Clinical impact and risk factors for colonization with extended-spectrum β-lactamase-producing bacteria in the intensive care unit

Purpose

The changed epidemiology of extended spectrum beta-lactamases (ESBL), the spread to the community and the need for prudent use of carbapenems require updated knowledge of risk factors for colonization with ESBL-producing enterobacteriaceae (ESBL-PE).

Methods

An 8-month prospective study in the medical ICU of an 850-bed general and university-affiliated hospital.

Results

Of 610 patients admitted, 531 (87?%) had a rectal swab obtained at admission, showing a 15?% (82 patients) ESBL-PE carriage rate, mostly of E. coli (n?=?51, 62?%); ESBL-PE caused 9 (3?%) infections on admission. By multivariable analysis, transfer from another ICU (OR?=?2.56 [1, 22]), hospital admission in another country [OR?=?5.28 (1.56–17.8)], surgery within the past year [OR?=?2.28 (1.34–3.86)], prior neurologic disease [OR?=?2.09 (1.1–4.0)], and prior administration of third generation cephalosporin (within 3–12?months before ICU admission) [OR?=?3.05 (1.21–7.68)] were independent predictive factors of colonization by ESBL-PE upon ICU admission. Twenty-eight patients (13?% of those staying for more than 5?days) acquired ESBL carriage in ICU, mostly with E. cloacae (n?=?13, 46?%) and K. pneumoniae (n?=?10, 36?%). In carriers, ESBL-PE caused 10 and 27?% of first and second episodes of ICU-acquired infections, respectively.

Conclusion

We found a high prevalence of ESBLE-PE colonization on admission to our ICU, even in the subgroup admitted from the community, but few first infections. Identifying risk factors for ESBL-PE colonization may help identifying which patients may warrant empiric ESBL-targeted antimicrobial drug therapy as a means to limit carbapenem use.     

Interspecies plasmid transfer appears rare in sequential infections with extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae

From a cohort of 1836 Swedish patients infected with ESBL-producing Enterobacteriaceae (EPE) during 2004–2014, 513 patients with recurrent EPE infection were identified. Only in 14 of the 513 patients was a change of species (ESBL-E. coli to ESBL-K. pneumoniae or vice versa) found between the index and subsequent infection. Eleven sequential urine isolates from 5 of the 14 patients were available for further analysis of possible transfer of ESBL-carrying plasmids. The plasmid content was studied using optical DNA mapping (ODM), PCR-based replicon typing, and ESBL gene sequencing. ODM allowed us to directly compare whole plasmids between isolates and found similar ESBL-carrying plasmids in 3 out of the 5 patients. The ODM results and the rarity in shift of species between ESBL-E. coli and ESBL-K. pneumoniae imply that in recurrent EPE infections interspecies plasmid transfer is uncommon.     

Clinical characteristics and outcome of critically ill patients with bacteremia caused by extended-spectrum β-lactamase-producing and non-producing Escherichia coli

The number of patients infected with extended-spectrum beta-lactamase (ESBL)-producing organisms has increased dramatically worldwide, and high mortality rates are seen in severely ill patients. This study retrospectively compared the clinical characteristics and outcomes of critically ill patients in an intensive care unit (ICU) at the Tsuyama Chuo Hospital (Okayama, Japan) who were hospitalized for bacteremia caused by ESBL-producing Escherichia coli (ESBL-EC) or non-ESBL-producing E. coli (non-ESBL-EC) between January 2006 and December 2016 (11 years). We analyzed the patients' age, sex, underlying disease(s), sequential organ failure assessment scores, primary focus of bacteremia, empiric antibiotics, rate of appropriateness of empiric antibiotics, and treatment duration, with 28-day mortality being the primary outcome. The study included 24 patients with ESBL-EC bacteremia and 77 with non-ESBL-EC bacteremia. The rate of appropriate initial antibiotic treatment was significantly lower (54.2% vs. 96.1%, respectively; P < 0.01) and the mortality due to bacteremia significantly higher (37.5% vs. 15.6%, respectively; P = 0.04) in the ESBL-EC than in the non-ESBL-EC bacteremia group. A subgroup analysis focusing on patients who were administered appropriate empiric antibiotics showed that the 28-day mortality rate did not differ significantly between the two groups (P = 0.23). To our knowledge, this is the first study to compare the outcomes of patients with ESBL-EC and non-ESBL-EC bacteremia in a Japanese ICU setting. Initial empiric antibiotic therapy covering ESBL-producing pathogens should be considered for critically ill patients in the ICU.     

Acquisition of extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae in intensive care units in Thailand

This study aimed to assess the prevalence and associated risk factors for extended-spectrum β-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae (ESBL-EK) acquisition among patients staying in medical and surgical Intensive Care Units (ICU) in Northern Thailand. Rectal swabs were collected from 206 ICU patients upon admission and discharge. Overall, the ESBL-EK acquisition rate among patients during ICU stay was 29.6%. Acquisition rate was significantly higher for K. pneumoniae (20.9%) than that of E. coli (12.1%) (p = 0.024). Multivariate logistic regression analysis identified the use of third generation cephalosporin (p = 0.008) as a risk factor for ESBL-EK acquisition. Sixty-eight ESBL-EK isolates (25 E. coli and 43 K. pneumoniae) were recovered. The majority of ESBL-EK isolates (≥88%) were resistant to ceftazidime, cefepime and aztreonam. Fifty-two acquired ESBL-EK isolates (76.5%) were positive for bla_CTX-M and 4 K. pneumoniae isolates simultaneously carried bla_NDM-1. Our results reveal that ICU patients could acquire ESBL-EK during hospitalization and the use of third generation cephalosporin should be strictly controlled to prevent the acquisition of ESBL-EK among ICU patients.     

