Dissemination of extended-spectrum beta-lactamase-producing Enterobacteriaceae in pediatric intensive care units

To study the growing trend of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae in pediatric intensive care units (PICUs), 88 nonrepetitive ESBL-producing isolates were prospectively collected and analyzed by molecular methods during a 16-month period. The emergence and dissemination of ESBL-producing Enterobacteriaceae in PICUs are the consequence of the clonal dissemination of a few epidemic strains along with the horizontal transmission of resistance gene-carrying plasmids among bacterial organisms.     

Nationwide surveillance of antimicrobial resistance among Enterobacteriaceae in intensive care units in Taiwan

To determine the antimicrobial resistance profiles among clinical isolates of Enterobacteriaceae in Taiwanese intensive care units (ICUs), a national surveillance of antibiotic resistance among important Enterobacteriaceae was conducted from September 2005 through November 2005 at the ICUs of ten major teaching hospitals in Taiwan. A total of 574 Enterobacteriaceae isolates recovered from various clinical samples of our ICU patients were submitted for in vitro test. Minimum inhibitory concentrations (MICs) of these isolates to 18 antimicrobial agents were determined by the broth microdilution method. The prevalences of Enterobacteriaceae isolates with phenotypic extended-spectrum β-lactamase (ESBL) production were 26% in Klebsiella pneumoniae, 16% in Serratia marcescens, 14% in Escherichia coli, and 13% in Proteus mirabilis, in which a significantly rising prevalence of ESBL production among K. pneumoniae was noted (p = 0.002) when compared with a previous Taiwanese survey in 2000. Heterogeneous resistance to various fluoroquinolones was found among our Enterobacteriaceae isolates, except for Entetrobacter cloacae. Emergence of ertapenem-resistant isolates of E. coli, K. pneumoniae, E. cloacae, and S. marcescens was noted. Gradually increasing rates of drug-resistant Enterobacteriaceae were noted in Taiwanese ICUs. Periodic surveillance of the evolutionary trend of antimicrobial resistance among ICU isolates is crucial for starting appropriately empirical antimicrobial therapy in the future.     

In vitro activity of temocillin against prevalent extended-spectrum beta-lactamases producing Enterobacteriaceae from Belgian intensive care units

Temocillin is a narrow spectrum penicillin with high stability to most β-lactamases including AmpC types and extended-spectrum types (ESBLs). We have analysed its in vitro activity against 652 clinical isolates of Enterobacteriaceae prospectively collected from patients hospitalised in intensive care units at seven different university hospitals in Belgium in 2005. Strains were screened for ESBL production using cefotaxime and ceftazidime screen agar plates and by double ESBL E-tests. The MIC of temocillin and of five comparators was determined using the E-test method. ESBLs were characterized at one central laboratory by isoelectric focusing, PCR for bla genes of the SHV, TEM, and CTX-M families, and by DNA sequencing. The prevalence of ESBL-producing Enterobacteriaceae averaged 11.8% and ranged between 3.0 and 29% in the different hospitals. Meropenem exhibited the highest in vitro activity overall (mode MIC 0.064 μg; MIC₉₀; 0.19 μg/ml), whereas ceftazidime (MIC₉₀ > 256 μg/ml) and ciprofloxacin (MIC₉₀ > 32 μg/ml) scored the worst. Temocillin was active against more than 90% of the isolates including most AmpC- and ESBL-producing isolates. These data indicate the well preserved activity of temocillin over the years against Enterobacteriaceae and show the wide variation in prevalence of ESBL-producing Enterobacteriaceae isolates in Belgian intensive care units. Prospective clinical studies are, however, needed to validate the usefulness of temocillin in the treatment of microbiologically documented infections caused by ESBL- and/or AmpC- overproducing nosocomial Enterobacteriaceae pathogens.     

Clinical implications and risk factors of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae infection in children: a case-control retrospective study in a medical center in southern Taiwan.

