Search

Background The epidemiology of extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) in low- and middle-income countries (LMICs) is poorly described. Identifying risk factors for ESCrE colonization is critical to inform antibiotic resistance reduction strategies because colonization is typically a precursor to infection. Methods From 15 January 2020 to 4 September 2020, we surveyed a random sample of clinic patients at 6 sites in Botswana. We also invited each enrolled participant to refer up to 3 adults and children. All participants had rectal swabs collected that were inoculated onto chromogenic media followed by confirmatory testing. Data were collected on demographics, comorbidities, antibiotic use, healthcare exposures, travel, and farm and animal contact. Participants with ESCrE colonization (cases) were compared with noncolonized participants (controls) to identify risk factors for ESCrE colonization using bivariable, stratified, and multivariable analyses. Results A total of 2000 participants were enrolled. There were 959 (48.0%) clinic participants, 477 (23.9%) adult community participants, and 564 (28.2%) child community participants. The median (interquartile range) age was 30 (12–41) and 1463 (73%) were women. There were 555 cases and 1445 controls (ie, 27.8% of participants were ESCrE colonized). Independent risk factors (adjusted odds ratio [95% confidence interval]) for ESCrE included healthcare exposure (1.37 [1.08–1.73]), foreign travel [1.98 (1.04–3.77]), tending livestock (1.34 [1.03–1.73]), and presence of an ESCrE-colonized household member (1.57 [1.08–2.27]). Conclusions Our results suggest healthcare exposure may be important in driving ESCrE. The strong links to livestock exposure and household member ESCrE colonization highlight the potential role of common exposure or household transmission. These findings are critical to inform strategies to curb further emergence of ESCrE in LMICs. [ABSTRACT FROM AUTHOR]

Background Klebsiella species, including the notable pathogen K. pneumoniae , are increasingly associated with antimicrobial resistance (AMR). Genome-based surveillance can inform interventions aimed at controlling AMR. However, its widespread implementation requires tools to streamline bioinformatic analyses and public health reporting. Methods We developed the web application Pathogenwatch, which implements analytics tailored to Klebsiella species for integration and visualization of genomic and epidemiological data. We populated Pathogenwatch with 16 537 public Klebsiella genomes to enable contextualization of user genomes. We demonstrated its features with 1636 genomes from 4 low- and middle-income countries (LMICs) participating in the NIHR Global Health Research Unit (GHRU) on AMR. Results Using Pathogenwatch, we found that GHRU genomes were dominated by a small number of epidemic drug-resistant clones of K. pneumoniae. However, differences in their distribution were observed (eg, ST258/512 dominated in Colombia, ST231 in India, ST307 in Nigeria, ST147 in the Philippines). Phylogenetic analyses including public genomes for contextualization enabled retrospective monitoring of their spread. In particular, we identified hospital outbreaks, detected introductions from abroad, and uncovered clonal expansions associated with resistance and virulence genes. Assessment of loci encoding O-antigens and capsule in K. pneumoniae , which represent possible vaccine candidates, showed that 3 O-types (O1–O3) represented 88.9% of all genomes, whereas capsule types were much more diverse. Conclusions Pathogenwatch provides a free, accessible platform for real-time analysis of Klebsiella genomes to aid surveillance at local, national, and global levels. We have improved representation of genomes from GHRU participant countries, further facilitating ongoing surveillance. [ABSTRACT FROM AUTHOR]

