Prolonged-course Antibiotic Therapy Research Articles

The remaining unsolved problems for rational antibiotic therapy use in pediatric community-acquired pneumonia

ABSTRACT Introduction Despite availability of several official guidelines, not all the problems related to the most effective and safe use of antibiotics in children with community-acquired pneumonia (CAP) have been solved. Presently, too many children receive unneeded antibiotics or, when antibiotics are mandatory, the choice of the drug is not appropriate. Areas covered In this paper, the authors discuss the remaining unsolved problems for rational antibiotic therapy use in pediatric community-acquired pneumonia and provide their expert perspectives. Expert opinion Further improvement in pediatric CAP management could be derived from physician education on antibiotic use and a larger use, particularly in office practice, of point of care testing or new technologies (i.e. artificial intelligence) to define etiology of a lower respiratory infection. However, recommendations regarding the duration of antibiotic therapy vary largely because of the absence of reliable data on the optimal CAP treatment according to the bacterial etiology of the disease, its severity, and child characteristics. Available evidence seems to confirm that a short course of antibiotics, approximately 5 days, can be effective and lead to results not substantially different from those obtained with prolonged-course antibiotic therapy, at least in patients with mild to moderate disease.

Short- versus prolonged-course antibiotic therapy for sepsis or infectious diseases in critically ill adults: a systematic review and meta-analysis

Background The 2016 International Guidelines for the Management of Sepsis and Septic Shock recommend antibiotic therapy for 7–10 days for most patients with sepsis. However, evidence on critically ill patients is limited. Thus, we conducted the first systematic review and meta-analysis comparing the effectiveness and adverse events of shorter- (≤1 week) with longer-course antibiotics in adults with critical infections including sepsis. Methods We searched the MEDLINE, Cochrane Central Register of Controlled Trials, and Igaku Chuo Zasshi databases for randomised controlled trials (RCTs) and observational studies (OSs) from inception to 31 March 2021. Results We included 6 of 3,766 identified articles, incorporating data from 4 RCTs and 2 OSs (1,721 patients) in meta-analyses. Three RCTs and one OS focussed on ventilator-associated pneumonia, and one RCT and one OS investigated intra-abdominal infections. The severity score levels were similar to that of sepsis, but no study comprehensively focussing on sepsis was found. There were no significant differences in mortality at a maximum follow-up of 30 days (RR 1.08, 95%CI 0.80–1.46); 28-day mortality, clinical cure, the occurrence of new events, and the emergence of resistant organisms between the groups in the RCTs. The OSs findings were consistent. The quality of evidence was assessed as very low to moderate using the GRADE approach, with no uniform description of severity scores, sepsis, or adverse events. Conclusions Shorter, fixed-duration antibiotic therapy for clinically heterogeneous sepsis or severe infections was not associated with poorer outcomes, but the overall quality of evidence was poor.

The Association of Antibiotic Duration With Successful Treatment of Community-Acquired Pneumonia in Children.

National guidelines recommend 10 days of antibiotics for children with community-acquired pneumonia (CAP), acknowledging that the outcomes of children hospitalized with CAP who receive shorter durations of therapy have not been evaluated. We conducted a comparative effectiveness study of children aged ≥6 months hospitalized at The Johns Hopkins Hospital who received short-course (5-7 days) vs prolonged-course (8-14 days) antibiotic therapy for uncomplicated CAP between 2012 and 2018 using an inverse probability of treatment weighted propensity score analysis. Inclusion was limited to children with clinical and radiographic criteria consistent with CAP, as adjudicated by 2 infectious diseases physicians. Children with tracheostomies; healthcare-associated, hospital-acquired, or ventilator-associated pneumonia; loculated or moderate to large pleural effusion or pulmonary abscess; intensive care unit stay >48 hours; cystic fibrosis/bronchiectasis; severe immunosuppression; or unusual pathogens were excluded. The primary outcome was treatment failure, a composite of unanticipated emergency department visits, outpatient visits, hospital readmissions, or death (all determined to be likely attributable to bacterial pneumonia) within 30 days after completing antibiotic therapy. Four hundred and thirty-nine patients met eligibility criteria; 168 (38%) patients received short-course therapy (median, 6 days) and 271 (62%) received prolonged-course therapy (median, 10 days). Four percent of children experienced treatment failure, with no differences observed between patients who received short-course vs prolonged-course antibiotic therapy (odds ratio, 0.48; 95% confidence interval, .18-1.30). A short course of antibiotic therapy (approximately 5 days) does not increase the odds of 30-day treatment failure compared with longer courses for hospitalized children with uncomplicated CAP.