BACKGROUND AND PURPOSE: Infections caused by extended-spectrum beta-lactamase (ESBL)-producing Gram-negative bacilli constitute a growing problem worldwide. However, studies focusing on children are limited. METHODS: We have observed an increase in cases of ESBL-producing Klebsiella pneumoniae (ESBL-KP) infections in the past 6 years in our hospital in southern Taiwan. Using a case-control study design, we compared the clinical characteristics between 54 patients infected by ESBL-KP and 54 frequency-matched controls infected by non-ESBL-producing isolates. RESULTS: Risk factors associated with the infection of ESBL-KP were mainly longer pre-infection hospital stay and recent antibiotic exposure (within 30 days before the episode). Other potential risk factors included recent surgery, the application of mechanical ventilation, nasogastric tubes and central venous catheter insertion. ESBL-KP-related infection cases had a longer hospital stay than controls, and also had a higher mortality rate, although not significantly so. CONCLUSIONS: Recent antibiotic exposure was by far the most important predisposing factor associated with infection of ESBL-KP. Unnecessary antibiotic use should be avoided both in the hospital and community, especially ceftazidime, vancomycin/teicoplanin, aminoglycosides and ampicillin. In our study, carbapenem antibiotics remained the most active drugs against ESBL-KP in pediatric patients, while flomoxef and ciprofloxacin were suitable alternative choices.     

Evaluation of a new selective chromogenic agar medium for detection of extended-spectrum beta-lactamase-producing Enterobacteriaceae

A novel chromogenic agar medium (ESBL-Bx; bioMérieux, Marcy l'Etoile, France) was compared to MacConkey agar supplemented with 2 mg ceftazidime/liter (MCKC) for the selective isolation and presumptive identification of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae directly from clinical samples. Of a total of 644 clinical specimens (including 551 fecal samples), 496 yielded no growth and 148 yielded growth on one or both media. Overall, 44 ESBL-producing Enterobacteriaceae strains (Escherichia coli [n=17], Enterobacter aerogenes [n=17], Klebsiella spp. [n=5], and Citrobacter freundii [n=5]) were isolated from 37 specimens by a combination of both methods after 18 to 24 h of incubation. The sensitivities were 97.7 and 84.1% for ESBL-Bx and MCKC, respectively, with 43 ESBL-positive strains isolated as colored colonies from 36 specimens on ESBL-Bx versus 37 ESBL-positive organisms isolated from 32 specimens on MCKC. The specificities by specimens were 89 and 91% for ESBL-Bx and MCKC, respectively. On either one of the two media, natural AmpC-hyperproducing Enterobacter spp. (n=25) and Citrobacter spp. (n=14) were the most common false positives as well as non-ESBL-producing Klebsiella oxytoca (n=18) on ESBL-Bx and Morganella morganii (n=10) on MCKC. We conclude that ESBL-Bx is a sensitive and specific medium for the isolation of ESBL-producing Enterobacteriaceae from clinical samples. The main advantages of ESBL-Bx over MCKC reside in its chromogenic character and its sensitivity and selectivity, which enabled the recovery and presumptive identification of most ESBL-producing Enterobacteriaceae within 24 h and reduced by 27% the need for unnecessary identification and confirmation of ESBL testing when disregarding all colorless colonies growing on this medium.     

Bacteremia due to extended-spectrum beta-lactamase-producing Enterobacteriaceae other than Escherichia coli and Klebsiella.

BACKGROUND AND PURPOSE: Carbapenems are considered the drugs of choice for the treatment of serious infections caused by extended-spectrum beta-lactamase (ESBL)-producing Klebsiella and Escherichia coli. However, controversy exists about the antibiotic choice for infections due to ESBL-producing organisms of other genera. METHODS: This retrospective study evaluated the risk factors and outcomes of 54 adult patients with bacteremia due to ESBL-producing Enterobacteriaceae other than Klebsiella spp. or E. coli treated at a tertiary care hospital in northern Taiwan from January 2001-December 2003. Patients were categorized into carbapenem (n = 22) and non-carbapenem (n = 32) treatment groups. All patients had at least one positive blood culture together with fever or other clinical features compatible with systemic infection. RESULTS: Higher Acute Physiology and Chronic Health Evaluation II score, glucocorticoid use, and presentation of septic shock were significant risk factors for mortality (p<0.05). Patients treated with a carbapenem had a better 14-day or overall survival rate (i.e., survived to discharge) than those treated with non-carbapenem antibiotics, although this difference was not significant. Among patients in the non-carbapenem group, the overall survival rates of ciprofloxacin, aminoglycoside, and ceftazidime were 70% (14/20), 62.5% (5/8), and 50% (2/4), respectively (p=0.877). The overall survival rates of the carbapenem (72.7%) and ciprofloxacin (70.0%) groups were similar. CONCLUSIONS: The results suggest that ciprofloxacin, when indicated based on antimicrobial susceptibility testing, may serve as an alternative choice for infections caused by ESBL-producing Enterobacteriaceae other than E. coli or Klebsiella spp. and may not affect the clinical outcome at discharge.     