Background Quinolone resistance has been documented in the pediatric population, although their use is limited in children. This study investigated the effect of maternal quinolone use on gram-negative bacterial resistance to quinolones in their offspring. Methods We conducted a population-based, unmatched case-control study during 2010–2017. Cases were all children aged 0.5–17 years with community acquired, gram-negative quinolone-resistant bacteriuria. Controls were similar children with quinolone-sensitive bacteriuria. Only the first positive urine cultures for each child were included. Data on quinolones dispensed to the mother, any antibiotics dispensed to the children, age, sex, ethnicity, and prior hospitalizations were collected. Children with previous quinolone use were excluded. Results The study population consisted of 40 204 children. Quinolone resistance was detected in 2182 (5.3%) urine cultures. The median age was 5 years, with 93.7% females and 77.6% Jewish. A total of 26 937 (65%) of the children received any antibiotic and 1359 (3.2%) of the mothers received quinolones in the 6 months preceding bacteriuria. Independent risk factors were quinolone dispensed to the mothers (odds ratio [OR], 1.50 [95% confidence interval {CI}, 1.22–1.85]), Arab ethnicity (OR, 1.99 [95% CI, 1.81–2.19]), and antibiotic dispensed to the child (OR, 1.54 [95% CI, 1.38–1.71]). Compared with children aged 12–17 years, younger children had 1.33–1.43 increased odds for quinolone-resistant bacteriuria. Conclusions Quinolone prescription to mothers was linked to increased risk of community-acquired, quinolone-resistant bacteria in their offspring, by about 50%. This is another example of the deleterious ecological effects of antibiotic use and should be considered when prescribing antibiotics. [ABSTRACT FROM AUTHOR]

Background Carbapenem-resistant Pseudomonas aeruginosa (CRPA) colonizes the gastrointestinal tract of intensive care unit (ICU) patients, and CRPA colonization puts patients at increased risk of CRPA infection. Prior studies have not examined relationships between the microbiota, medications, and CRPA colonization acquisition. Methods Data and perirectal swabs were obtained from a cohort of ICU patients at the University of Maryland Medical Center. Patients (N = 109) were classified into 3 groups by CRPA colonization-acquisition status and antimicrobial exposure. We conducted 16S ribosomal RNA gene sequencing of an ICU admission swab and ≥1 additional swab and evaluated associations between patient characteristics, medications, the gastrointestinal microbiota, and CRPA colonization acquisition. Results ICU patients had low levels of diversity and high relative abundances of pathobionts. Piperacillin-tazobactam was prescribed more frequently to patients with CRPA colonization acquisition than those without. Piperacillin-tazobactam was associated with low abundance of potentially protective taxa (eg, Lactobacillus and Clostridiales) and increased risk of Enterococcus domination (odds ratio [OR], 5.50; 95% confidence interval [CI], 2.03–14.92). Opioids were associated with dysbiosis in patients who did not receive antibiotics; potentially protective Blautia and Lactobacillus were higher in patients who did not receive opioids. Several correlated taxa, identified at ICU admission, were associated with lower risk of CRPA colonization acquisition (OR, 0.58; 95% CI,.38–.87). Conclusions Antibiotics differed in their impact on the microbiota, with piperacillin-tazobactam being particularly damaging. Certain bacterial taxa (eg, Clostridiales) were negatively associated with CRPA colonization acquisition. These taxa may be markers of risk for CRPA colonization acquisition and/or serve a protective role. [ABSTRACT FROM AUTHOR]

Background An association between increased relative abundance of specific bacterial taxa in the intestinal microbiota and bacteremia has been reported in some high-risk patient populations. Methods We collected weekly rectal swab samples from patients at 1 long-term acute care hospital (LTACH) in Chicago from May 2015 to May 2016. Samples positive for Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) by polymerase chain reaction and culture underwent 16S rRNA gene sequence analysis; relative abundance of the operational taxonomic unit containing KPC-Kp was determined. Receiver operator characteristic (ROC) curves were constructed using results from the sample with highest relative abundance of KPC-Kp from each patient admission, excluding samples collected after KPC-Kp bacteremia. Cox regression analysis was performed to evaluate risk factors associated with time to achieve KPC-Kp relative abundance thresholds calculated by ROC curve analysis. Results We collected 2319 samples from 562 admissions (506 patients); KPC-Kp colonization was detected in 255 (45.4%) admissions and KPC-Kp bacteremia in 11 (4.3%). A relative abundance cutoff of 22% predicted KPC-Kp bacteremia with sensitivity 73%, specificity 72%, and relative risk 4.2 (P =.01). In a multivariable Cox regression model adjusted for age, Charlson comorbidity index, and medical devices, carbapenem receipt was associated with achieving the 22% relative abundance threshold (P =.044). Conclusion Carbapenem receipt was associated with increased hazard for high relative abundance of KPC-Kp in the gut microbiota. Increased relative abundance of KPC-Kp was associated with KPC-Kp bacteremia. Whether bacteremia arose directly from bacterial translocation or indirectly from skin contamination followed by bloodstream invasion remains to be determined. [ABSTRACT FROM AUTHOR]

