensity score analysis

Whether macrolide combination therapy reduces the mortality of patients with severe community-acquired pneumonia (CAP) hospitalized in the non-intensive care unit (ICU) remains unclear. Therefore, we investigated the efficacy of adding azithromycin to β-lactam antibiotics for such patients. This prospective cohort study enrolled consecutive patients with CAP hospitalized in the non-ICU between October 2010 and November 2016. The 30-day mortality between β-lactam and azithromycin combination therapy and β-lactam monotherapy was compared in patients classified as mild to moderate and severe according to the CURB-65, Pneumonia Severity Index (PSI), and Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) criteria. Inverse probability of treatment weighting (IPTW) analysis was used to reduce biases. Based on the CURB-65 and PSI, combination therapy did not significantly reduce the 30-day mortality in either group (179 patients in the combination group, 952 in the monotherapy group). However, based on the IDSA/ATS criteria, combination therapy significantly reduced the 30-day mortality in patients with severe (odds ratio [OR] 0.12, 95% confidence interval [CI] 0.007–0.57), but not non-severe pneumonia (OR 1.85, 95% CI 0.51–5.40); these results were similar after IPTW analysis. Azithromycin combination therapy significantly reduced the mortality of patients with severe CAP who met the IDSA/ATS criteria.

Outcomes of Macrolide Deescalation in Severe Community-acquired Pneumonia

PurposeCurrent data suggest potential benefits with β-lactam plus macrolide combination therapy for empiric treatment of intensive care unit (ICU) patients with severe community-acquired pneumonia (CAP). However, it is unclear whether deescalation to β-lactam monotherapy in the absence of positive results on diagnostic tests, such as the BioFire FilmArray Respiratory Panel 2 (BioFire polymerase chain reaction [PCR]), affects clinical outcomes. The purpose of this study was to compare outcomes between patients with negative BioFire PCR results deescalated to β-lactam monotherapy with those not deescalated. MethodsThis single-center, retrospective cohort study assessed the in-hospital mortality rates of critically ill adults with CAP treated for ≥48 h with combination β-lactam and azithromycin therapy. Additional end points included hospital length of stay (LOS), ICU LOS, duration of mechanical ventilatory support, 30-day readmission, and incidence of azithromycin-related adverse effects. FindingsA total of 94 patients were included: 53 in the deescalation group and 41 in the nondeescalation group. No difference was observed with respect to in-hospital mortality (2.4% vs 11.3%, P = 0.312), although patients in the deescalated group experienced shorter ICU (1.9 vs 3.4 days, P = 0.029) and hospital LOS (6 vs 7 days, P = 0.025). No differences were found between groups with respect to additional secondary end points. Simple logistic regression confirmed that deescalation was not associated with hospital mortality (odds ratio = 0.17, 95% CI, 0.02–1.70). ImplicationsIn this study of ICU patients with severe CAP and a negative BioFire PCR result, deescalation from combination β-lactam and macrolide therapy to β-lactam monotherapy was not associated with increased in-hospital mortality but was associated with decreased hospital and ICU LOS. Larger prospective studies are warranted to verify these findings.

Macrolide combination therapy for patients hospitalised with community-acquired pneumonia? An individualised approach supported by machine learning

The role of macrolide/β-lactam combination therapy in community-acquired pneumonia (CAP) of moderate severity is a matter of debate. Macrolides expand the coverage to atypical pathogens and attenuate pulmonary inflammation, but have been associated with cardiovascular toxicity and drug interactions. We developed a decision tree based on aetiological and clinical parameters, which are available ex ante to support a personalised decision for or against macrolides for the best clinical outcome of the individual patient. We employed machine learning in a cross-validation scheme based on a well-balanced selection of 4898 patients after propensity score matching to data available on admission of 6440 hospitalised patients with moderate severity (non-intensive care unit patients) from the observational, prospective, multinational CAPNETZ study. We aimed to improve the primary outcome of 180-day survival. We found a simple decision tree of patient characteristics comprising chronic cardiovascular and chronic respiratory comorbidities as well as leukocyte counts in the respiratory secretion at enrolment. Specifically, we found that patients without cardiovascular or patients with respiratory comorbidities and high leukocyte counts in the respiratory secretion benefit from macrolide treatment. Patients identified to be treated in compliance with our treatment suggestion had a lower mortality of 27% (OR 1.83, 95% CI 1.48-2.27; p<0.001) compared to the observed standard of care. Stratifying macrolide treatment in patients following a simple treatment rule may lead to considerably reduced mortality in CAP. A future randomised controlled trial confirming our result is necessary before implementing this rule into the clinical routine.

