Meropenem-Vaborbactam as Salvage Therapy for Ceftazidime-Avibactam-, Cefiderocol-Resistant ST-512 Klebsiella pneumoniae-Producing KPC-31, a D179Y Variant of KPC-3

A 68-year-old man had recurrent bacteremia by Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae resistant to ceftazidime-avibactam and cefiderocol. The sequencing of a target region showed that it harbored a KPC-3 variant enzyme (D179Y; KPC-31), which confers resistance to ceftazidime-avibactam and restores meropenem susceptibility. The patient was successfully treated with meropenem-vaborbactam

Rapid detection of intestinal carriage of Klebsiella pneumoniae producing KPC carbapenemase during an outbreak

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Carbapenem-Sparing Antibiotic Regimens for Infections Caused by Klebsiella pneumoniae Carbapenemase-Producing K. pneumoniae in Intensive Care Unit

A carbapenem-sparing regimen of tigecycline plus gentamicin or colistin was effective for treating 24 of 26 (92%) Klebsiella pneumoniae carbapenemase-producing K. pneumoniae infectious episodes in 22 polytrauma intensive care unit patients without comorbidities. The 30-day crude mortality rate was 14%. Regimens were considered appropriate in 12% of episodes according to the Vitek 2 System and in 100% based on E-test

Synergistic Activity of Colistin plus Rifampin against Colistin-Resistant KPC-Producing Klebsiella pneumoniae

Infections caused by carbapenem-resistant KPC-producing Klebsiella pneumoniae are responsible for high rates of mortality and represent a major therapeutic challenge, especially when the isolates are also resistant to colistin. We used the checkerboard method to evaluate the synergistic activity of 10 antibiotic combinations against 13 colistin-resistant KPC-producing K. pneumoniae isolates (colistin MIC range of 8 to 128 mg/liter). Colistin plus rifampin was the only combination that demonstrated consistent synergistic bacteriostatic activity against 13/13 strains tested, reducing the colistin MIC below the susceptibility breakpoint (MIC<2 mg/liter) in 7/13 strains at rifampin concentrations ranging from 4 to 16 mg/liter. Bactericidal synergistic activity was also documented for 8/13 tested strains. Other antimicrobial combinations with carbapenems, gentamicin, and tigecycline showed variously synergistic results. Colistin plus rifampin also exhibited bacteriostatic synergistic activity against 4/4 colistin-susceptible KPC-producing K. pneumoniae isolates (colistin MIC range of 0.5 to 2 mg/liter) and 4/4 ertapenem-resistant extended-spectrum beta-lactamase (ESBL)-producing K. pneumoniae isolates (ertapenem MIC range of 16 to 32 mg/liter). Collectively, our data suggest that colistin plus rifampin is the most consistently synergistic combination against KPC-producing K. pneumoniae isolates, including colistin-resistant strains. Colistin-rifampin combinations may have a role in the treatment of multidrug-resistant K. pneumoniae and may possibly slow the selection of heteroresistant subpopulations during colistin therapy

Time to appropriate antibiotic therapy is a predictor of outcome in patients with bloodstream infection caused by KPC-producing Klebsiella pneumoniae

BACKGROUND: Bloodstream infections (BSIs) by Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae (Kp) are associated with high mortality. The aim of this study is to assess the relationship between time to administration of appropriate antibiotic therapy and the outcome of patients with BSI due to KPC-Kp hospitalized in intensive care unit (ICU). METHODS: An observational study was conducted in the ICUs of two academic centers in Italy. Patients with KPC-Kp bacteremia hospitalized between January 2015 to December 2018 were included. The primary outcome was the relationship between time from blood cultures (BC) collection to appropriate antibiotic therapy and 30-day mortality. The secondary outcome was to evaluate the association of different treatment regimens with 30-day mortality and a composite endpoint (30-day mortality or nephrotoxicity). A Cox regression analysis to identify factors independently associated with 30-day mortality was performed. Hazard ratio (HR) and 95% confidence interval (CI) were calculated. RESULTS: A total of 102 patients with KPC-Kp BSI were included. The most common sources of infection were intra-abdominal (23.5%), urinary tract (20.6%), and skin and skin structure (17.6%). The 30-day mortality was 45%. Median time to appropriate antibiotic therapy was shorter in patients who survived (8.5\u2009h [IQR 1-36]) versus those who died (48\u2009h [IQR 5-108], p\u2009=\u20090.014). A propensity score matching showed that receipt of an in vitro active therapy within 24\u2009h from BC collection was associated with lower 30-day mortality (HR\u2009=\u20090.36, 95% CI: 0.188-0.690, p\u2009=\u20090.0021). At Cox regression analysis, factors associated with 30-day mortality were primary bacteremia (HR 2.662 [95% CI 1.118-6.336], p\u2009=\u20090.027), cardiovascular disease (HR 2.196 [95% CI 1.082-4.457], p\u2009=\u20090.029), time (24-h increments) from BC collection to appropriate therapy (HR 1.382 [95% CI 1.132-1.687], p\u2009=\u20090.001), SOFA score (HR 1.122 [95% CI 1.036-1.216], p\u2009=\u20090.005), and age (HR 1.030 [95% CI 1.006-1.054], p\u2009=\u20090.012). Ceftazidime-avibactam-containing regimens were associated with reduced risk of composite endpoint (30-day mortality OR nephrotoxicity) (HR 0.231 [95% CI 0.071-0.745], p\u2009=\u20090.014) compared to colistin-containing regimens. CONCLUSIONS: Time to appropriate antibiotic therapy is an independent predictor of 30-day mortality in patients with KPC-Kp BSI. Appropriate antibiotic therapy should begin within 24\u2009h from the collection of BC

Bloodstream infections in patients with rectal colonization by Klebsiella pneumoniae producing different type of carbapenemases: a prospective, cohort study

Objective: To investigate the hypothesis that intestinal colonization by different types of carbapenemase-resistant Klebsiella pneumoniae (CR-Kp) leads to different risks for bloodstream infections (BSI) caused by the same colonizing organism. Methods: Prospective observational study including consecutive CR-Kp rectal carriers admitted to the Pisa University Hospital (December 2018 to December 2019). Patients underwent rectal swabbing with molecular testing for the different carbapenemases at hospital admission and during hospitalization. Rectal carriers were classified as: NDM, KPC, VIM and OXA-48. The primary end point was the rate of BSI by the same colonizing organism in each study group. A multivariate logistic regression analysis was performed to identify factors independently associated with the risk for BSI by the colonizing organism. Results: Of 677 rectal carriers, 382/677 (56.4%) were colonized by NDM, 247/677 (36.5%) by KPC, 39/677 (5.8%) by VIM and 9/677 (1.3%) by OXA-48. Dissemination of NDM-Kp was mostly sustained by ST147, while KPC-Kp belonged to ST512. A higher rate of BSI was documented in NDM rectal carriers compared with KPC rectal carriers (59/382, 15.4% versus 20/247, 8.1%, p 0.004). Incidence rates of BSI per 100 patients/month were significantly higher in the NDM group (22.33, 95% CI 17.26-28.88) than in the KPC group (9.56, 95% CI 6.17-14.82). On multivariate analysis, multi-site extraintestinal colonization, solid organ transplantation, invasive procedures, intravascular device, admission to intensive care unit, cephalosporin, fluoroquinolones and NDM rectal colonization (OR 3.27, 95% CI 1.73-6.18, p &lt; 0.001) were independently associated with BSI. Conclusions: NDM-Kp was associated with increased risk of BSI compared with KPC-Kp. This finding seems to be strongly related to the high-risk clone ST147