In vitro activity of tigecycline against extended-spectrum β-lactamase-producing Enterobacteriaceae and MRSA clinical isolates from Mexico: a multicentric study

Extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae and methicillin resistant Staphylococcus aureus (MRSA) are important nosocomial pathogens. This study reports the in vitro activity of tigecycline against 573 and 482 ESBL-producing Enterobacteriaceae and MRSA isolates, respectively. More than 94% of all tested isolates were susceptible to tigecycline; MIC(90) found was 0.25 to 2 mg/L for ESBL-producing Enterobacteriaceae and was 0.125 mg/L for MRSA. Tigecycline demonstrated excellent in vitro activity against a wide spectrum of nosocomial pathogens.     

High prevalence of extended-spectrum β-lactamases and plasmid-mediated AmpC β-lactamases in Enterobacteriaceae isolated from long-term care facilities in Korea

The aim of this study was to investigate for the first time the prevalence and types of extended-spectrum β-lactamase (ESBL) and plasmid-mediated AmpC β-lactamase (PABL) in Enterobacteriaceae in Korean long-term care facilities (LTCFs). ESBL rates were 45.3% (72/159) in Escherichia coli and 42.7% (50/117) in Klebsiella pneumoniae. In E. coli, CTX-M-28, the most prevalent ESBLs, was identified for the first time in Korea in 44 isolates. In K. pneumoniae, SHV-12 was found in 27 isolates (52.9% of ESBLs), among which 25 isolates also contained SHV-11. Twenty-seven isolates had SHV and CTX-M β-lactamase simultaneously. PABL genes were detected in 39.3% (46/117) of K. pneumoniae and 3.1% (5/159) E. coli. In E. coli, DHA-1(3), CMY-2(1), and CMY-6(1) were detected, whereas in K. pneumoniae, only DHA-1 was detected. Among the PABL-producing organisms, 80.0% (E. coli) and 52.2% (K. pneumoniae) simultaneously produced ESBLs. In conclusion, LTCF residents in Korea have a very high prevalence of E. coli and K. pneumoniae producing ESBLs, PABLs, or both, and the genotypes of ESBL and PABL were identical with those found in general hospitals.     

Characteristics of infections caused by extended-spectrum β-lactamase-producing Escherichia coli from community hospitals in South Africa

A study was designed to characterize 22 nonrepeat extended-spectrum β-lactamase (ESBL)-producing Escherichia coli clinical isolates recovered from specimens originating from doctor's consultation rooms and several private and a state hospital in the Cape Town metropolitan area during 2008-2009. Characterization was done by using isoelectric focusing, PCR, sequencing of bla(CTX-M), bla(TEM), bla(SHV), and bla(OXA) as well as PCR for plasmid-mediated quinolone resistance determinants, ST131, phylogenetic groups, and plasmid replicon typing. Genetic relatedness was determined with pulsed-field gel electrophoresis using XbaI and multilocus sequencing typing. The majority of patients (17/22 [77%]) presented with urinary tract infections (UTIs) originating from the hospital setting. Thirteen (59%) of the isolates produced CTX-M-15, 7 produced CTX-M-14, and 1 isolate each produced CTX-M-3 and SHV-2, respectively. Sixteen (73%) isolates were nonsusceptible to ciprofloxacin and 8 (36%) were positive for aac(6')-Ib-cr. Overall, 10/22 (45%) of ESBL producers belonged to clonal complex ST131 that produced CTX-M-15 or CTX-M-14. Molecular characteristics of ST131 showed that this clone belonged to phylogenetic group B2. Our study illustrated that clonal complex ST131 isolates producing CTX-M-15 and CTX-M-14 had emerged as an important cause of UTIs due to ESBL-producing E. coli in the Cape Town area. This is the first report to identify ST131 in ESBL-producing E. coli from Southern Africa.     

Salvage therapy with tigecycline for recurrent infection caused by ertapenem-resistant extended-spectrum β-lactamase-producing Klebsiella pneumoniae

Optimal antimicrobial therapy for infections due to ertapenem-resistant Enterobacteriaceae remains undetermined. In this study, a diabetic patient with recurrent pyomyositis and osteomyelitis caused by extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae developed ertapenem resistance after imipenem/cilastatin treatment, which was a currently recommended therapy. He was finally treated successfully using tigecycline. Ertapenem resistance was in part explained by the production of SHV-type ESBL and the absence of an outer membrane protein, OmpK36. Our observation suggests that tigecycline may be an alternative for invasive infections caused by ESBL-producing Enterobacteriaceae with decreased susceptibility to carbapenem.     

Prevalence of fecal carriage of extended-spectrum β-lactamase-producing Enterobacteriaceae among healthy adult people in Japan

In Japan, the prevalence of extended-spectrum β-lactamase (ESBL) producers in hospital settings has shown an increasing trend. In the present study, we investigated the prevalence of the fecal carriage of ESBL-producing Enterobacteriaceae among healthy adults. Stool samples were collected for the phenotypic and genotypic identification of ESBL-producing Enterobacteriaceae. We found the prevalence of ESBL producers to be 6.4% by phenotypic identification, and 92.9% of them possessed the bla _CTX-M gene. Among the CTX-M ESBL-producing Enterobacteriaceae, we identified 11 Escherichia coli and 2 Klebsiella pneumonia strains. The findings suggest that the fecal carriage of CTX-M-type ESBL producers by healthy people is rapidly increasing in Japan. This may be one of the causes of the increased spread of ESBL-producing bacteria in hospitals.