212. Outcomes of Adults with Uncomplicated Staphylococcus aureus Bacteremia Receiving Short-Course Vs. Prolonged-Course Antibiotic Therapy in a Multicenter, Propensity Score–Matched Cohort

BackgroundThe recommended duration of antibiotic treatment for uncomplicated Staphylococcus aureus bloodstream infections is 14 days. We compared the outcomes of patients receiving short-course (6–10 days) vs. prolonged-course (11–16 days) antibiotic therapy for S. aureus bacteremia (SAB).Methods30-day outcome of patients with penicillin (PSSAB, n = 202)) or methicillin-susceptible SAB (MSSAB, n = 203) treated with in vitro active therapy in the range of 6–16 days was analyzed using pooled data from two previously published, observational studies. Individuals were matched 1:1 by nearest neighbor propensity score matching without replacement. Regression analysis was performed to estimate the risk of all-cause mortality within 30 days after the end of antibiotic treatment. Eligible individuals had to have >1 day of follow-up after discontinuation of antimicrobials. Individuals with a diagnosis of endocarditis, bone infection, meningitis or pneumonia were excluded.ResultsThere were 107 well-balanced matched pairs; 58 in the PSSAB and 39 in the MSSAB cohort. For PSSAB, the median duration of therapy was 8 (interquartile range [IQR], 7–10) in the short-course group and 12 days (IQR, 10–13) in the prolonged-course group. For the MSSAB cohort, these numbers were 9 days (IQR, 7–10) and 14 days (IQR, 13–16 days), respectively. No difference in mortality between short-course and prolonged-course treatment was observed (adjusted hazard ratio [aHR], 0.74; 95% confidence interval [CI], .23–2.41) and 1.14; 95% CI, 0.31–4.20), respectively for PSSAB and MSSAB.ConclusionShort courses of antibiotic therapy yielded similar clinical outcomes as prolonged courses of antibiotic therapy for S. aureus bacteremia. The findings warrant a randomized clinical trial to study the safety and efficacy of shortened antimicrobial therapy for the treatment of uncomplicated SAB. Disclosures All authors: No reported disclosures.

Impairment of Validity of Comparison Between Short-Course and Prolonged-Course Antibiotic Therapy Using Propensity Score Matching.

Impairment of Validity of Comparison Between Short-Course and Prolonged-Course Antibiotic Therapy Using Propensity Score Matching.

Comparing the Outcomes of Adults with Enterobacteriaceae Bacteremia Receiving Short-Course vs Prolonged-Course Antibiotic Therapy

BackgroundThe recommended duration of antibiotic treatment for Enterobacteriaceae bacteremia is between 7 and 14 days. We compared the clinical outcomes of patients receiving short-course (6–10 days) vs prolonged-course (11–15 days) antibiotic therapy for Enterobacteriaceae bacteremia.MethodsA retrospective cohort study was conducted at The Johns Hopkins Hospital, The University of Maryland Medical Center, and The Hospital of the University of Pennsylvania including patients with monomicrobial Enterobacteriaceae bacteremia treated with in vitro active antibiotic therapy in the range of 6–15 days between 2008 and 2014. 1:1 nearest neighbor propensity score matching without replacement was performed, prior to regression analysis, to estimate the risk of all-cause mortality within 30 days after the end of antibiotic treatment for patients receiving short vs. prolonged durations of antibiotic therapy. Secondary outcomes included Clostridium difficile infection (CDI) and the emergence of multidrug-resistant Gram-negative (MDRGN) bacteria within 30 days after the end of antibiotic therapy.ResultsA total of 1,769 patients met eligibility criteria. There were 385 matched pairs who were well-balanced on baseline characteristics. The median duration of therapy in the short-course group and prolonged-course group was 8 days (interquartile range (IQR) 7–9 days) and 15 days (IQR 13–15 days), respectively. No difference in all-cause mortality between short- and prolonged-course treatment groups was observed (adjusted hazard ratio [aHR] 1.00; 95% CI 0.62–1.63). Rates of CDI were similar between the treatment groups (OR 1.17; 95% CI 0.39–3.51). There was a non-significant protective effect of short-course antibiotic therapy on the emergence of MDRGN bacteria (OR 0.59; 95% CI 0.32–1.09 P = 0.09).ConclusionShort courses of antibiotic therapy yields similar clinical outcomes to prolonged courses of antibiotic therapy for Enterobacteriaceae bacteremia, and may protect against subsequent MDRGN emergence.Disclosures All authors: No reported disclosures.

Short-Course Versus Prolonged-Course Antibiotic Therapy for Hospital-Acquired Pneumonia in Critically Ill Adults.

Short-Course Versus Prolonged-Course Antibiotic Therapy for Hospital-Acquired Pneumonia in Critically Ill Adults.

Which regimen is most effective at improving outcomes in critically ill adults with hospital-acquired pneumonia: short-course or prolonged-course antibiotic therapy?

Which regimen is most effective at improving outcomes in critically ill adults with hospital-acquired pneumonia: short-course or prolonged-course antibiotic therapy?

Short-course versus prolonged-course antibiotic therapy for hospital-acquired pneumonia in critically ill adults.

