Antibiograms of multidrug-resistant clinical Acinetobacter baumannii: promising therapeutic options for treatment of infection with colistin-resistant strains.

Multidrug-resistant Acinetobacter baumannii infection has presented a global medical challenge. The antibiograms of paired colistin-susceptible and -resistant strains revealed increased susceptibility of colistin-resistant strains to most tested antibiotics, including those that are active against only gram-positive bacteria. Synergy between colistin and rifampicin was observed in the colistin-susceptible strains. The ability to form biofilm in the colistin-resistant strains was significantly lower (P<.001) than in the parent strains. Our study provides valuable information for potential expansion of our current therapeutic options against colistin-resistant A. baumannii infection.

Prevalence of antimicrobial resistances in common pathogenic Enterobacteriaceae in Australia, 2004: report from the Australian Group on Antimicrobial Resistance.

Antibiotic resistance in 3 common pathogenic types of Enterobacteriaceae was examined in a pointprevalence study in 2004. Strains of Escherichia coli, Klebsiello and Enterobacter species were collected prospectively in 25 institutions in Australian capital cities and tested by broth microdilution to 12 13-lactams and 3 other antibiotics. Almost 22% of isolates tested were from blood cultures. In E. coli, acquired resistance to ampicillin and piperacillin was common (> 40%), and clinically significant percentages of intermediate susceptibility and resistance (> 8%) were observed to amoxycillin-clavulanate, cefazolin and trimethoprim. In Klebsiella species, clinically important acquired resistance (> 8%) was seen to piperacillin, cephalothin and trimethoprim, while in Enterobacter species, this was found with piperacillin, ceftriaxone, ceftazidime and trimethoprim. Blood culture isolates had similar rates of resistance to isolates from other specimen sources. New South Wales/Australian Capital Territory (combined) tended to have higher percentages of resistance than the other states, which were otherwise comparable across the agents and species tested. Multi-resistance, defined as more than 3 acquired resistances to antibiotic classes, was found in 6.5% of E. coli, 8.3% in Klebsiella species and 16.9% of Enterobacter species. Co-resistance to ciprofloxacin, gentamicin and/or trimethoprim was common in isolates presumptively harbouring extended-spectrum beta-lactamases. Strains with extended-spectrum beta-lactamases, although common in other countries, appear to be at fairly low levels in Australia; less than 4% in E. coli and less than 9% in Klebsiella species. Rates in Enterobacter species were not able to be determined. Presumptive plasmid-borne AmpC beta-lactamases were seen at low levels across the country and carbapenemases have now been found for the first time in Australia in Enterobacteriaceae. Both of these types of resistance represent a significant threat to major last-line antibiotics.

Large outbreak of infection and colonization with gram-negative pathogens carrying the metallo- beta -lactamase gene blaIMP-4 at a 320-bed tertiary hospital in Australia.

A large outbreak of infection and colonization with multiple genera of gram-negative bacilli carrying the metallo- beta -lactamase gene bla(IMP-4) occurred in a 36-bed intensive care unit at a tertiary hospital in Australia. The organisms emerged rapidly, caused severe infections, and contributed to mortality. Controlling the spread of these organisms remains a challenge for all staff involved.

Phenotypic detection of carbapenem-susceptible metallo-beta-lactamase-producing gram-negative bacilli in the clinical laboratory.

Rapid detection of metallo-beta-lactamase (MBL)-producing gram-negative pathogens is critical to prevent their widespread dissemination. Thus far, no standardized phenotypic method is available, and previously reported techniques have poor sensitivity for detecting carbapenem-susceptible MBL-carrying isolates, an increasingly described phenomenon. We developed a phenotypic detection method using both a double-disk synergy test and a combined-disk test with imipenem and 292 microg EDTA on one agar plate. Genotypic confirmation was used for validation. Of the 134 clinical isolates, 84 were confirmed to carry an MBL. Of these, 51 (61%) were susceptible to at least one carbapenem, and 22 (26%) were isolated from blood. The phenotypic method correctly differentiated all MBL-producing isolates (sensitivity, 100%). Fifty-one of the 52 MBL-negative isolates were correctly differentiated (specificity, 98%). This study reports the validation of a simple and accurate MBL detection method that can be easily incorporated into the daily routine of a clinical laboratory. Early detection of MBL-carrying organisms, including those with susceptibility to carbapenems, is of paramount clinical importance, as it allows rapid initiation of strict infection control practices as well as therapeutic guidance for confirmed infection.

Emergence of carbapenem resistance in Acinetobacter baumannii recovered from blood cultures in Australia.

