L. Silvia Munoz-Price

Clinical epidemiology of the global expansion of Klebsiella pneumoniae carbapenemases.

Klebsiella pneumoniae carbapenemases (KPCs) were originally identified in the USA in 1996. Since then, these versatile β-lactamases have spread internationally among Gram-negative bacteria, especially K pneumoniae, although their precise epidemiology is diverse across countries and regions. The mortality described among patients infected with organisms positive for KPC is high, perhaps as a result of the limited antibiotic options remaining (often colistin, tigecycline, or aminoglycosides). Triple drug combinations using colistin, tigecycline, and imipenem have recently been associated with improved survival among patients with bacteraemia. In this Review, we summarise the epidemiology of KPCs across continents, and discuss issues around detection, present antibiotic options and those in development, treatment outcome and mortality, and infection control. In view of the limitations of present treatments and the paucity of new drugs in the pipeline, infection control must be our primary defence for now.

Multicity Outbreak of Carbapenem-Resistant Acinetobacter baumannii Isolates Producing the Carbapenemase OXA-40

ABSTRACT During 2005 we detected a multicity outbreak of infections or colonization due to high-level imipenem-resistant Acinetobacter baumannii (MIC, 64 μg/ml). One hundred isolates from diverse sources were obtained from seven acute-care hospitals and two extended-care facilities; 97% of the isolates belonged to one clone. Susceptibility testing of the first 42 isolates (January to April 2005) revealed broad resistance profiles. Half of the isolates were susceptible to ceftazidime, with many isolates susceptible only to colistin. The level of AmpC β-lactamase expression was stronger in isolates resistant to ceftazidime. PCR and subsequent nucleotide sequencing analysis identified blaOXA-40. The presence of an OXA-40 β-lactamase in these isolates correlated with the carbapenem resistance. By Southern blot analysis, a blaOXA-40-specific probe revealed that the gene was both plasmid and chromosomally located. This is the first time in the United States that such carbapenem resistance in A. baumannii has been attributable to a carbapenemase.

Successful control of an outbreak of Klebsiella pneumoniae carbapenemase-producing K. pneumoniae at a long-term acute care hospital.

OBJECTIVE To determine the effect of a bundle of infection control interventions on the horizontal transmission of Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae during an outbreak. DESIGN Quasi-experimental study. Setting. Long-term acute care hospital. Intervention. On July 23, 2008, a bundled intervention was implemented: daily 2% chlorhexidine gluconate baths for patients, enhanced environmental cleaning, surveillance cultures at admission, serial point prevalence surveillance (PPS), isolation precautions, and training of personnel. Baseline PPS was performed before the intervention was implemented. Any gram-negative rod isolate suspected of KPC production underwent a modified Hodge test and, if results were positive, confirmatory polymerase chain reaction testing. Clinical cases were defined to occur for patients whose samples yielded KPC-positive gram-negative rods in clinical cultures. RESULTS Baseline PPS performed on June 17, 2008, showed a prevalence of colonization with KPC-producing isolates of 21% (8 of 39 patients screened). After implementation of the intervention, monthly PPS was performed 5 times, which showed prevalences of colonization with KPC-producing isolates of 12%, 5%, 3%, 0%, and 0% (P < .001). From January 1, 2008, until the intervention, 8 KPC-positive clinical cases--suspected to be due to horizontal transmission--were detected. From implementation of the intervention through December 31, 2008, only 2 KPC-positive clinical cases, both in August 2008, were detected. From January 1 through December 31, 2008, 8 patients were detected as carriers of KPC-producing isolates at admission to the institution, 4 patients before and 4 patients after the intervention. CONCLUSION A bundled intervention was successful in preventing horizontal spread of KPC-producing gram-negative rods in a long-term acute care hospital, despite ongoing admission of patients colonized with KPC producers.

Prevention of bloodstream infections by use of daily chlorhexidine baths for patients at a long-term acute care hospital.

OBJECTIVE To evaluate the effect of bathing patients with 2% chlorhexidine on the rates of central vascular catheter (CVC)-associated bloodstream infection (BSI) at a long-term acute care hospital (LTACH). DESIGN Quasi-experimental study. SETTING A 70-bed LTACH in the greater Chicago area. PATIENTS All consecutive patients admitted to the LTACH during the period from February 2006 to February 2008. METHODS For patients at the LTACH, daily 2% chlorhexidine baths were instituted during the period from September 2006 until May 2007 (ie, the intervention period). A preintervention period (in which patients were given daily soap-and-water baths) and a postintervention period (in which patients were given daily nonmedicated baths and weekly 2% chlorhexidine baths) were also observed. The rates of CVC-associated BSI and ventilator-associated pneumonia were analyzed for the intervention period and for the pre- and postintervention periods. RESULTS The rates of CVC-associated BSI were 9.5, 3.8, and 6.4 cases per 1,000 CVC-days during the preintervention, intervention, and postintervention periods, respectively. By the end of the intervention period, there was a net reduction of 99% in the CVC-associated BSI rate. No changes were seen in the rates of ventilator-associated pneumonia during the preintervention and intervention periods. CONCLUSION Daily chlorhexidine baths appeared to be an effective intervention to reduce rates of CVC-associated BSI in an LTACH.