Pneumonia is the most common hospital-acquired infection affecting patients in the intensive care unit (ICU). However, current national guidelines for the treatment of hospital-acquired pneumonia (HAP) are several years old and the diagnosis of pneumonia in mechanically ventilated patients (VAP) has been subject to considerable recent attention. The optimal duration of antibiotic therapy for HAP in the critically ill is uncertain. To assess the effectiveness of short versus prolonged-course antibiotics for HAP in critically ill adults, including patients with VAP. We searched CENTRAL (2015, Issue 5), MEDLINE (1946 to June 2015), MEDLINE in-process and other non-indexed citations (5 June 2015), EMBASE (2010 to June 2015), LILACS (1982 to June 2015) and Web of Science (1955 to June 2015). We considered all randomised controlled trials (RCTs) comparing a fixed 'short' duration of antibiotic therapy with a 'prolonged' course for HAP (including patients with VAP) in critically ill adults. Two review authors conducted data extraction and assessment of risk of bias. We contacted trial authors for additional information. We identified six relevant studies involving 1088 participants. This included two new studies published after the date of our previous review (2011). There was substantial variation in participants, in the diagnostic criteria used to define an episode of pneumonia, in the interventions and in the reported outcomes. We found no evidence relating to patients with a high probability of HAP who were not mechanically ventilated. For patients with VAP, overall a short seven- or eight-day course of antibiotics compared with a prolonged 10- to 15-day course increased 28-day antibiotic-free days (two studies; N = 431; mean difference (MD) 4.02 days; 95% confidence interval (CI) 2.26 to 5.78) and reduced recurrence of VAP due to multi-resistant organisms (one study; N = 110; odds ratio (OR) 0.44; 95% CI 0.21 to 0.95), without adversely affecting mortality and other recurrence outcomes. However, for cases of VAP specifically due to non-fermenting Gram-negative bacilli (NF-GNB), recurrence was greater after short-course therapy (two studies, N = 176; OR 2.18; 95% CI 1.14 to 4.16), though mortality outcomes were not significantly different. One study found that a three-day course of antibiotic therapy for patients with suspected HAP but a low Clinical Pulmonary Infection Score (CPIS) was associated with a significantly lower risk of superinfection or emergence of antimicrobial resistance, compared with standard (prolonged) course therapy. On the basis of a small number of studies and appreciating the lack of uniform definition of pneumonia, we conclude that for patients with VAP not due to NF-GNB a short, fixed course (seven or eight days) of antibiotic therapy appears not to increase the risk of adverse clinical outcomes, and may reduce the emergence of resistant organisms, compared with a prolonged course (10 to 15 days). However, for patients with VAP due to NF-GNB, there appears to be a higher risk of recurrence following short-course therapy. These findings do not differ from those of our previous review and are broadly consistent with current guidelines. There are few data from RCTs comparing durations of therapy in non-ventilated patients with HAP, but on the basis of a single study, short-course (three-day) therapy for HAP appears not to be associated with worse clinical outcome, and may reduce the risk of subsequent infection or the emergence of resistant organisms when there is low probability of pneumonia according to the CPIS.

Review: Short-course antibiotics in hospital-acquired pneumonia do not affect mortality

Source Citation Pugh R, Grant C, Cooke RP, Dempsey G. Short-course versus prolonged-course antibiotic therapy for hospital-acquired pneumonia in critically ill adults. Cochrane Database Syst Rev. 2...

Ventilator-Associated Tracheitis in Children: Does Antibiotic Duration Matter?

The optimal duration of antibiotic therapy for ventilator-associated tracheitis (VAT) has not been defined, which may result in unnecessarily prolonged courses of antibiotics. The primary objective of this study was to determine whether prolonged-course (≥7 days in duration) therapy for VAT was more protective against progression to hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP), compared with short-course antibiotics (<7 days in duration). The secondary objective was to determine whether prolonged-course therapy was more likely to result in the acquisition of multidrug-resistant organisms (MDROs) compared with short-course therapy. We conducted a retrospective cohort study of children ≤18 years of age hospitalized in the intensive care unit and intubated for ≥48 h from January 2007 through December 2009 who received antibiotic therapy for VAT. Of the 1616 patients intubated for at least 48 h, 150 received antibiotics for clinician-suspected VAT, although only 118 of these patients met VAT criteria. Prolonged-course antibiotics were not protective against subsequent development of HAP or VAP (hazard ratio [HR], 1.08; 95% confidence interval [CI], 0.40-2.91). Factors associated with subsequent MDRO colonization or infection included prolonged-course antibiotic therapy (HR, 5.15; 95% CI, 1.54-7.19), receipt of combination antibiotic therapy (HR, 3.24; 95% CI, 1.54-6.82), and days of hospital exposure prior to completing antibiotic therapy (HR, 1.08; 95% CI, 1.04-1.12). A prolonged course of antibiotics for VAT does not appear to protect against progression to HAP or VAP compared with short-course therapy. Furthermore, prolonged antibiotic courses were associated with a significantly increased risk of subsequent MDRO acquisition.