Bacterial infections in neonates following mupirocin-based MRSA decolonization: A multicenter cohort study

OBJECTIVETo characterize the risk of infection after MRSA decolonization with intranasal mupirocin.DESIGNMulticenter, retrospective cohort study.SETTINGTertiary care neonatal intensive care units (NICUs) from 3 urban hospitals in the United States ranging in size from 45 to 100 beds.METHODSMRSA-colonized neonates were identified from NICU admissions occurring from January 2007 to December 2014, during which a targeted decolonization strategy was used for MRSA control. In 2 time-to-event analyses, MRSA-colonized neonates were observed from the date of the first MRSA-positive surveillance screen until (1) the first occurrence of novel gram-positive cocci in sterile culture or discharge or (2) the first occurrence of novel gram-negative bacilli in sterile culture or discharge. Mupirocin exposure was treated as time varying.RESULTSA total of 522 MRSA-colonized neonates were identified from 16,144 neonates admitted to site NICUs. Of the MRSA-colonized neonates, 384 (74%) received mupirocin. Average time from positive culture to mupirocin treatment was 3.5 days (standard deviation, 7.2 days). The adjusted hazard of gram-positive cocci infection was 64% lower among mupirocin-exposed versus mupirocin-unexposed neonates (hazard ratio, 0.36; 95% confidence interval [CI], 0.17–0.76), whereas the adjusted hazard ratio of gram-negative bacilli infection comparing mupirocin-exposed and -unexposed neonates was 1.05 (95% CI, 0.42–2.62).CONCLUSIONSIn this multicentered cohort of MRSA-colonized neonates, mupirocin-based decolonization treatment appeared to decrease the risk of infection with select gram-positive organisms as intended, and the treatment was not significantly associated with risk of subsequent infections with organisms not covered by mupirocin’s spectrum of activity.Infect Control Hosp Epidemiol2017;38:930–936</jats:sec

Antibiotic prophylaxis is associated with subsequent resistant infections in children with an initial extended-spectrum-cephalosporin-resistant Enterobacteriaceae infection

ABSTRACT The objective of this study was to assess the association between previous antibiotic use, particularly long-term prophylaxis, and the occurrence of subsequent resistant infections in children with index infections due to extended-spectrum-cephalosporin-resistant Enterobacteriaceae . We also investigated the concordance of the index and subsequent isolates. Extended-spectrum-cephalosporin-resistant Escherichia coli and Klebsiella spp. isolated from normally sterile sites of patients aged &lt;22 years were collected along with associated clinical data from four freestanding pediatric centers. Subsequent isolates were categorized as concordant if the species, resistance determinants, and fumC-fimH ( E. coli ) or tonB ( Klebsiella pneumoniae ) type were identical to those of the index isolate. In total, 323 patients had 396 resistant isolates; 45 (14%) patients had ≥1 subsequent resistant infection, totaling 73 subsequent resistant isolates. The median time between the index and first subsequent infections was 123 (interquartile range, 43 to 225) days. In multivariable Cox proportional hazards analyses, patients were 2.07 times as likely to have a subsequent resistant infection (95% confidence interval, 1.11 to 3.87) if they received prophylaxis in the 30 days prior to the index infection. In 26 (58%) patients, all subsequent isolates were concordant with their index isolate, and 7 (16%) additional patients had at least 1 concordant subsequent isolate. In 12 of 17 (71%) patients with E. coli sequence type 131 (ST131)-associated type 40-30, all subsequent isolates were concordant. Subsequent extended-spectrum-cephalosporin-resistant infections are relatively frequent and are most commonly due to bacterial strains concordant with the index isolate. Further study is needed to assess the role prophylaxis plays in these resistant infections. </jats:p

Metagenomic approach for identification of the pathogens associated with diarrhea in stool specimens

The potential to rapidly capture the entire microbial community structure and/or gene content makes metagenomic sequencing an attractive tool for pathogen identification and the detection of resistance/virulence genes in clinical settings. Here, we assessed the consistency between PCR from a diagnostic laboratory, quantitative PCR (qPCR) from a research laboratory, 16S rRNA gene sequencing, and metagenomic shotgun sequencing (MSS) for Clostridium difficile identification in diarrhea stool samples. Twenty-two C. difficile-positive diarrhea samples identified by PCR and qPCR and five C. difficile-negative diarrhea controls were studied. C. difficile was detected in 90.9% of C. difficile-positive samples using 16S rRNA gene sequencing, and C. difficile was detected in 86.3% of C. difficile-positive samples using MSS. CFU inferred from qPCR analysis were positively correlated with the relative abundance of C. difficile from 16S rRNA gene sequencing (r(2) = -0.60) and MSS (r(2) = -0.55). C. difficile was codetected with Clostridium perfringens, norovirus, sapovirus, parechovirus, and anellovirus in 3.7% to 27.3% of the samples. A high load of Candida spp. was found in a symptomatic control sample in which no causative agents for diarrhea were identified in routine clinical testing. Beta-lactamase and tetracycline resistance genes were the most prevalent (25.9%) antibiotic resistance genes in these samples. In summary, the proof-of-concept study demonstrated that next-generation sequencing (NGS) in pathogen detection is moderately correlated with laboratory testing and is advantageous in detecting pathogens without a priori knowledge. J Clin Microbiol 2016 Feb; 54(2):368-75

Previous antibiotic exposure increases risk of infection with extended-spectrum-β-lactamase- and AmpC-producing Escherichia coli and Klebsiella pneumoniae in pediatric patients

The objective of this study was to determine whether antibiotic exposure is associated with extended-spectrum-beta-lactamase- or AmpC-producing Escherichia coli or Klebsiella pneumoniae infections in children. We collected extended-spectrum-beta-lactamase- or AmpC-producing E. coli or K. pneumoniae isolates and same-species susceptible controls from normally sterile sites of patients aged ≤21 years, along with associated clinical data, at four free-standing pediatric centers. After controlling for potential confounders, the relative risk of having an extended-spectrum-beta-lactamase-producing isolate rather than a susceptible isolate was 2.2 times higher (95% confidence interval [CI], 1.49 to 3.35) among those with antibiotic exposure in the 30 days prior to infection than in those with no antibiotic exposure. The results were similar when analyses were limited to exposure to third-generation cephalosporins, other broad-spectrum beta-lactams, or trimethoprim-sulfamethoxazole. Conversely, the relative risk of having an AmpC-producing versus a susceptible isolate was not significantly elevated with any antibiotic exposure in the 30 days prior to infection (adjusted relative risk ratio, 1.12; 95% CI, 0.65 to 1.91). However, when examining subgroups of antibiotics, the relative risk of having an AmpC-producing isolate was higher for patients with exposure to third-generation cephalosporins (adjusted relative risk ratio, 4.48; 95% CI, 1.75 to 11.43). Dose-response relationships between antibiotic exposure and extended-spectrum-beta-lactamase-producing or AmpC-producing isolates were not demonstrated. These results reinforce the need to study and implement pediatric antimicrobial stewardship strategies, and they indicate that epidemiological studies of third-generation cephalosporin-resistant E. coli and K. pneumoniae isolates should include resistance mechanisms when possible