Leanne B. Gasink

Risk Factors and Clinical Impact of Klebsiella pneumoniae Carbapenemase–Producing K. pneumoniae

BACKGROUND Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae is an emerging pathogen with serious clinical and infection control implications. To our knowledge, no study has specifically examined risk factors for KPC-producing K. pneumoniae or its impact on mortality. METHODS To identify risk factors for infection or colonization with KPC-producing K. pneumoniae, a case-control study was performed. Case patients with KPC-producing K. pneumoniae were compared with control subjects with carbapenem-susceptible K. pneumoniae. A cohort study evaluated the association between KPC-producing K. pneumoniae and in-hospital mortality. RESULTS Fifty-six case patients and 863 control subjects were identified. In multivariable analysis, independent risk factors for KPC-producing K. pneumoniae were (1) severe illness (adjusted odds ratio [AOR], 4.31; 95% confidence interval [CI], 2.25-8.25), (2) prior fluoroquinolone use (AOR, 3.39; 95% CI, 1.50, 7.66), and (3) prior extended-spectrum cephalosporin use (AOR, 2.55; 95% CI, 1.18, 5.52). Compared with samples from other anatomic locations, K. pneumoniae isolates from blood samples were less likely to harbor KPC (AOR, 0.33; 95% CI, 0.12, 0.86). KPC-producing K. pneumoniae was independently associated with in-hospital mortality (AOR, 3.60; 95% CI, 1.87-6.91). CONCLUSIONS KPC-producing K. pneumoniae is an emerging pathogen associated with significant mortality. Our findings highlight the urgent need to develop strategies for prevention and infection control. Limiting use of certain antimicrobials, specifically fluoroquinolones and cephalosporins, use may be effective strategies.

Clinical and Microbiological Outcomes of Serious Infections with Multidrug-Resistant Gram-Negative Organisms Treated with Tigecycline

Eighteen patients received tigecycline as treatment for infection due to multidrug-resistant gram-negative bacilli, including Acinetobacter baumannii and Klebsiella pneumoniae carbapenemase- and extended-spectrum beta-lactamase-producing Enterobacteriaceae. Pretherapy minimum inhibitory concentration values for tigecycline predicted clinical success. Observed evolution of resistance during therapy raises concern about routine use of tigecycline in treatment of such infections when other therapies are available.

Contact Isolation for Infection Control in Hospitalized Patients: Is Patient Satisfaction Affected?

The effects of contact isolation on patient satisfaction are unknown. We performed a cross-sectional survey and found that most patients lack education and knowledge regarding isolation but feel that it improves their care. In multivariable analysis, isolated patients were not less satisfied with inpatient care than were nonisolated patients.

Impact of different methods for describing the extent of prior antibiotic exposure on the association between antibiotic use and antibiotic-resistant infection.

OBJECTIVE Many studies have investigated the association between prior antibiotic use and antibiotic resistance. However, methods used in past studies to describe the extent of prior antibiotic use (eg, use of the 2 categories exposure versus no exposure and measurement of duration of exposure) have not been reviewed. The impact of the use of different methods for quantifying the use of antibiotics is unknown. The objectives of this study were to characterize past approaches to describing the extent of antibiotic use and to identify the impact of the use of different methods on associations between use of specific antibiotics and infection with an antibiotic-resistant-organism. METHODS We conducted a systematic review of studies that investigated risk factors for extended-spectrum beta -lactamase (ESBL)-producing Escherichia coli and Klebsiella species to identify variability in past approaches to describing the extent of antibiotic use. We then reanalyzed a data set from a prior study of risk factors for infection with ESBL-producing E. coli and Klebsiella species. We developed 2 separate multivariable models: 1 in which prior antibiotic use was described as a categorical variable (eg, exposure or no exposure) and 1 in which antibiotic use was described as a continuous variable (eg, measured in antibiotic-days). These models were compared qualitatively. SETTING Large academic medical center. RESULTS The 25 articles included in the systematic review revealed a variety of methods used to describe the extent of prior antibiotic exposure. Only 1 study justified its approach. Results from the 2 multivariable models that used different methodologic approaches differed substantially. Specifically, use of third-generation cephalosporins was a risk factor for infection with ESBL-producing E. coli and Klebsiella species when antibiotic use was described as a continuous variable but not when antibiotic use was described as a categorical variable. CONCLUSIONS There has been no consistent method for assessing the extent of prior antibiotic exposure. The use of different methods may substantially alter the identified antimicrobial risk factors, which has important implications for the resultant interventions regarding antimicrobial use.

