Ceftazidime-Avibactam Use for Klebsiella pneumoniae Carbapenemase-Producing K. pneumoniae Infections: A Retrospective Observational Multicenter Study.

BACKGROUND: A growing body of observational evidence supports the value of ceftazidime-avibactam (CAZ-AVI) in managing infections caused by carbapenem-resistant Enterobacteriaceae. METHODS: We retrospectively analyzed observational data on use and outcomes of CAZ-AVI therapy for infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) strains. Multivariate regression analysis was used to identify variables independently associated with 30-day mortality. Results were adjusted for propensity score for receipt of CAZ-AVI combination regimens versus CAZ-AVI monotherapy. RESULTS: The cohort comprised 577 adults with bloodstream infections (n = 391) or nonbacteremic infections involving mainly the urinary tract, lower respiratory tract, and intra-abdominal structures. All received treatment with CAZ-AVI alone (n = 165) or with ≥1 other active antimicrobials (n = 412). The all-cause mortality rate 30 days after infection onset was 25% (146/577). There was no significant difference in mortality between patients managed with CAZ-AVI alone and those treated with combination regimens (26.1% vs 25.0%, P = .79). In multivariate analysis, mortality was positively associated with presence at infection onset of septic shock (P = .002), neutropenia (P < .001), or an INCREMENT score ≥8 (P = .01); with lower respiratory tract infection (LRTI) (P = .04); and with CAZ-AVI dose adjustment for renal function (P = .01). Mortality was negatively associated with CAZ-AVI administration by prolonged infusion (P = .006). All associations remained significant after propensity score adjustment. CONCLUSIONS: CAZ-AVI is an important option for treating serious KPC-Kp infections, even when used alone. Further study is needed to explore the drug's seemingly more limited efficacy in LRTIs and potential survival benefits of prolonging CAZ-AVI infusions to ≥3 hours.

Major liver resections, perioperative issues and posthepatectomy liver failure: A comprehensive update for the anesthesiologist.

Significant advances in surgical techniques and relevant medium- and long-term outcomes over the past two decades have led to a substantial expansion in the indications for major liver resections. To support these outstanding results and to reduce perioperative complications, anesthesiologists must address and master key perioperative issues (preoperative assessment, proactive intraoperative anesthesia strategies, and implementation of the Enhanced Recovery After Surgery approach). Intensive care unit monitoring immediately following liver surgery remains a subject of active and often unresolved debate. Among postoperative complications, posthepatectomy liver failure (PHLF) occurs in different grades of severity (A-C) and frequency (9%-30%), and it is the main cause of 90-d postoperative mortality. PHLF, recently redefined with pragmatic clinical criteria and perioperative scores, can be predicted, prevented, or anticipated. This review highlights: (1) The systemic consequences of surgical manipulations anesthesiologists must respond to or prevent, to positively impact PHLF (a proactive approach); and (2) the maximal intensive treatment of PHLF, including artificial options, mainly based, so far, on Acute Liver Failure treatment(s), to buy time waiting for the recovery of the native liver or, when appropriate and in very selected cases, toward liver transplant. Such a clinical context requires a strong commitment to surgeons, anesthesiologists, and intensivists to work together, for a fruitful collaboration in a mandatory clinical continuum.