Arianna Miles-Jay

Incidence Rate of Fluoroquinolone-Resistant Gram-Negative Rod Bacteremia among Allogeneic Hematopoietic Cell Transplantation Patients during an Era of Levofloxacin Prophylaxis

There are concerns that emerging resistance to fluoroquinolones (FQ) may be leading to increasing rates of gram-negative rod (GNR) bacteremia in hematopoietic cell transplant (HCT) recipients. We set out to describe time trends in the incidence rates of GNR bacteremia and FQ-resistant GNR bacteremia in HCT recipients during an era of levofloxacin prophylaxis. We conducted a longitudinal retrospective study of adults undergoing allogeneic HCT between 2003 and 2012 at the Seattle Cancer Care Alliance (SCCA). Annual trends in the incidence rates of GNR bacteremia and FQ-resistant GNR bacteremia through 100 days after transplantation were assessed using Poisson regression. Cox proportional hazards regression was used to compare 30-day mortality between patients with FQ-resistant and those with FQ-sensitive GNR bacteremia. Of the 2306 patients included in this cohort, 280 (12.1%) had GNR bacteremia. The incidence rates of GNR bacteremia and FQ-resistant GNR bacteremia increased from 2003 to 2009 and decreased afterwards; however, the overall annual trends were not significant (incidence rate ratio [IRR], 1.01; 95% confidence interval [CI], .98 to 1.05; IRR, 1.01; 95% CI, .95 to 1.08, respectively). FQ-resistant GNR bacteremia was associated with increased mortality compared with FQ-sensitive GNR bacteremia, even after adjustment for underlying disease severity, conditioning regimen, and age at transplantation (hazard ratio, 2.11; 95% CI, 1.06 to 4.23). On average, rates of FQ-resistant GNR bacteremia have not significantly changed over 10 years of FQ prophylaxis, although FQ-resistant GNR bacteremia is associated with increased mortality compared with FQ-sensitive GNR bacteremia.

Previous Antibiotic Exposure Increases Risk of Infection with Extended-Spectrum-β-Lactamase- and AmpC-Producing Escherichia coli and Klebsiella pneumoniae in Pediatric Patients.

ABSTRACT 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.

Evaluation of routine pretransplantation screening for methicillin-resistant Staphylococcus aureus in hematopoietic cell transplant recipients

Methicillin-resistant Staphylococcus aureus (MRSA) screening guidelines for hematopoietic cell transplant (HCT) recipients are not well defined. Retrospective assessment of standardized pretransplantation MRSA screening in a large single-center cohort of HCT recipients demonstrated that colonization was uncommon, and that no colonized patients developed posttransplantation invasive complications.

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 <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.

Use of Antibiotics Reserved for Resistant Gram-Negative Infections at Freestanding U.S. Children's Hospitals from 2004 to 2014.

We used the Pediatric Health Information System database to assess the use of antibiotics reserved for the treatment of resistant Gram-negative infections in children from 2004 to 2014. Overall, use of these agents increased in children from 2004 to 2007 and subsequently decreased. Infect Control Hosp Epidemiol 2016:37:967-970.

Epidemiology and Antimicrobial Resistance Characteristics of the Sequence Type 131-H30 Subclone Among Extraintestinal Escherichia coli Collected From US Children

Background Escherichia coli sequence type (ST) 131-H30 is a globally important pathogen implicated in rising rates of multidrug resistance among E. coli causing extraintestinal infections. Previous studies have focused on adults, leaving the epidemiology of H30 among children undefined. Methods We used clinical data and isolates from a case-control study of extended-spectrum cephalosporin-resistant E. coli conducted at 4 US childrens hospitals to estimate the burden and identify host correlates of infection with H30. H30 isolates were identified using 2-locus genotyping; host correlates were examined using log-binomial regression models stratified by extended-spectrum cephalosporin resistance status. Results A total of 339 extended-spectrum cephalosporin-resistant and 1008 extended-spectrum cephalosporin-susceptible E. coli isolates were available for analyses. The estimated period prevalence of H30 was 5.3% among all extraintestinal E. coli isolates (95% confidence interval [CI], 4.6%-7.1%); H30 made up 43.3% (81/187) of extended-spectrum β-lactamase (ESBL)-producing isolates in this study. Host correlates of infection with H30 differed by extended-spectrum cephalosporin resistance status: Among resistant isolates, age ≤5 years was positively associated with H30 infection (relative risk [RR], 1.83 [95% CI, 1.19-2.83]); among susceptible isolates, age ≤5 years was negatively associated with H30 (RR, 0.48 [95% CI, .27-.87]), while presence of an underlying medical condition was positively associated (RR, 4.49 [95% CI, 2.43-8.31]). Conclusions ST131-H30 is less common among extraintestinal E. coli collected from children compared to reported estimates among adults, possibly reflecting infrequent fluoroquinolone use in pediatrics; however, it is similarly dominant among ESBL-producing isolates. The H30 subclone appears to disproportionately affect young children relative to other extended-spectrum cephalosporin-resistant E. coli.

Epidemiology of the multidrug-resistant ST131-H30 subclone among extraintestinal Escherichia coli collected from US children

Background E. coli ST131-H30 is a globally important pathogen implicated in rising rates of multidrug resistance among E. coli causing extraintestinal infections. Previous studies have focused on adults, leaving the epidemiology of H30 among children undefined. Methods We used clinical data and isolates from a case-control study of extended-spectrum cephalosporin-resistant E. coli conducted at four US children’s hospitals to estimate the burden and identify host correlates of infection with H30. H30 isolates were identified using two-locus genotyping; host correlates were examined using log-binomial regression models stratified by extended-spectrum cephalosporin resistance status. Results A total of 339 extended-spectrum cephalosporin-resistant and 1008 extended-spectrum cephalosporin-susceptible E. coli isolates were available for analyses. The estimated period prevalence of H30 was 5.3% among all extraintestinal E. coli isolates (95% confidence interval [CI] 4.6%-7.1%); H30 made up 43.3% (81/187) of ESBL-producing isolates in this study. Host correlates of infection with H30 differed by extended-spectrum cephalosporin resistance status: among resistant isolates, age ≤5 years was positively associated with H30 infection (relative risk [RR] 1.83, 95% CI 1.19-2.83); among susceptible isolates, age ≤5 years was negatively associated with H30 (RR 0.48, 95% CI 0.27-0.87), while presence of an underlying medical condition was positively associated (RR 4.49, 95% CI 2.43-8.31). Conclusions ST131-H30 is less common among extraintestinal E. coli collected from children compared to reported estimates among adults, possibly reflecting infrequent fluoroquinolone use in pediatrics; however, it is similarly dominant among ESBL-producing isolates. The H30 subclone appears to disproportionately affect young children relative to other extendedspectrum cephalosporin-resistant E. coli. Summary ST131-H30 was responsible for 5.3% of all extraintestinal E. coli infections and 43.3% of ESBL-producing extraintestinal E. coli infections among US children. The clinical and demographic correlates of infection with ST131-H30 differed between extended-spectrum cephalosporin-resistant and -sensitive isolates.