Genetic Variants and Susceptibility to Neurological Complications Following West Nile Virus Infection

Abstract To determine genetic factors predisposing to neurological complications following West Nile virus infection, we analyzed a cohort of 560 neuroinvasive case patients and 950 control patients for 13 371 mostly nonsynonymous single-nucleotide polymorphisms (SNPs). The top 3 SNPs on the basis of statistical significance were also in genes of biological plausibility: rs2066786 in RFC1 (replication factor C1) (P = 1.88 × 10−5; odds ratio [OR], 0.68 [95% confidence interval {CI}, .56–.81]); rs2298771 in SCN1A (sodium channel, neuronal type I α subunit) (P = 5.87 × 10−5; OR, 1.47 [95% CI, 1.21–1.77]); and rs25651 in ANPEP (ananyl aminopeptidase) (P = 1.44 × 10−4; OR, 0.69 [95% CI, .56–.83]). Additional genotyping of these SNPs in a separate sample of 264 case patients and 296 control patients resulted in a lack of significance in the replication cohort; joint significance was as follows: rs2066786, P = .0022; rs2298771, P = .005; rs25651, P = .042. Using mostly nonsynonymous variants, we therefore did not identify genetic variants associated with neuroinvasive disease.

Decreased post-transplant survival among heart transplant recipients with pre-transplant hepatitis C virus positivity

BACKGROUND Transplant centers are reluctant to perform heart transplantation in patients with hepatitis C virus (HCV) infection because augmented immunosuppression could potentially increase mortality. However, there have been few studies examining whether HCV infection reduces survival after heart transplantation. METHODS We used data from the the U.S. Scientific Registry of Transplant Recipients to perform a multicenter cohort study evaluating the association between recipient pre-transplant HCV status and survival after heart transplantation. Adults undergoing heart transplantation between January 1, 1993 and December 31, 2007 were eligible to participate. RESULTS Among 20,687 heart transplant recipients (443 HCV-positive and 20,244 HCV-negative) at 103 institutions followed for a mean of 5.6 years, mortality was higher among HCV-positive than HCV-negative recipients (177 [40%] vs 6,367 [31.5%]; p = 0.0001). After matching on propensity score, hospital and gender, the hazard ratio (HR) of death for HCV-positive heart transplant recipients was 1.32 (95% confidence interval [CI] 1.08 to 1.61). Mortality rates were higher among HCV-positive heart transplant recipients at 1 year (9.4% vs 8.2%), 5 years (26.3% vs 22.9%), 10 years (53.1% vs 43.4%) and 15 years (74.8% vs 62.3%) post-transplantation. HRs did not vary by gender or overall number of heart transplantations performed at the center. CONCLUSIONS Pre-transplant HCV positivity is associated with decreased survival after heart transplantation.

Increased incidence of cytomegalovirus infection in high‐risk liver transplant recipients receiving valganciclovir prophylaxis versus ganciclovir prophylaxis