Molecular epidemiology of extended-spectrum beta-lactamase-producing,fluoroquinolone-resistant isolates of Klebsiella pneumoniae in Taiwan

Strains of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBL-KP) have emerged worldwide. Concomitant ciprofloxacin resistance with ESBL production in K. pneumoniae isolates would severely restrict treatment options. Among 39 (18.5%) of 211 ESBL-KP isolates resistant to ciprofloxacin (MIC, >/=4 micro g/ml), 37 (95%) were high level resistant (MIC, >/=16 micro g/ml). These isolates were also cross resistant to the newer fluoroquinolones, including levofloxacin, gatifloxacin, gemifloxacin, and garenoxacin (BMS 284756). Sitafloxacin was most active against these ciprofloxacin-resistant ESBL-KP isolates with MICs for 67% of the isolates being 相似文献   

Endemic extended-spectrum beta-lactamase-producing Klebsiella pneumoniae at an intensive care unit: risk factors for colonization and infection

A prospective cohort study was undertaken to describe the epidemiology of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBLKp) acquisition at an intensive care unit (ICU) in a non-outbreak setting. Surveillance for ESBLKp colonization and infection was performed in patients admitted at the ICU from January, 2000, to May, 2001. Screening for ESBLKp intestinal colonization was done by culturing rectal swab specimens at admission, 72 hr after admission and weekly until discharge or detection of ESBLKp. The incidence of ESBLKp intestinal colonization was 5.8/1,000 patient-days (95%CI, 3.4-10.1), and of ESBLKp infection was 1.7/1,000 patient-days (95%CI, 0.7-4.2). Use of vancomycin (OR 6.6; 95%CI, 1.73-25.28), amphotericin B (OR 12.0; 95%CI, 1.79-80.51), metronidazole (OR 5.3; 95%CI, 1.10-25.65), and ciprofloxacin (OR 0.1; 95%CI, 0.01-0.97) were independently associated with ESBLKp intestinal colonization. Previous ESBLKp colonization (OR 60.6; 95%CI, 56.33-578.73) was independently associated with ESBLKp infection. Each ICU-acquired ESBLKp isolate belonged to a different genotype by ERIC-PCR or pulsed-field gel electrophoresis (PFGE) and had a different plasmid profile, suggesting that cross transmission was not the main source for ESBLKp acquisition. Factors associated with ESBLKp in the non-outbreak setting were different from those previously reported during outbreaks. Intestinal ESBLKp colonization was confirmed as a risk factor for infection by this pathogen.     

Dramatic increase in prevalence of fecal carriage of extended-spectrum beta-lactamase-producing Enterobacteriaceae during nonoutbreak situations in Spain

The occurrence of extended-spectrum beta-lactamase (ESBL)-producing isolates has increased worldwide. Fecal carriage of ESBL-producing isolates has mainly been detected in nosocomial outbreaks, and few studies have evaluated fecal carriage during nonoutbreak situations and among patients in the community. We have studied the prevalence of ESBLs in 1,239 fecal samples from 849 patients (64.1% of whom were ambulatory) in 1991 and have compared the prevalence data with those obtained in 2003 for 400 fecal samples from 386 patients (75.9% of whom were ambulatory) and 108 samples from independent healthy volunteers. Samples were diluted in saline and cultured in two MacConkey agar plates supplemented with ceftazidime (1 microg/ml) and cefotaxime (1 microg/ml), respectively. Colonies were screened (by the double-disk synergy test) for ESBL production. The clonal relatedness of all ESBL-producing isolates was determined by pulsed-field gel electrophoresis with XbaI digestion; and the ESBLs of all ESBL-producing isolates were characterized by isoelectric focusing, PCR, and sequencing. The rates of fecal carriage of ESBL-producing isolates increased significantly (P < 0.001) in both hospitalized patients and outpatients, from 0.3 and 0.7%, respectively, in 1991, to 11.8 and 5.5%, respectively, in 2003. The rate of occurrence of ESBL-producing isolates among healthy volunteers was 3.7%. All ESBL-producing isolates recovered in 2003 were nonepidemic clones of Escherichia coli. ESBL characterization revealed an increasing diversity of ESBL types: TEM-4 and CTX-M-10 were the only enzymes detected in 1991, whereas TEM-4, TEM-52, SHV-12, CTX-M-9, CTX-M-10, CTX-M-14, and a CTX-M-2-like enzyme were recovered in 2003. The ESBL-producing isolates recovered from outpatients in 2003 corresponded to a CTX-M-9-type cluster (62.5%) and SHV-12 (31.2%), whereas TEM-4 was detected only in hospitalized patients. The frequencies of coresistance in isolates recovered in 2003 were as follows: sulfonamide, 75%; tetracycline, 64.3%; streptomycin, 57.1%; quinolones, 53.5%; and trimethoprim, 50%. The increased prevalence of fecal carriage of ESBL-producing isolates during nonoutbreak situations in hospitalized patients and the establishment of these isolates in the community with coresistance to non-beta-lactam antibiotics, including quinolones, represent an opportunity for these isolates to become endemic.     