Moving Past the Routine Use of Macrolides-Reviewing the Role of Combination Therapy in Community-Acquired Pneumonia.

Purpose of ReviewDespite advances in diagnostic microbiology and sepsis management, community-acquired pneumonia (CAP) remains a significant cause of morbidity and mortality. Current recommendations regarding the use of beta-lactams in combination with macrolides published in clinical practice guidelines are variable and based on low-quality evidence that is frequently retrospective, observational, and heterogeneous in nature. While population-based studies have historically suggested improved clinical outcomes with the routine use of macrolide combination therapy in hospitalized patients with CAP, emerging evidence from recent randomized controlled trials has challenged this practice. In this article, we discuss the historical rationale and current evidence for combination macrolide therapy in the management of CAP.Recent FindingsRecent randomized controlled trials have assessed the non-inferiority of beta-lactam monotherapy compared to beta-lactam/macrolide combination therapy in adult patients hospitalized with CAP. Beta-lactam monotherapy was associated with equivalent clinical outcomes in patients with mild to moderate CAP. Patients with severe CAP managed with beta-lactam monotherapy have demonstrated worse clinical outcomes when compared to patients treated with combination therapy. In addition, previous beta-lactam exposure prior to hospitalization has not been shown to negatively impact outcomes in patients managed with beta-lactam monotherapy in the hospital.SummaryCurrent evidence supports the use of beta-lactam monotherapy in adult patients hospitalized with mild to moderate CAP. While existing evidence supports the use of combination therapy in patients with severe pneumonia, further large-scale randomized controlled trials are urgently needed to clarify the role of combination therapy in this population.

Use of macrolide and beta-lactam combination therapy in paediatric community-acquired pneumonia

Use of macrolide and beta-lactam combination therapy in paediatric community-acquired pneumonia

Inpatient management of community-acquired pneumonia at the European Gaza Hospital: a clinical audit

BackgroundDisease severity scores such as CURB-65 are often used to guide the management of patients with community-acquired pneumonia. Early and adequate empirical antibiotic treatment reduces mortality. The aim of this study was to examine the severity assessment and management of patients presenting with community-acquired pneumonia at the European Gaza Hospital in the Gaza Strip and to compare this to the best available evidence. MethodsMedical records of all patients admitted to the European Gaza Hospital with a diagnosis of community-acquired pneumonia between Dec 1, 2015, and March 31, 2016, were reviewed retrospectively. Clinical practice was compared with recommendations for severity assessment and the management of community-acquired pneumonia, as reported in guidelines by the National Institute for Health and Care Excellence and the American Thoracic Society. Ethical approval was obtained from the General Directorate of Human Resources. Findings141 patients were admitted to the European Gaza Hospital with community-acquired pneumonia during the study period. Records of 41 patients were missing or could not be retrieved. The mean age of patients was 55·9 years (SD 20·2). Blood urea and nitrogen concentrations were not documented for 48 (48%) patients, and respiratory rate was not documented for 73 (73%) patients. The CURB-65 score was determined only for 12 (12%) patients. Microbiological testing was done only for two (2%) patients. Although 18 different antibiotic regimens were used, 81 (81%) patients received a β-lactam plus macrolide combination therapy, either given alone (49 [49%] patients) or with another antibiotic (32 [32%] patients), which is in line with the recommendations for patients admitted to hospital with community-acquired pneumonia. 43 (43%) patients received anti-viral drugs, and 41 (41%) patients received corticosteroids. InterpretationClinicians were poorly adherent to current standards of care in severity assessment and management of community-acquired pneumonia. Moreover, the broad range of antibiotic regimes used, without microbiological guidance, was inappropriate and will have increased the risk of antibiotic resistance. A local evidence-based clinical practice guideline should be developed and implemented. Furthermore, the documentation system should be improved to enhance the continuity of care and clinical auditing. FundingNone.

Mortality in patients with community-onset pneumonia at low risk of drug-resistant pathogens: Impact of β-lactam plus macrolide combination therapy.

