ABSTRACT
INTRODUCTION: the purpose of this retrospective multicenter study was to assess whether the risk of developing bloodstream infections (BSI) due to carbapenem-resistant Klebsiella pneumoniae (CRKP) in colonized patients is influenced by the occurrence of BSI due to other pathogens. METHODS: from January 2012 to March 2014, all patients with at least one rectal swab positive for CRKP and at least 30 days of previous hospital stay were included in the study. The primary outcome measure was CRKP BSI, defined as a time-to-event endpoint. The role of potential predictors was evaluated through univariable and multivariable Cox regression analyses, considering previous BSI as a time-dependent variable. RESULTS: during the study period, 353 patients met the inclusion criteria. Thirty-seven developed a CRKP BSI (11%). A higher incidence of CRKP BSI was observed in presence rather than in absence of previous BSI. In the final multivariable model of risk factors for CRKP BSI, multisite colonization (hazard ratio [HR] 13.73, 95% confidence intervals [CI] 3.29-57.32, p < 0.001), ICU stay (HR 3.14, 95% CI 1.19-8.31, p = 0.021), and previous BSI (p = 0.026, with the overall effect being mainly due to Enterococcus spp. BSI vs absence of BSI, HR 6.62, 95% CI 2.11-20.79) were associated with the development of CRKP BSI, while an inverse association was observed for age (HR 0.98, 95% CI 0.95-1.00, p = 0.027). CONCLUSIONS: previous BSI due to other pathogens were associated with an increased risk of CRKP BSI that was independent of other factors in colonized patients with prolonged hospital exposure.
Subject(s)
Anti-Bacterial Agents/pharmacology , Bacteremia/microbiology , Carbapenems/pharmacology , Klebsiella Infections/microbiology , Klebsiella pneumoniae/drug effects , beta-Lactam Resistance , Aged , Bacteremia/epidemiology , Female , Humans , Klebsiella Infections/epidemiology , Klebsiella pneumoniae/isolation & purification , Male , Middle Aged , Retrospective Studies , Risk FactorsABSTRACT
In a prospective cohort of 18 patients treated with boceprevir, we examined the role of boceprevir plasma concentration at the onset of breakthrough during the treatment. Nine patients experienced breakthrough during therapy. The resistance patterns were as follows: S122S/R, I132V, T54A/I132V, V156S/I170A, V36M/T54S/R155K, V36M/R155K and T54/R155K. Boceprevir-S isomer (SCH 534128) median concentration in patients with breakthrough was 48.3 ng/mL (interquartile range 43-58 ng/mL); in others, it was significantly (p 0.019) higher: 151 ng/mL. Low boceprevir plasma concentration can lead to virologic resistance; therapeutic drug monitoring should be used to prevent the onset of viral breakthrough during triple-regimen therapy with boceprevir.
Subject(s)
Antiviral Agents/pharmacokinetics , Hepatitis C, Chronic/drug therapy , Plasma/chemistry , Proline/analogs & derivatives , Adult , Aged , Antiviral Agents/administration & dosage , Cohort Studies , Drug Monitoring , Drug Resistance, Viral , Drug Therapy, Combination/methods , Female , Genotype , Hepacivirus/classification , Hepacivirus/drug effects , Hepacivirus/genetics , Humans , Interferon-alpha/administration & dosage , Male , Middle Aged , Mutation, Missense , Proline/administration & dosage , Proline/pharmacokinetics , Prospective Studies , Ribavirin/administration & dosage , Treatment FailureABSTRACT
Knowledge of carbapenem-resistant Klebsiella pneumoniae (CR-KP) colonization is important to prevent nosocomial spread but also to start prompt adequate antibiotic therapy in patients with suspicion of infection. However, few studies have examined the incidence and risk factors for CR-KP bloodstream infection (BSI) among rectal carriers. To identify risk factors for CR-KP BSI among carriers, we performed a multicentre prospective matched case-control study of all adult CR-KP rectal carriers hospitalized in five tertiary teaching hospitals in Italy over a 2-year period. Carriers who developed CR-KP BSI were compared with those who did not develop subsequent BSI. Overall, 143 CR-KP BSIs were compared with 572 controls without a documented infection during their hospitalization. Multivariate analysis revealed that admission to the Intensive Care Unit (ICU) (OR, 1.65; 95% CI, 1.05-2.59; p 0.03), abdominal invasive procedure (OR, 1.87; 95% CI, 1.16-3.04; p 0.01), chemotherapy/radiation therapy (OR, 3.07; 95% CI, 1.78-5.29; p <0.0001), and number of additional colonization sites (OR, 3.37 per site; 95% CI, 2.56-4.43; p <0.0001) were independent risk factors for CR-KP BSI development among CR-KP rectal carriers. A CR-KP BSI risk score ranging from 0 to 28 was developed based on these four independent variables. At a cut-off of ≥2 the model exhibited a sensitivity, specificity, positive predictive value and negative predictive value of 93%, 42%, 29% and 93%, respectively. Colonization at multiple sites with CR-KP was the strongest predictor of BSI development in our large cohort of CR-KP rectal carriers.
