ABSTRACT There are no data comparing outcomes of patients treated with ceftazidime-avibactam versus comparators for carbapenem-resistant Enterobacteriaceae infections. At our center, treatment Klebsiella pneumoniae bacteremia was associated higher rates clinical success ( P = 0.006) and survival 0.01) than other regimens. Across groups, there were differences in underlying diseases, severity illness, source bacteremia, or strain characteristics (97% produced K. carbapenemase)....

ABSTRACT Ceftazidime-avibactam is a novel β-lactam/β-lactamase inhibitor with activity against carbapenem-resistant Enterobacteriaceae (CRE) that produce Klebsiella pneumoniae carbapenemase (KPC). We report the first cases of ceftazidime-avibactam resistance to develop during treatment CRE infections and identify mechanisms. Ceftazidime-avibactam-resistant K. emerged in three patients after for 10 19 days. Whole-genome sequencing (WGS) longitudinal ceftazidime-avibactam-susceptible...

Thirty-seven carbapenem-resistant Enterobacteriaceae (CRE)-infected patients were treated with ceftazidime-avibactam. Clinical success and survival rates at 30 days 59% (22/37) 76% (28/37), respectively. In 23% (5/22) of clinical successes, CRE infections recurred within 90 days. Microbiologic failure rate was 27% (10/37). Ceftazidime-avibactam resistance detected in 30% (3/10) microbiologic failures.

Background. With an increase in the use of colistin methansulfonate (CMS) to treat carbapenem-resistant Acinetobacter baumannii infections, resistance is emerging. Methods. Patients with infection or colonization due colistin-resistant A. were identified at a hospital system Pennsylvania. Clinical data collected from electronic medical records. Susceptibility testing, pulsed-field gel electrophoresis (PFGE), and multilocus sequence typing (MLST) performed. To investigate mechanism...

Background.The sensitivity of blood cultures for diagnosing invasive candidiasis (IC) is poor.Methods.We performed a validated Candida real-time polymerase chain reaction (PCR) and the Fungitell 1,3-b-D-glucan (BDG) assay on samples collected from prospectively identified patients with IC (n 5 55) hospitalized controls 73).Patients had candidemia 17), deep-seated 33), or both 5).Controls mucosal 5), colonization 48), no known 20).Results.PCR using plasma sera was more sensitive than whole (P...

Data on the use of ceftolozane-tazobactam and emergence resistance during multidrug resistant (MDR)-Pseudomonas aeruginosa infections are limited.We performed a retrospective study 21 patients treated with for MDR-P. infections. Whole genome sequencing quantitative real-time polymerase chain reaction were longitudinal isolates.Median age was 58 years; 9 (43%) transplant recipients. Median simplified acute physiology score-II (SAPS-II) 26. Eighteen (86%) respiratory tract infections; others...

ABSTRACT Ceftazidime-avibactam was used to treat 77 patients with carbapenem-resistant Enterobacteriaceae (CRE) infections at our center. Thirty- and 90-day survival rates were 81% 69%, respectively; these higher than those predicted by SAPS II SOFA scores the onset of infection. Clinical success achieved for 55% but differed site Success lowest pneumonia (36%) bacteremia (75%) urinary tract (88%). By multivariate analysis, ( P = 0.045) receipt renal replacement therapy (RRT) 0.046)...

We identified four blaKPC-3 mutations in ceftazidime-avibactam-resistant clinical Klebsiella pneumoniae isolates, corresponding to D179Y, T243M, D179Y/T243M, and EL165-166 KPC-3 variants. Using site-directed mutagenesis transforming vectors into Escherichia coli, we conclusively demonstrated that mutant encoded enzymes functioned as extended-spectrum β-lactamases; directly conferred higher MICs of ceftazidime-avibactam decreased the carbapenems other β-lactams. Impact was strongest for D179Y...

ABSTRACT Echinocandins are frontline agents against invasive candidiasis (IC), but predictors for echinocandin therapeutic failure have not been well defined. Mutations in Candida FKS genes, which encode the enzyme targeted by echinocandins, result elevated MICs and linked to failures. In this study, broth microdilution FKS1 FKS2 mutations among C. glabrata isolates recovered from patients with IC at our center were correlated retrospectively responses. Thirty-five candidemia 4...

Extensively drug-resistant Acinetobacter baumannii (XDR-Ab) has emerged as a major nosocomial pathogen, but optimal treatment regimens are unknown. Although solid organ transplant (SOT) recipients particularly susceptible to XDR-Ab infections, studies in this population limited. Our objectives were determine the epidemiology, clinical characteristics and outcomes of infections among SOT patients.A retrospective study at our center who colonized or infected with between November 2006 December...

Background. Early diagnosis and treatment of invasive pulmonary aspergillosis (IPA) improves outcome.

We determined imipenem, imipenem-relebactam, ceftazidime, and ceftazidime-avibactam MICs against 100 CRE isolates that underwent whole-genome sequencing. Klebsiella pneumoniae carbapenemases (KPCs) were the most common carbapenemases. Forty-six carried extended-spectrum β-lactamases (ESBLs). With addition of relebactam, imipenem susceptibility increased from 8% to 88%. avibactam, ceftazidime 0% 85%. Neither imipenem-relebactam nor was active metallo-β-lactamase (MBL) producers....