Drug-resistant pathogen (DRP) risk stratification is important for choosing a treatment strategy for community-onset pneumonia. Evidence for benefits of non-antipseudomonal β-lactam plus macrolide combination therapy (BLM) on mortality is limited in patients at low DRP risk. Risk factors for mortality remain to be clarified. Post hoc analysis using a prospective multicentre study cohort of community-onset pneumonia was performed to assess 30-day differences in mortality between non-antipseudomonal β-lactam monotherapy (BL) and BLM groups. Logistic regression analysis was performed to assess the therapeutic effect and risk factors for mortality in patients at low DRP risk. In total, 594 patients with community-onset pneumonia at low DRP risk (369 BL and 225 BLM) were analysed. The 30-day mortality in BL and BLM was 13.8% and 1.8%, respectively (P < 0.001). Multivariate analysis showed that BLM reduced the 30-day mortality (adjusted odds ratio: 0.28, 95% CI: 0.09-0.87) compared with BL. Independent prognostic factors for 30-day mortality included arterial partial pressure of carbon dioxide (PaCO2 ) > 50 mm Hg, white blood cell count < 4000/mm3 , non-ambulatory status, albumin < 3.0 g/dL, haematocrit < 30%, age ≥ 80 years, respiratory rate > 25/min and body temperature < 36°C. In patients with community-onset pneumonia at low DRP risk, BLM treatment reduced 30-day mortality compared with BL. Independent risk factors for mortality are potential confounding factors when assessing antibiotic effects in randomized clinical trials.

IMPLICATION OF β‐LACTAM PLUS MACROLIDE COMBINATION THERAPY ON MORTALITY IN PATIENTS WITH COMMUNITY‐ONSET PNEUMONIA AT LOW RISK FOR DRUG‐RESISTANT PATHOGENS

RespirologyVolume 22, Issue S3 p. 271-271 APSR Poster Abstracts IMPLICATION OF β-LACTAM PLUS MACROLIDE COMBINATION THERAPY ON MORTALITY IN PATIENTS WITH COMMUNITY-ONSET PNEUMONIA AT LOW RISK FOR DRUG-RESISTANT PATHOGENS First published: 23 November 2017 https://doi.org/10.1111/resp.13207_498Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume22, IssueS3Supplement: 22nd Congress of the Asian Pacific Society of Respirology, International Convention Centre, Sydney, Australia, 23–26 November 2017November 2017Pages 271-271 RelatedInformation

Effectiveness of β-Lactam Monotherapy vs Macrolide Combination Therapy for Children Hospitalized With Pneumonia

β-Lactam monotherapy and β-lactam plus macrolide combination therapy are both common empirical treatment strategies for children hospitalized with pneumonia, but few studies have evaluated the effectiveness of these 2 treatment approaches. To compare the effectiveness of β-lactam monotherapy vs β-lactam plus macrolide combination therapy among a cohort of children hospitalized with pneumonia. We analyzed data from the Etiology of Pneumonia in the Community Study, a multicenter, prospective, population-based study of community-acquired pneumonia hospitalizations conducted from January 1, 2010, to June 30, 2012, in 3 children's hospitals in Nashville, Tennessee; Memphis, Tennessee; and Salt Lake City, Utah. The study included all children (up to 18 years of age) who were hospitalized with radiographically confirmed pneumonia and who received β-lactam monotherapy or β-lactam plus macrolide combination therapy. Data analysis was completed in April 2017. We defined the referent as β-lactam monotherapy, including exclusive use of an oral or parenteral second- or third-generation cephalosporin, penicillin, ampicillin, ampicillin-sulbactam, amoxicillin, or amoxicillin-clavulanate. Use of a β-lactam plus an oral or parenteral macrolide (azithromycin or clarithromycin) served as the comparison group. We modeled the association between these groups and patients' length of stay using multivariable Cox proportional hazards regression. Covariates included demographic, clinical, and radiographic variables. We further evaluated length of stay in a cohort matched by propensity to receive combination therapy. Logistic regression was used to evaluate secondary outcomes in the unmatched cohort, including intensive care admission, rehospitalizations, and self-reported recovery at follow-up. Our study included 1418 children (693 girls and 725 boys) with a median age of 27 months (interquartile range, 12-69 months). This cohort was 60.1% of the 2358 children enrolled in the Etiology of Pneumonia in the Community Study with radiographically confirmed pneumonia in the study period; 1019 (71.9%) received β-lactam monotherapy and 399 (28.1%) received β-lactam plus macrolide combination therapy. In the unmatched cohort, there was no statistically significant difference in length of hospital stay between children receiving β-lactam monotherapy and combination therapy (median, 55 vs 59 hours; adjusted hazard ratio, 0.87; 95% CI, 0.74-1.01). The propensity-matched cohort (n = 560, 39.5%) showed similar results. There were also no significant differences between treatment groups for the secondary outcomes. Empirical macrolide combination therapy conferred no benefit over β-lactam monotherapy for children hospitalized with community-acquired pneumonia. The results of this study elicit questions about the routine empirical use of macrolide combination therapy in this population.