Genetic relatedness among extended-spectrum beta-lactamase-producing Klebsiella pneumoniae outbreak isolates associated with colonization and invasive disease in a neonatal intensive care unit

Pulsed-field gel electrophoresis typing of 60 extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBLKp) isolates obtained in a neonatal intensive care unit during an outbreak indicated the dissemination of two major bacterial genotypes associated with colonization and invasive disease: one composed by aminoglycoside-resistant isolates and the other by aminoglycoside-susceptible isolates. A urease-negative phenotype was observed among aminoglycoside-resistant ESBLKp. Six pairs of isolates from gastrointestinal (GI) colonization and isolates from invasive disease that occurred 3-23 days later were shown to belong to the same genotype, reinforcing a direct association between colonization and subsequent disease. These data indicate that screening for ESBLKp GI colonization in an outbreak setting may be useful to detect neonates at a higher risk of invasive disease.     

Current options for the treatment of infections due to extended-spectrum beta-lactamase-producing Enterobacteriaceae in different groups of patients

BackgroundExtended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) are a frequent cause of invasive infections worldwide. Carbapenems are nowadays the most used drugs to treat these infections. However, due to the increasing rates of resistance to these antimicrobials, carbapenem-sparing alternatives are being investigated.Objectives and sourcesThe aim of this narrative literature review is to summarize the published information on the currently available antibiotics for the treatment of ESBL-E infections, providing specific information on three subgroups of patients: Group 1, patients with severe infections or infections from high-risk sources or in severely immunocompromised patients; Group 2, patients with non-severe infections from intermediate-risk source; and Group 3, patients with non-severe urinary tract infection.Content and implicationsFor patients in Group 1, the current data would support the use of carbapenems. For milder infections, however, particularly urinary tract infections, other non-carbapenem antibiotics can be considered in selected cases, including beta-lactam/beta-lactam inhibitor combinations, cephamycins, temocillin and aminoglycosides. While specific studies should be performed in these situations, individualized decisions may be taken in order to avoid overuse of carbapenems.     

National bundle care program implementation to reduce ventilator-associated pneumonia in intensive care units in Taiwan

Background/purposeThis study investigated the impact of implementing ventilator-associated pneumonia (VAP) bundle care on the rates of VAP in intensive care units (ICUs) in Taiwan.MethodsA total of 10 ICUs (bed number, 170), including surgical (SICUs) (n = 7), cardiovascular/surgical (CV/S-ICUs) (n = 1), and medical ICUs (MICUs) (n = 2) from 10 hospitals (7 medical center hospitals and 3 regional hospitals) were enrolled in this quality-improvement project. This study was divided into the pre-intervention phase (1st January, 2012–31st July, 2013) and the intervention phase (1st August, 2013–31st October, 2014).ResultsAmong the 10 hospitals, the overall rates (cases per 1000 ventilator-days) of VAP declined significantly (p = 0.005; rate ratio, 0.71) from 1.9 in the pre-intervention period to 1.5 in the intervention period. Significant difference in VAP rates between these periods was found in the regional hospitals (from 1.6 to 0.7; p < 0.001) and the SICUs (from 2.1 to 1.4; p < 0.001), but not in the medical centers (2.0 vs. 1.9; p = 0.0667) or CV/S-ICUs (4.5 vs. 4.5; p = 0.5391). However, VAP rate increased significantly (cases per 1000 ventilator-days) in the MICUs between the two periods (from 0.5 to 1.0; p = 0.0489). For the VAP bundle care elements, the overall compliance rate was 87.7% with 83.6% and 97.9% in the medical centers and regional hospitals, respectively.ConclusionsImplementing VAP bundle care has effectively reduced VAP in Taiwanese ICUs, but differences in performance and compliance rates of VAP bundle care among the different ICUs and hospital categories did exist.     

Implementation of a national bundle care program to reduce central line-associated bloodstream infections in intensive care units in Taiwan

Background/purpose

This study assessed the effect of the central line bundle on the rate of central line-associated bloodstream infections (CLABSI) in intensive care units (ICUs) in Taiwan.