Background Long-term care facilities (LTCFs) are a major reservoir of carbapenem-resistant Enterobacteriaceae (CRE) in healthcare facilities, contributing to rapid regional dissemination of CRE. Methods In 2008, The Israeli National Center for Infection Control (NCIC) initiated a coordinated, comprehensive intervention in Israel's LTCFs, encompassing approximately 25000 beds in over 300 institutions. The intervention included implementation of population-tailored contact precautions and early detection of carriers. The NCIC established a real-time repository of all CRE carriers and events of acquisition, supervised information exchange between healthcare facilities and directed intervention at the institutional level during local outbreaks. CRE incidence was determined based on detection of CRE, either during LTFC stay or on admission to another facility. Prevalence was determined by a series of 5 cross-sectional surveys commenced between 2008 and 2015. Results From January 2009 through December 2015, 5265 patients acquired CRE in LTCFs. During the study period, incidence of acquisition declined in all facility types, to approximately 50% of the baseline (P <.001). The number of skilled nursing facilities and nursing homes experiencing ≥ 5 CRE acquisitions annually decreased from 35 to 11 during this period. The point prevalence of newly detected CRE carriage in post-acute care hospitals decreased from 12.3% in the survey commenced in 2008 to 0.8% in that begun in 2015 (P <.001). Conclusions A national, coordinated intervention resulted in a sustained decrease in CRE incidence and prevalence in LTCFs. These results support the assumption that centrally coordinated intervention is an essential public health tool in reducing CRE in healthcare facilities. [ABSTRACT FROM AUTHOR]

Background. Patients hospitalized with hematologic malignancy are particularly vulnerable to infection. The impact of reported beta-lactam (BL) allergy in this population remains unknown. Methods. This was a retrospective cohort study of adult inpatients with hematologic malignancy admitted at 2 tertiary care hospitals from 2010 through 2015. The primary outcome was hospital length of stay (LOS) after administration of the first antibiotic. Secondary outcomes included readmission, mortality, complications, hospital charges, and antibiotic usage. Our goal was to define the impact of BL-only allergy (BLOA) label on clinical outcomes compared to those with no BL allergy (NBLA) in hematologic malignancy inpatients who required systemic antibiotics. Results. In our cohort (n = 4671), 38.3% had leukemia, 4.9% had Hodgkin lymphoma, 36.1% had non-Hodgkin lymphoma, and 20.7% had multiple myeloma. Among patients, 35.1% reported antibiotic allergy, and 14.1% (n = 660) had BLOA (including 9.3% with penicillin-only allergy and 3.3% cephalosporin-only allergy). Patients with BLOA had longer median LOS compared to patients with NBLA (11.3 vs 7.6 days, P < .001), which remained significant after multivariable adjustment. Patients with BLOA also had significantly worse outcomes in terms of mortality rate at 30 days (7.6% vs 5.3%, P = .017) and 180 days (15.8% vs 12.2%, P = .013), 30-day readmission rate, Clostridium difficile rate, hospital charges ($223 046 vs $173 256, P < .001), antibiotic classes used, and antibiotic duration. Conclusions. In hospitalized patients with hematologic malignancy, patients with reported BL allergy had worse clinical outcomes and higher healthcare cost than those without BL allergy label. [ABSTRACT FROM AUTHOR]