Advances in the prevention, management, and treatment of community-acquired pneumonia.

Community-acquired pneumonia (CAP) is the infectious disease with the highest number of deaths worldwide. Nevertheless, its importance is often underestimated. Large cohorts of patients with CAP have been established worldwide and improved our knowledge about CAP by far. Therefore, current guidelines are much more evidence-based than ever before. This article discusses recent major studies and concepts on CAP such as the role of biomarkers, appropriate risk stratification to identify patients in need of hospitalisation or intensive care, appropriate empiric antibiotic therapy (including the impact of macrolide combination therapy and antibiotic stewardship), and CAP prevention with novel influenza and pneumococcal vaccines.

Antibiotic Treatment Strategies for Community-Acquired Pneumonia in Adults

BackgroundThe choice of empirical antibiotic treatment for patients with clinically suspected community-acquired pneumonia (CAP) who are admitted to non–intensive care unit (ICU) hospital wards is complicated by the limited availability of evidence. We compared strategies of empirical treatment (allowing deviations for medical reasons) with beta-lactam monotherapy, beta-lactam–macrolide combination therapy, or fluoroquinolone monotherapy.MethodsIn a cluster-randomized, crossover trial with strategies rotated in 4-month periods, we tested the noninferiority of the beta-lactam strategy to the beta-lactam–macrolide and fluoroquinolone strategies with respect to 90-day mortality, in an intention-to-treat analysis, using a noninferiority margin of 3 percentage points and a two-sided 90% confidence interval.ResultsA total of 656 patients were included during the beta-lactam strategy periods, 739 during the beta-lactam–macrolide strategy periods, and 888 during the fluoroquinolone strategy periods, with rates of adherence to the strategy of 93.0%, 88.0%, and 92.7%, respectively. The median age of the patients was 70 years. The crude 90-day mortality was 9.0% (59 patients), 11.1% (82 patients), and 8.8% (78 patients), respectively, during these strategy periods. In the intention-to-treat analysis, the risk of death was higher by 1.9 percentage points (90% confidence interval [CI], −0.6 to 4.4) with the beta-lactam–macrolide strategy than with the beta-lactam strategy and lower by 0.6 percentage points (90% CI, −2.8 to 1.9) with the fluoroquinolone strategy than with the beta-lactam strategy. These results indicated noninferiority of the beta-lactam strategy. The median length of hospital stay was 6 days for all strategies, and the median time to starting oral treatment was 3 days (interquartile range, 0 to 4) with the fluoroquinolone strategy and 4 days (interquartile range, 3 to 5) with the other strategies.ConclusionsAmong patients with clinically suspected CAP admitted to non-ICU wards, a strategy of preferred empirical treatment with beta-lactam monotherapy was noninferior to strategies with a beta-lactam–macrolide combination or fluoroquinolone monotherapy with regard to 90-day mortality. (Funded by the Netherlands Organization for Health Research and Development; CAP-START ClinicalTrials.gov number, NCT01660204.)