Extended-spectrum beta-lactamase-producing Enterobacteriaceae in Bulgarian hospitals

The aim of the study was to describe the emergence, the spread, and the prevalence of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae in Bulgaria. Over eight years (1996-2003), 442 ESBL-screen-positive isolates were collected in nine medical institutions in four Bulgarian towns. Class A ESBLs of the SHV, TEM, and CTX-M groups were identified in seven species. SHV-type enzymes persisted during the whole study period, TEM-ESBLs appeared first in 1999, and CTX-M-types appeared first in 2001. The rate of CTX-M enzyme producers increased rapidly between 2001 and 2003, while the rate of SHV producers decreased. Six different ESBL-types were identified, namely, SHV-2, -5, and -12, CTX-M-3 and -15, and a new TEM-3-like variant (TEM-139). The most widespread enzymes were SHV-12, CTX-M-15, and CTX-M-3 found in seven centers. TEM-139 was identified mainly in one center. A trend for strains harboring more than one ESBL gene, for example, CTX-M + SHV, was observed since 2002. Plasmid fingerprinting and random amplified polymorphic DNA analysis typing revealed wide dissemination of identical plasmids among different bacterial species and hospitals, as well as clonal spread of ESBL producers. Our data contribute to clarify the dynamics in the prevalence of ESBLs in Bulgaria and demonstrate the importance of molecular procedures for their analysis.     

Occurrence and detection of extended-spectrum beta-lactamases in members of the family Enterobacteriaceae at a veterans medical center: seek and you may find.

A total of 907 consecutive isolates of members of the family Enterobacteriaceae recovered during a 20-week period were tested for production of extended-spectrum beta-lactamases (ESBLs) by the double-disk (DD) potentiation method. Of 84 DD-positive isolates, 83 (9.2%) produced ESBLs based on isoelectric focusing. SHV-derived ESBLs and several TEM-derived ESBLs were present in nine species, including the first isolate of Citrobacter koserii and Morganella morganii known to harbor an SHV-derived ESBL. Results of testing 58 nonrepeat isolates for ESBL production by several recommended methods were as follows (percent detected in parentheses): DD method with aztreonam (95), ceftazidime (79), ceftriaxone (88), or cefpodoxime (90); broth microdilution method with ceftazidime (86) or cefotaxime (91) alone or in combination with clavulanate; and the standard disk diffusion method with new breakpoints and standard concentrations of aztreonam (78), ceftazidime (79), ceftriaxone (83), or cefpodoxime (98) or a novel concentration (5 microg) of ceftazidime (88). In three instances during an extended part of the study, an ESBL-producing isolate and a non-ESBL-producing isolate of the same species were recovered from a single blood culture bottle. These data indicate that ESBLs occur in several species of Enterobacteriaceae and at a relatively high incidence at our institution and that the standard disk diffusion method with cefpodoxime and the DD method with several beta-lactams are practical and cost-effective methods for detecting ESBL-producing isolates of Enterobacteriaceae.     

Detection and clinical significance of extended-spectrum beta-lactamases in a tertiary-care medical center.

The prevalence of extended-spectrum beta-lactamase (ESBL)-mediated resistance remains unknown for most hospitals, and national guidelines for testing and reporting ESBL-mediated resistance have not yet been developed. We undertook a study to determine the prevalence of ESBLs and the clinical need for testing in our tertiary-care medical center. Members of the family Enterobacteriaceae isolated over a 6-month period for which ceftazidime or ceftriaxone MICs were greater than 1 microg/ml were tested for production of ESBLs by the double-disk synergy method. Approximately 1.5% of isolates of the family Enterobacteriaceae (50 of 3,273), which were isolated from 1.2% of patients (23 of 1,844), were found to express ESBLs. ESBL-producing strains included eight different species and were isolated from patients located throughout the hospital, including outpatient clinics. By using the interpretive guidelines of the National Committee for Clinical Laboratory Standards, 26 to 39% of the isolates would have been reported to be susceptible to ceftazidime, depending upon the routine susceptibility method used. However, tests with cefpodoxime found all of the ESBL-producing strains to be resistant or intermediate. Nine patients infected with ESBL-producing isolates were treated with therapy which included an expanded-spectrum cephalosporin. Seven were cured. The deaths of the other two patients were not attributed to bacterial resistance missed by routine susceptibility testing. These observations suggest that in our tertiary-care medical center, it may not be clinically necessary or cost-effective at this time to institute additional testing on a routine basis to detect ESBL production in all clinical isolates of the family Enterobacteriaceae.