Optimal measures for the prevention of cytomegalovirus (CMV) in high‐risk orthotopic liver transplant (OLT) patients are unknown. The charts of high‐risk OLT recipients with 12 months of follow‐up who were transplanted over a 44‐month period were reviewed. The incidence of CMV disease in CMV‐seropositive donor/CMV‐seronegative recipient patients receiving valganciclovir or ganciclovir prophylaxis was compared. Sixty‐six patients met the inclusion criteria and were treated with 1 of 3 prophylactic regimens: valganciclovir (900 mg daily; 27 patients), oral ganciclovir (1000 mg every 8 hours; 17 patients), or intravenous ganciclovir (6 mg/kg daily; 22 patients). Eight CMV cases occurred, all after completion of the prophylaxis. The combined incidence of CMV disease with intravenous and oral ganciclovir was lower than the incidence in valganciclovir recipients (P = 0.056; relative risk, 4.33; 95% confidence interval, 0.94–19.87). CMV disease occurred in 22.2% of valganciclovir recipients, 4.5% of intravenous ganciclovir recipients, and 5.9% of oral ganciclovir recipients. In conclusion, late‐onset CMV disease occurred more frequently among high‐risk liver transplant recipients treated with valganciclovir prophylaxis. The 4‐fold higher incidence of CMV disease in our study supports the avoidance of valganciclovir for prophylaxis in high‐risk OLT patients. Liver Transpl 15:963–967, 2009.

Risk factors for and impact of infection or colonization with aztreonam-resistant Pseudomonas aeruginosa.

OBJECTIVE To identify risk factors for infection or colonization with aztreonam-resistant Pseudomonas aeruginosa and examine the impact of this organism on mortality. DESIGN A case-control study was performed to identify risk factors for infection or colonization with aztreonam-resistant P. aeruginosa. A cohort study was subsequently performed to examine the impact of aztreonam resistance on outcomes. SETTING A tertiary referral center in southeastern Pennsylvania.Participants. Inpatients with a clinical culture positive for P. aeruginosa between January 1, 1999, and December 31, 2000. RESULTS Of 720 P. aeruginosa. isolates, 183 (25.4%) were aztreonam-resistant and 537 (74.6%) were aztreonam susceptible. In a multivariable model, prior fluoroquinolone use (adjusted odds ratio [aOR], 1.81 [95% confidence interval {CI}, 1.17-2.80]), prior use of an antianaerobic agent (aOR, 1.56 [95% CI, 1.06-2.29]), and renal insufficiency (aOR, 1.59 [95% CI, 1.10-2.29]) were associated with infection or colonization with aztreonam-resistant P. aeruginosa, while older age (aOR, 0.98 [95% CI, 0.97-0.99] per year of age) was negatively associated with infection or colonization with this organism. In-hospital mortality was higher among subjects infected or colonized with aztreonam-resistant P. aeruginosa, compared with those who were infected or colonized with aztreonam-susceptible P. aeruginosa (25.7% vs 16.8%; P=.009), but in multivariable analysis, no significant association was found between infection or colonization with aztreonam-resistant P. aeruginosa and mortality. CONCLUSIONS Curbing the use of fluoroquinolones and antimicrobials with antianaerobic activity may be an effective strategy to limit the emergence of aztreonam-resistant P. aeruginosa.

Isolation precautions for antibiotic-resistant bacteria in healthcare settings.

Purpose of review Emergence of drug-resistant bacteria and new or changing infectious pathogens is an important public health problem. Transmission of these pathogens in an acute care setting may occur frequently if proper precautions are not taken. Despite several guidelines and an abundance of literature on the prevention of transmission of epidemiologically important organisms in the healthcare setting, substantial controversy exists. This review focuses on recent data regarding the use of infection control and isolation precautions. Recent findings New data are available, but the conflict surrounding the use of active surveillance of methicillin-resistant Staphylococcus aureus (MRSA) has not been resolved. The emergence of multidrug-resistant Gram-negative bacteria has prompted a greater interest in infection control strategies for prevention of their spread. Outbreaks of Clostridium difficile have responded to broad infection control initiatives, but further research is required to determine whether the best infection control precautions are being utilized. Summary Effective prevention of the transmission of pathogens within the healthcare system requires a multifaceted approach. Existing guidelines should be used to create institutional policies specific to individual patient populations, problem pathogens and the ability to practically implement various infection control procedures. Despite ongoing study, the use of active surveillance to prevent transmission of MRSA continues to be a complex, controversial and challenging issue.

Risk factors and clinical outcomes of cytomegalovirus disease occurring more than one year post solid organ transplantation.

Cytomegalovirus (CMV) disease typically occurs during the first year after solid organ transplantation, after cessation of antiviral prophylaxis. CMV occurring after the first year is uncommon and not well described.