We describe the first emergence of carbapenem-resistant Acinetobacter baumannii in Australia. Ninety A. baumannii isolates recovered from cultures of blood specimens from 69 patients were analyzed. Overall, 58 isolates (64%) were resistant to meropenem. The chi 2 test for linear trend revealed that emergence of carbapenem resistance was statistically significant during the 32-month study period. Selected isolates were of the same clonal type, and no genes encoding carbapenemases were identified.

Dissemination of the metallo-beta-lactamase gene blaIMP-4 among gram-negative pathogens in a clinical setting in Australia.

BACKGROUND: The clinical utility of carbapenems is under threat because of the emergence of acquired metallo-beta-lactamase (MBL) genes. We describe the first outbreak in Australia of infection and/or colonization with gram-negative pathogens carrying the MBL gene blaIMP-4. METHODS: MBL-producing organisms were identified using susceptibility data in conjunction with MBL screening methods. PCR and sequence analysis were performed to characterize the resistance gene and identify the presence of integrons. DNA profiles were determined by ribotyping. Clinical and epidemiological data were prospectively collected from January-July 2004. RESULTS: A total of 19 isolates were recovered from 16 patients: Serratia marcescens (10 isolates), Klebsiella pneumoniae (4 isolates), Pseudomonas aeruginosa (3 isolates), Escherichia coli (1 isolate), and Enterobacter cloacae (1 isolate). Isolates were resistant to most beta-lactams except aztreonam, and variable resistance to carbapenems was observed (MIC range, 2 to >8 mg/L). PCR and sequence analysis identified the blaIMP-4 gene and a class 1 integrase (IntI1) in all isolates. Of the 16 patients, 12 (75%) had infection; 5 had septicemia, 5 had ventilator-associated pneumonia, 1 had a urinary tract infection, and 1 had a superficial central venous line infection. Six (38%) of the 16 patients died, and 5 of those 6 (31% of the group of 16) had clinical infection with an MBL-producing organism. All except 2 patients had spatio-temporal epidemiological links in the intensive care unit. All K. pneumoniae isolates were of different ribogroups, whereas the S. marcescens and P. aeruginosa isolates were predominately of the same ribogroup. CONCLUSIONS: MBL-producing gram-negative organisms have now emerged in Australia. The resistance gene, blaIMP-4, appears highly mobile; this outbreak involved 5 different gram-negative genera from patients with close epidemiological links.

Risk factors for new detection of vancomycin-resistant enterococci in acute-care hospitals that employ strict infection control procedures.

Accurate assessment of the risk factors for colonization with vancomycin-resistant enterococci (VRE) among high-risk patients is often confounded by nosocomial VRE transmission. We undertook a 15-month prospective cohort study of adults admitted to high-risk units (hematology, renal, transplant, and intensive care) in three teaching hospitals that used identical strict infection control and isolation procedures for VRE to minimize nosocomial spread. Rectal swab specimens for culture were regularly obtained, and the results were compared with patient demographic factors and antibiotic exposure data. Compliance with screening was defined as "optimal" (100% compliance) or "acceptable" (minor protocol violations were allowed, but a negative rectal swab specimen culture was required within 1 week of becoming colonized with VRE). Colonization with VRE was detected in 1.56% (66 of 4,215) of admissions (0.45% at admission and 0.83% after admission; the acquisition time was uncertain for 0.28%), representing 1.91% of patients. No patients developed infection with VRE. The subsequent rate of new acquisition of VRE was 1.4/1,000 patient days. Renal units had the highest rate (3.23/1,000 patient days; 95% confidence interval [CI], 1.54 to 6.77/1,000 patient days). vanB Enterococcus faecium was the most common species (71%), but other species included vanB Enterococcus faecalis (21%), vanA E. faecium (6%), and vanA E. faecalis (2%). The majority of isolates were nonclonal by pulsed-field gel electrophoresis analysis. Multivariate analysis of risk factors in patients with an acceptable screening suggested that being managed by a renal unit (hazard ratio [HR] compared to the results for patients managed in an intensive care unit, 4.6; 95% CI, 1.2 to 17.0 [P = 0.02]) and recent administration of either ticarcillin-clavulanic acid (HR, 3.6; 95% CI, 1.1 to 11.6 [P = 0.03]) or carbapenems (HR, 2.8; 95% CI, 1.0, 8.0 [P = 0.05]), but not vancomycin or broad-spectrum cephalosporins, were associated with acquisition of VRE. The relatively low rates of colonization with VRE, the polyclonal nature of most isolates, and the possible association with the use of broad-spectrum antibiotics are consistent with either the endogenous emergence of VRE or the amplification of previously undetectable colonization with VRE among high-risk patients managed under conditions in which the risk of nosocomial acquisition was minimized.