Background. Enteral and respiratory tract colonization with gram-negative bacteria may lead to subsequent infections in critically ill patients. We aimed to clarify the interdependence between gut and respiratory tract colonization and their associations with intensive care unit (ICU)-acquired infections in patients receiving selective digestive tract decontamination (SDD). Methods. Colonization status of the rectum and respiratory tract was determined using twice-weekly microbiological surveillance in mechanically ventilated subjects receiving SDD between May 2011 and June 2015 in a tertiary medical-surgical ICU in the Netherlands. Acquisition of infections was monitored daily by dedicated observers. Marginal structural models were used to determine the associations between gram-negative rectal colonization and respiratory tract colonization, ICU-acquired gram-negative infection, and ICU-acquired gram-negative bacteremia. Results. Among 2066 ICU admissions, 1157 (56.0%) ever had documented gram-negative carriage in the rectum during ICU stay. Cumulative incidences of ICU-acquired gram-negative infection and bacteremia were 6.0% (n = 124) and 2.1% (n = 44), respectively. Rectal colonization was an independent risk factor for both respiratory tract colonization (cause-specific hazard ratio [CSHR], 2.93 [95% confidence interval {CI}, 2.02-4.23]) and new gram-negative infection in the ICU (CSHR, 3.04 [95% CI, 1.99-4.65]). Both rectal and respiratory tract colonization were associated with bacteremia (CSHR, 7.37 [95% CI, 3.25-16.68] and 2.56 [95% CI, 1.9-6.03], respectively). Similar associations were observed when Enterobacteriaceae and glucose nonfermenting gram-negative bacteria were analyzed separately. Conclusions. Gram-negative rectal colonization tends to be stronger associated with subsequent ICU-acquired gram-negative infections than gram-negative respiratory tract colonization. Gram-negative rectal colonization seems hardly associated with subsequent ICU-acquired gram-negative respiratory tract colonization. [ABSTRACT FROM AUTHOR]

The article discusses importance of coordinated and sustained response to the threat of antibiotic resistance. Topics discussed include surveillance for hospital-acquired infections (HAIs), public health threat from multidrug-resistant gram-negative bacteria, and need to deal with Carbapenem-resistant Enterobacteriaceae (CRE) and antibiotic resistance (AR).

For 139 patients tested for Clostridium difficile infection by polymerase chain reaction, the sensitivity, specificity, positive predictive value, and negative predictive value of testing perirectal swabs vs stool specimens were 95.7%, 100%, 100%, and 99.1%, respectively. For selected patients, perirectal swabs provide an accurate toxigenic C. difficile detection strategy. [ABSTRACT FROM AUTHOR]

Background. Klebsiella pneumoniae isolates harboring the K. pneumoniae carbapenemase gene (blaKPC) are creating a significant healthcare threat in both acute and long-term care facilities (LTCFs). As part of a study conducted in 2004 to determine the risk of stool colonization with extended-spectrum cephalosporin-resistant gram-negative bacteria, 12 isolates of K. pneumoniae that exhibited nonsusceptibility to extended-spectrum cephalosporins were detected. All were gastrointestinal carriage isolates that were not associated with infection. Methods. Reassessment of the carbapenem minimum inhibitory concentrations using revised 2011 Clinical Laboratory Standards Institute breakpoints uncovered carbapenem resistance. To further investigate, a DNA microarray assay, PCR-sequencing of bla genes, immunoblotting, repetitive-sequence-based PCR (rep-PCR) and multilocus sequence typing (MLST) were performed. Results. The DNA microarray detected blaKPC in all 12 isolates, and blaKPC-3 was identified by PCR amplification and sequencing of the amplicon. In addition, a blaSHV-11 gene was detected in all isolates. Immunoblotting revealed “low-level” production of the K. pneumoniae carbapenemase, and rep-PCR indicated that all blaKPC-3-positive K. pneumoniae strains were genetically related (≥98% similar). According to MLST, all isolates belonged to sequence type 36. This sequence type has not been previously linked with blaKPC carriage. Plasmids from 3 representative isolates readily transferred the blaKPC-3 to Escherichia coli J-53 recipients. Conclusions. Our findings reveal the “silent” dissemination of blaKPC-3 as part of Tn4401b on a mobile plasmid in Northeast Ohio nearly a decade ago and establish the first report, to our knowledge, of K. pneumoniae containing blaKPC-3 in an LTCF caring for neurologically impaired children and young adults. [ABSTRACT FROM AUTHOR]

