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Comparative effectiveness of antibiotic treatment strategies for pediatric skin and soft-tissue infections.

ABSTRACT: To compare the effectiveness of clindamycin, trimethoprim-sulfamethoxazole, and ?-lactams for the treatment of pediatric skin and soft-tissue infections (SSTIs).A retrospective cohort of children 0 to 17 years of age who were enrolled in Tennessee Medicaid, experienced an incident SSTI between 2004 and 2007, and received treatment with clindamycin (reference), trimethoprim-sulfamethoxazole, or a ?-lactam was created. Outcomes included treatment failure and recurrence, defined as an SSTI within 14 days and between 15 and 365 days after the incident SSTI, respectively. Adjusted models stratified according to drainage status were used to estimate the risk of treatment failure and time to recurrence.Among the 6407 children who underwent drainage, there were 568 treatment failures (8.9%) and 994 recurrences (22.8%). The adjusted odds ratios for treatment failure were 1.92 (95% confidence interval [CI]: 1.49-2.47) for trimethoprim-sulfamethoxazole and 2.23 (95% CI: 1.71-2.90) for ?-lactams. The adjusted hazard ratios for recurrence were 1.26 (95% CI: 1.06-1.49) for trimethoprim-sulfamethoxazole and 1.42 (95% CI: 1.19-1.69) for ?-lactams. Among the 41 094 children without a drainage procedure, there were 2435 treatment failures (5.9%) and 5436 recurrences (18.2%). The adjusted odds ratios for treatment failure were 1.67 (95% CI: 1.44-1.95) for trimethoprim-sulfamethoxazole and 1.22 (95% CI: 1.06-1.41) for ?-lactams; the adjusted hazard ratios for recurrence were 1.30 (95% CI: 1.18-1.44) for trimethoprim-sulfamethoxazole and 1.08 (95% CI: 0.99-1.18) for ?-lactams.Compared with clindamycin, use of trimethoprim-sulfamethoxazole or ?-lactams was associated with increased risks of treatment failure and recurrence. Associations were stronger for those with a drainage procedure.

SUBMITTER: Williams DJ

PROVIDER: S-EPMC3387880 | biostudies-other | 2011 Sep

REPOSITORIES: biostudies-other

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Comparative effectiveness of antibiotic treatment strategies for pediatric skin and soft-tissue infections.

Williams Derek J DJ Cooper William O WO Kaltenbach Lisa A LA Dudley Judith A JA Kirschke David L DL Jones Timothy F TF Arbogast Patrick G PG Griffin Marie R MR Creech C Buddy CB

Pediatrics 20110815 3

<h4>Objective</h4>To compare the effectiveness of clindamycin, trimethoprim-sulfamethoxazole, and β-lactams for the treatment of pediatric skin and soft-tissue infections (SSTIs).<h4>Methods</h4>A retrospective cohort of children 0 to 17 years of age who were enrolled in Tennessee Medicaid, experienced an incident SSTI between 2004 and 2007, and received treatment with clindamycin (reference), trimethoprim-sulfamethoxazole, or a β-lactam was created. Outcomes included treatment failure and recur ...[more]

PMID: 21844058

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Project description:BackgroundThe treatment of complicated skin and soft tissue infections (cSSTI) is challenging and many patients do not receive adequate first-line therapy. REACH (REtrospective Study to Assess the Clinical Management of Patients With Moderate-to-Severe cSSTI or Community-Acquired Pneumonia in the Hospital Setting) was a retrospective observational study of cSSTI patients in real-life settings in European hospitals. In this analysis, we review characteristics and outcomes of patients with an early response (≤72 hours) compared with those without an early response to treatment. We also compare the results according to two differing definitions of early response, one of which (Definition 1) requires resolution of fever within 72 hours, in line with previous US FDA guidelines.MethodsPatients were adults hospitalized with cSSTIs 2010-2011 and requiring treatment with intravenous antibiotics. Clinical management, clinical outcomes and healthcare resource use were assessed using a descriptive analysis approach.ResultsThe analysis set included 600 patients, of which 363 showed early response with Definition 1 and 417 with Definition 2. Initial treatment modification was frequent, and highest in patients without early response (48.1% with Definition 1). Patients without early response were more likely to have diabetes than those with early response (31.6% vs. 22.9%, respectively) and to suffer from more severe disease (e.g. skin necrosis: 14.8% and 7.7%, respectively), to be infected with difficult-to-treat microorganisms and to have recurrent infections. Furthermore, patients without early response had a higher rate of adverse clinical outcomes (e.g. septic shock) and higher use of healthcare resources. The results obtained with the two definitions for early response were largely similar.ConclusionsThis study highlights the significance of early evaluation of patients in hospitals, in potentially preventing prolonged use of inappropriate or ineffective antibacterial therapy.Trial registrationNCT01293435 .

Project description:Escherichia coli, an intestinal Gram-negative bacterium, has been shown to be associated with a variety of diseases in addition to intestinal infections, such as urinary tract infections (UTIs), meningitis in neonates, septicemia, skin and soft tissue infections (SSTIs), and colisepticemia. Thus, for nonintestinal infections, it is categorized as extraintestinal pathogenic E. coli (ExPEC). It is also an opportunistic pathogen, causing cross infections, notably as an agent of zoonotic diseases. However, comparative genomic data providing functional and genetic coordinates for ExPEC strains associated with these different types of infections have not proven conclusive. In the study reported here, ExPEC E. coli isolated from SSTIs was characterized, including virulence and drug resistance profiles, and compared with isolates from patients suffering either pyelonephritis or septicemia. Results revealed that the majority of the isolates belonged to two pathogenic phylogroups, B2 and D. Approximately 67% of the isolates were multidrug resistant (MDR), with 85% producing extended-spectrum beta-lactamase (ESBL) and 6% producing metallo-beta-lactamase (MBL). The blaCTX-M-15 genotype was observed in at least 70% of the E. coli isolates in each category, conferring resistance to an extended range of beta-lactam antibiotics. Whole-genome sequencing and comparative genomics of the ExPEC isolates revealed that two of the four isolates from SSTIs, NA633 and NA643, belong to pandemic sequence type ST131, whereas functional characteristics of three of the ExPEC pathotypes revealed that they had equal capabilities to form biofilm and were resistant to human serum. Overall, the isolates from a variety of ExPEC infections demonstrated similar resistomes and virulomes and did not display any disease-specific functional or genetic coordinates.IMPORTANCE Infections caused by extraintestinal pathogenic E. coli (ExPEC) are of global concern as they result in significant costs to health care facilities management. The recent emergence of a multidrug-resistant pandemic clone, Escherichia coli ST131, is of primary concern as a global threat. In developing countries, such as India, skin and soft tissue infections (SSTIs) associated with E. coli are marginally addressed. In this study, we employed both genomic analysis and phenotypic assays to determine relationships, if any, among the ExPEC pathotypes. Similarity between antibiotic resistance and virulence profiles was observed, ST131 isolates from SSTIs were reported, and genomic similarities among strains isolated from different disease conditions were detected. This study provides functional molecular infection epidemiology insight into SSTI-associated E. coli compared with ExPEC pathotypes.

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Comparative effectiveness of antibiotic treatment strategies for pediatric skin and soft-tissue infections.

Publications

Comparative effectiveness of antibiotic treatment strategies for pediatric skin and soft-tissue infections.

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