Long-term acute care hospitals.

Long-term acute care hospitals (LTACHs) are health care facilities that admit complex patients with acute care needs (eg, mechanical ventilator weaning, administration of intravenous antibiotics, and complex wound care) for a mean duration of stay of 25 days. LTACHs are different than nursing homes and were initially created in the 1990s in an effort to decrease Medicare costs by facilitating prompt discharge from intensive care units of patients with difficulty weaning mechanical ventilation; however, current admission diagnoses are quite broad. Patients admitted to these facilities have multiple comorbidities and are at risk for colonization with multidrug-resistant organisms. LTACH patients have been shown to have high rates of hospital-acquired infections, including central vascular catheter-associated bloodstream infection and ventilator-associated pneumonia. In addition, LTACHs have been implicated in various regional outbreaks of multidrug-resistant organisms. This review summarizes the limited amount of scientific literature on LTACHs while highlighting their infection control problems, as well as the role LTACHs play on regional outbreaks.

The Efficacy of Daily Bathing with Chlorhexidine for Reducing Healthcare-Associated Bloodstream Infections: A Meta-analysis

DESIGN Systematic review and meta-analysis of randomized controlled trials and quasi-experimental studies to assess the efficacy of daily bathing with chlorhexidine (CHG) for prevention of healthcare-associated bloodstream infections (BSIs). SETTING Medical, surgical, trauma, and combined medical-surgical intensive care units (ICUs) and long-term acute care hospitals. PARTICIPANTS Inpatients. METHODS Data on patient population, diagnostic criteria for BSIs, form and concentration of topical CHG, incidence of BSIs, and study design were extracted. RESULTS One randomized controlled trial and 11 nonrandomized controlled trials reporting a total of 137,392 patient-days met the inclusion criteria; 291 patients in the CHG arm developed a BSI over 67,775 patient-days, compared with 557 patients in the control arm over 69,617 catheter-days. CHG bathing resulted in a reduced incidence of BSIs: the pooled odds ratio using a random-effects model was 0.44 (95% confidence interval, 0.33-0.59; [Formula: see text]). Statistical heterogeneity was moderate, with an I(2) of 58%. For the subgroup of studies that examined central line-associated BSIs, the odds ratio was 0.40 (95% confidence interval, 0.27-0.59). CONCLUSIONS Daily bathing with CHG reduced the incidence of BSIs, including central line-associated BSIs, among patients in the medical ICU. Further studies are recommended to determine the optimal frequency, method of application, and concentration of CHG as well as the comparative effectiveness of this strategy relative to other preventive measures available for reducing BSIs. Future studies should also examine the efficacy of daily CHG bathing in non-ICU populations at risk for BSI.

Emergence of KPC-Producing Pseudomonas aeruginosa in the United States

Recent years have shown the emergence and dissemination of isolates of Enterobacteriaceae producing carbapenemases in different parts of the world (3). In many cases, those carbapenemases were KPC -lactamases (5). Those enzymes hydrolyze all -lactams, including carbapenems at a significant level, with the exception of cephamycins. The blaKPC-like genes have been reported most often from enterobacterial species (mostly Klebsiella pneumoniae species) recovered from several states in the United States (5). Besides the United States, KPC-producing K. pneumoniae isolates are found to be endemic in Greece and Israel, and there are, in addition, scattered reports from all over the world, including Western Europe, China, and South and Central America (5). In Colombia, the first identification of KPC-2-positive Pseudomonas aeruginosa isolates has been reported (6). We describe here the first identification of a KPC-producing P. aeruginosa isolate now in the United States. In October 2009, a 68-year-old African-American man with history of diabetes and hypertension was admitted with a myocardial infarction to a 1,500-bed teaching hospital in south Florida. Mechanical ventilation was required upon admission to the medical intensive care unit. He did not report any recent history of hospitalization or travel. The patient received an empirical antibiotic therapy consisting of ceftriaxone and vancomycin. Four weeks after admission, he developed hypothermia and blood and urine cultures grew P. aeruginosa. The patient subsequently received an empirical therapy based on meropenem. MICs of the P. aeruginosa P13 isolate measured by the Etest method (AB Biodisk, Solna, Sweden) and interpreted according to CLSI standards showed multidrug resistance including resistance to all carbapenems (carbapenem MICs of 256 g/ml) (2). That isolate remained susceptible only to amikacin, gentamicin, and colistin. Consequently, the therapy was based on colistin and amikacin, and his subsequent blood cultures remained negative. Molecular investigations were then performed on this isolate. PCR primers were used for the detection of Ambler class A and class B -lactamase genes, followed by sequencing, which identified the blaKPC-2 -lactamase gene coding for carbapenemase KPC-2 (8). Analysis of the plasmid content of P. aeruginosa isolate 13 identified a single plasmid of ca. 66 kb that was successfully transferred to Escherichia coli by electroporation, with a selection performed on amoxicillin (100 g/ml)containing agar plates. The E. coli transformants expressing KPC-2 showed a 3-fold increase of MICs for imipenem, meropenem, and ertapenem, but they did not show any additional non--lactam resistance. PCR mapping performed as described previously (3) showed that the blaKPC-2 gene was part of the Tn4401b transposon originally identified from a K. pneumoniae isolate from New York (4) and also identified from the clonally related Colombian P. aeruginosa isolates (6). Pulsed-field gel electrophoresis (PFGE) performed as described previously, however, indicated that P. aeruginosa isolate P13 was clonally unrelated to P. aeruginosa PA2404 from Colombia (data not shown). This is the first identification of a KPC-producing P. aeruginosa isolate in the United States. It is noteworthy that it did not correspond to an imported case. It therefore remains to be evaluated to what extent KPC-type enzymes have spread in P. aeruginosa in the United States, since the phenotypic detection of production of that carbapenemase remains impossible. Use