Background. Fluoroquinolones are the most commonly prescribed antimicrobials. The epidemiology of fecal colonization with Escherichia coli demonstrating reduced susceptibility to fluoroquinolones remains unclear. Methods. During a 3-year period (15 September 2004 through 19 October 2007), all patients hospitalized for 13 days were approached for fecal sampling. All E. coli isolates with reduced susceptibility to fluoroquinolones (minimum inhibitory concentration [MIC] of levofloxacin, ⩾0.125 μg/mL) were identified. We characterized gyrA and parC mutations and organic solvent tolerance. Isolates were compared using pulsed-field gel electrophoresis. Results. Of 353 patients colonized with E. coli demonstrating reduced fluoroquinolone susceptibility, 300 (85.0%) had ⩾1 gyrA mutation, 161 (45.6%) had ⩾1 parC mutation, and 171 (48.6%) demonstrated organic solvent tolerance. The mean numbers of total mutations (ie, gyrA and parC) for E. coli isolates with a levofloxacin MIC of ⩾8 μg/mL versus ⩾8.0 μg/mL were 2.70 and 0.82 (P!.001). Of the 136 E. coli isolates with a levofloxacin MIC of ⩾8 μg/mL, 90 (66.2%) demonstrated a nalidixic acid MIC of ⩾16 μg/mL. Significant differences were found over time in the proportion of E. coli isolates demonstrating gyrA mutation, parC mutation, and organic solvent tolerance. There was little evidence of clonal spread of isolates. Conclusions. Gastrointestinal tract colonization with E. coli demonstrating reduced susceptibility to levofloxacin is common. Although 40% of study isolates exhibited a levofloxacin MIC of <8 μg/mL (and would thus be missed by current Clinical and Laboratory Standards Institute breakpoints), nalidixic acid resistance may be a useful marker for detection of such isolates. Significant temporal changes occurred in the proportion of isolates exhibiting various resistance mechanisms. [ABSTRACT FROM AUTHOR]

Background. The characteristics of colonization with multidrug-resistant gram-negative bacteria (MDRGNB) in the gastrointestinal tract have not been well defined. Characterizing the duration of colonization, clearance of colonization, and frequency of cocolonization would provide important information for the development of interventions targeting the prevention of MDRGNB spread. Methods. From 31 October 2006 through 22 October 2007, serial rectal cultures were obtained every 3-4 weeks from residents of a long-term care facility. Clearance of colonization was defined as ⩾2 consecutive cultures from which MDRGNB were not recovered. Factors associated with clearance of colonization were analyzed using time-to-event methods. Results. Thirty-three patients colonized with 57 MDRGNB isolates were followed up for a median of 211 days (range, 63-356 days). Twenty (61%) of the patients were colonized with ⩾1 different MDRGNB species (median, 2 strains; range, 1-4 strains). The median duration of MDRGNB colonization was 144 days (range, 41-349 days). Clearance of colonization with all MDRGNB strains occurred in 3 patients (9%). Clearance of MDRGNB colonization, calculated by colonizing strain, occurred in 22 (39%) of 57 MDRGNB colonization episodes, with a rate of colonization clearance of 2.6 episodes per 1000 days. Clearance of multidrug-resistant Proteus mirabilis colonization occurred in 1 (6.7%) of 15 episodes, compared with clearance of 21 (50%) of 42 colonization episodes due to other MDRGNB species (hazard ratio, 0.1; 95% confidence interval, 0.01-0.78; P = .03). Conclusions. Patient colonization with MDRGNB is prolonged, and a substantial proportion of patients are colonized with multiple MDRGNB species. Multidrug-resistant P. mirabilis may have a survival advantage in the gastrointestinal tract, compared with other MDRGNB species. [ABSTRACT FROM AUTHOR]

We performed a prospective cohort study to quantify the number of cases of patient-to-patient transmission of extended-spectrum β-lactamase-producing Klebsiella species on perianal surveillance culture. Among 27 patients who acquired Klebsiella pneumoniae infection, 14 had infections (52%) that were due to patient-to-patient transmission, and 6 (22%) had a subsequent positive extended-spectrum blactamase clinical culture results. [ABSTRACT FROM AUTHOR]