Intra-abdominal candidiasis (IAC) is poorly understood compared to candidemia. We described the clinical characteristics, microbiology, treatment and outcomes of IAC, identified risk factors for mortality. performed a retrospective study adults diagnosed with IAC at our center in 2012–2013. Risk mortality were evaluated using multivariable logistic regression. 163 patients 161 Types intra-abdominal abscesses (55%), secondary peritonitis (33%), primary (5%), infected pancreatic necrosis...

ABSTRACT Voriconazole prophylaxis is common following lung transplantation, but the value of therapeutic drug monitoring unknown. A prospective, observational study transplant recipients ( n = 93) receiving voriconazole was performed. Serum troughs 331) were measured by high-pressure liquid chromatography. The median initial and subsequent 1.91 1.46 μg/ml, respectively. age patient directly correlated with P 0.005). Patients that ≥60 years old cystic fibrosis patients significantly more...

We used meropenem to successfully treat a patient with bacteremia due ceftazidime-avibactam-resistant, meropenem- susceptible Klebsiella pneumoniae that carried mutant blaKPC-3. Meropenem was bactericidal against ceftazidime-avibactam- resistant K isolates in vitro. Nevertheless, the role of carbapenems treating such infections remains uncertain, because resistance is selected readily during passage experiments.

ABSTRACT We measured in vitro activity of plazomicin, a next-generation aminoglycoside, and other aminoglycosides against 50 carbapenem-resistant Klebsiella pneumoniae strains from two centers correlated the results with presence various aminoglycoside-modifying enzymes (AMEs). Ninety-four percent were sequence type 258 (ST258) clones, which exhibited 5 ompK36 genotypes; 80% 10% produced carbapenemase 2 (KPC-2) KPC-3, respectively. Ninety-eight possessed AMEs, including AAC(6′)-Ib (98%),...

ABSTRACT Avibactam is a novel β-lactamase inhibitor with affinity for Klebsiella pneumoniae carbapenemases (KPCs). In combination ceftazidime, the agent demonstrates activity against KPC-producing K. (KPC-Kp). KPC-Kp strains are genetically diverse and harbor multiple resistance determinants, including defects in outer membrane proteins extended-spectrum β-lactamases (ESBLs). Mutations porin gene ompK36 confer high-level carbapenem to strains. Whether specific mechanisms of antimicrobial...

ABSTRACT FKS mutant Candida isolates were recovered from 24% (6/25) of abdominal candidiasis patients exposed to echinocandin. glabrata (29%) and albicans (14%) mutants identified. Multidrug-resistant bacteria 83% infections. Mutations associated with prolonged echinocandin exposure ( P = 0.01), breakthrough infections 0.03), therapeutic failures despite source control interventions (100%). Abdominal is a hidden reservoir for the emergence echinocandin-resistant .

ABSTRACT We reviewed 37 patients treated for bacteremia due to carbapenem-resistant (CR) Pseudomonas aeruginosa . Although 65% of isolates were multiple-drug resistant, therapeutic options available, as all susceptible ≥1 antibiotic. A total 92% received active antimicrobial therapy, but only 57% early therapy (within 48 h). Fourteen-day mortality was 19%. Microbiologic failure occurred in 29%. The Pitt score ( P = 0.046) and delayed 0.027) predictive death microbiologic failure, respectively.

The emergence of Klebsiella pneumoniae carbapenemases (KPCs), β-lactamases that inactivate "last-line" antibiotics such as imipenem, represents a major challenge to contemporary antibiotic therapies. combination ceftazidime (CAZ) and avibactam (AVI), potent β-lactamase inhibitor, an attempt overcome this formidable threat restore the efficacy against Gram-negative bacteria bearing KPCs. CAZ-AVI-resistant clinical strains expressing KPC variants with substitutions in Ω-loop are emerging. We...

Mutations in Candida glabrata FKS genes, which encode the echinocandin target enzyme, are independent risk factors for treatment failures during invasive candidiasis. We retrospectively compared ability of caspofungin susceptibility testing methods to identify C. mutant isolates and predict outcomes among patients at our center. Eight percent (10/120) sterile-site harbored FKS1 (n = 3) or FKS2 7) mutations, including 32% (10/32) recovered from with prior exposure. Median exposures nonmutant...

Ceftazidime-avibactam resistance is mediated by blaKPC-3 mutations, which restore carbapenem susceptibility. We subjected Klebsiella pneumoniae isolates with different mutations (n = 5) or wild-type 2) to serial passages meropenem. The meropenem MIC against each isolate increased. Mutations in the ompK36 porin gene evolved 5 isolates. Among D179Y substitutions KPC-3, reverted wild type, were replaced new retained. Carbapenem treatment of ceftazidime-avibactam-resistant K. infections may...

The carbapenem class of antibiotics is invaluable for the treatment selected multidrug-resistant Gram-negative pathogens. continued transmission carbapenem-resistant bacteria such as ST258 K. pneumoniae serious global public health concern, options these infections are limited. This genomic epidemiologic investigation traced natural history in a single care setting over nearly decade. We found that distinct subpopulations have caused both device-associated and ward-associated outbreaks, some...