Comparative Effectiveness of Empiric β-Lactam Monotherapy and β-Lactam–Macrolide Combination Therapy in Children Hospitalized with Community-Acquired Pneumonia

To determine the comparative effectiveness of β-lactam monotherapy and β-lactam and macrolide combination therapy on clinical outcomes in the treatment of children hospitalized with community-acquired pneumonia (CAP). This multicenter retrospective cohort study included children aged 1-18 years who were hospitalized with CAP and received β-lactam antibiotic therapy either alone or in combination with a macrolide. Data were obtained from the Pediatric Health Information System. Associations between empiric antibiotic therapy and hospital readmission for the same episode of pneumonia were estimated using exact logistic regression. Associations between empiric antibiotic therapy and length of hospital stay were estimated using a generalized estimating equation with negative binomial distribution. There were 20 743 patients hospitalized with CAP. Of these, 24% received β-lactam and macrolide combination therapy on admission. Compared with children who received β-lactam monotherapy, children who received β-lactam plus macrolide combination therapy were 20% less likely to stay in the hospital an additional day (adjusted relative risk 0.80; 95% CI, 0.75-0.86) but did not have a different readmission rate (relative risk 0.69; 95% CI, 0.41-1.12). An effect of combination treatment on reduced length of stay was not evident in children <6 years of age but increased with increasing age groups thereafter. School-aged patients hospitalized with CAP who received β-lactam plus macrolide combination therapy have a shorter length of stay and similar rates of readmission compared with school-aged patients who receive β-lactam monotherapy.

Fluoroquinolone–macrolide combination therapy for chronic bacterial prostatitis: retrospective analysis of pathogen eradication rates, inflammatory findings and sexual dysfunction

We previously demonstrated the safety and efficacy of fluoroquinolone-macrolide combination therapy in category II chronic bacterial prostatitis (CBP). The aim of this study is to retrospectively compare the microbiological and clinical findings of two treatment schemes for CBP based on the combination of azithromycin (500 mg, thrice-weekly) with a once-daily 500- or 750-mg dose of ciprofloxacin (Cipro-500 or Cipro-750 cohort, respectively). Combined administration of azithromycin (1500 mg week(-1)) with ciprofloxacin at the rate of 750 mg day(-1) for 4 weeks rather than at 500 mg day(-1) for 6 weeks increased the eradication rates from 62.35% to 77.32% and the total bacteriological success from 71.76% to 85.57%. A significant decrease in pain and voiding signs/symptoms and a significant reduction in inflammatory leukocyte counts and serum prostate-specific antigen (PSA) were sustained throughout an 18-month follow-up period in both groups. Ejaculatory pain, haemospermia and premature ejaculation were significantly attenuated on microbiological eradication in both groups, but the latter subsided more promptly in the Cipro-750 cohort. In total, 59 Cipro-750 patients showed mild-to-severe erectile dysfunction (ED) at baseline, while 22 patients had no ED on microbiological eradication and throughout the follow-up period. In conclusion fluoroquinolone-macrolide therapy resulted in pathogen eradication and CBP symptom attenuation, including pain, voiding disturbances and sexual dysfunction. A once-daily 750-mg dose of ciprofloxacin for 4 weeks showed enhanced eradication rates and lower inflammatory white blood cell counts compared to the 500-mg dose for 6 weeks. Our results are open to further prospective validation.

Fluoroquinolones in Community-Acquired Pneumonia

Fluoroquinolone use has dramatically increased since the introduction of the first respiratory fluoroquinolone in the late 1990s. Over a relatively brief period of time, the respiratory fluoroquinolones have supplanted other first-line options as the predominant community-acquired pneumonia (CAP) therapy in hospitals. This article discusses the rise of the fluoroquinolone era, debates the comparative effectiveness of fluoroquinolones for CAP therapy, examines fluoroquinolone resistance and adverse drug reactions, and discusses new trends in pneumonia epidemiology and outcomes assessment. Overall, published data suggest that fluoroquinolone monotherapy is associated with improved patient survival compared with β-lactam monotherapy and similar survival to β-lactam plus macrolide combination therapy. Fluoroquinolone monotherapy may be associated with shorter hospital length of stay compared with β-lactam plus macrolide combination therapy, particularly in severe pneumonia or with high-dose therapy. There is insufficient evidence to conclude that any individual fluoroquinolone therapy is better than another with regards to patient mortality. Fluoroquinolones are generally well tolerated and Streptococcus pneumoniae resistance remains low; however, rare but serious adverse effects have been reported. Some members of the fluoroquinolone class have been removed from the market amidst safety concerns. Pneumonia classifications have changed and antipseudomonal fluoroquinolones may have a role in healthcare-associated pneumonia when administered in combination with other antipseudomonal and anti-methicillin-resistant Staphylococcus aureus therapies.