Clinical Outcomes of Carbapenem-Resistant Acinetobacter baumannii Bloodstream Infections: Study of a 2-State Monoclonal Outbreak

OBJECTIVE To characterize the clinical outcomes of patients with bloodstream infection caused by carbapenem-resistant Acinetobacter baumannii during a 2-state monoclonal outbreak. DESIGN Multicenter observational study. Setting. Four tertiary care hospitals and 1 long-term acute care hospital. METHODS A retrospective medical chart review was conducted for all consecutive patients during the period January 1, 2005, through April 30, 2006, for whom 1 or more blood cultures yielded carbapenem-resistant A. baumannii. RESULTS We identified 86 patients from the 16-month study period. Their mortality rate was 41%; of the 35 patients who died, one-third (13) had positive blood culture results for carbapenem-resistant A. baumannii at the time of death. Risk factors associated with mortality were intensive care unit stay, malignancy, and presence of fever and/or hypotension at the time blood sample for culture was obtained. Only 5 patients received adequate empirical antibiotic treatment, but the choice of treatment did not affect mortality. Fifty-seven patients (66.2%) had a single positive blood culture result for carbapenem-resistant A. baumannii; the only factor associated with a single positive blood culture result was the presence of decubitus ulcers. Interestingly, during the study period, a transition from single to multiple positive blood culture results was observed. Four patients, 3 of whom were in a burn intensive care unit, were bacteremic for more than 30 days (range, 36-86 days). CONCLUSIONS To our knowledge, this is the first time a study has described 2 patterns of bloodstream infection with A. baumannii: single versus multiple positive blood culture results, as well as a subset of patients with prolonged bacteremia.

Decreasing operating room environmental pathogen contamination through improved cleaning practice

OBJECTIVE Potential transmission of organisms from the environment to patients is a concern, especially in enclosed settings, such as operating rooms, in which there are multiple and frequent contacts between patients, providers hands, and environmental surfaces. Therefore, adequate disinfection of operating rooms is essential. We aimed to determine the change in both the thoroughness of environmental cleaning and the proportion of environmental surfaces within operating rooms from which pathogenic organisms were recovered. DESIGN Prospective environmental study using feedback with UV markers and environmental cultures. SETTING A 1,500-bed county teaching hospital. PARTICIPANTS Environmental service personnel, hospital administration, and medical and nursing leadership. RESULTS The proportion of UV markers removed (cleaned) increased from 0.47 (284 of 600 markers; 95% confidence interval [CI], 0.42-0.53) at baseline to 0.82 (634 of 777 markers; 95% CI, 0.77-0.85) during the last month of observations ([Formula: see text]). Nevertheless, the percentage of samples from which pathogenic organisms (gram-negative bacilli, Staphylococcus aureus, and Enterococcus species) were recovered did not change throughout our study. Pathogens were identified on 16.6% of surfaces at baseline and 12.5% of surfaces during the follow-up period ([Formula: see text]). However, the percentage of surfaces from which gram-negative bacilli were recovered decreased from 10.7% at baseline to 2.3% during the follow-up period ([Formula: see text]). CONCLUSIONS Feedback using Gram staining of environmental cultures and UV markers was successful at improving the degree of cleaning in our operating rooms.

Successful Eradication of a Monoclonal Strain of Klebsiella pneumoniae during a K. pneumoniae Carbapenemase- Producing K. pneumoniae Outbreak in a Surgical Intensive Care Unit in Miami, Florida

We describe the investigation and control of a Klebsiella pneumoniae carbapenemase-producing K. pneumoniae outbreak in a 20-bed surgical intensive care unit during the period from January 1, 2009 through January 1, 2010. Nine patients were either colonized or infected with a monoclonal strain of K. pneumoniae. The implementation of a bundle of interventions on July 2009 successfully controlled the further horizontal spread of this organism.