Use of ceftazidime in the therapy of serious infections, including those due to multiresistant organisms (original) (raw)
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Infectious Diseases and Therapy, 2021
Introduction: A systematic literature review was undertaken to evaluate real-world use of ceftazidime-avibactam for infections due to aerobic Gram-negative organisms in adults with limited treatment options. Methods: Literature searches retrieved peer-reviewed publications and abstracts from major international infectious disease congresses from January 2015 to February 2021. Results were meningitis, febrile neutropenia, osteomyelitis, and cystic fibrosis were also included. Carbapenem-resistant or carbapenemase-producing Enterobacterales (CRE; n = 1718) and carbapenem-resistant, multidrug-resistant (MDR), and extensively drug-resistant Pseudomonas aeruginosa (n = 150) were the most common pathogens. Most publications reported positive outcomes for ceftazidime-avibactam treatment (clinical success rates ranged from 45 to 100% and reported 30-day mortality from 0 to 63%), which were statistically superior versus comparators in some studies. ceftazidime-avibactam resistance emergence occurred infrequently and mostly in Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae strains. Conclusion: This review provides qualitative evidence of successful use of ceftazidime-avibactam for the treatment of hospitalised patients with CRE and MDR P. aeruginosa infections with limited treatment options.
Antibiotics, 2020
Background: Experience in real clinical practice with ceftazidime-avibactam for the treatment of serious infections due to gram−negative bacteria (GNB) other than carbapenem-resistant Enterobacterales (CRE) is very limited. Methods: We carried out a retrospective multicenter study of patients hospitalized in 13 Italian hospitals who received ≥72 h of ceftazidime-avibactam for GNB other than CRE to assess the rates of clinical success, resistance development, and occurrence of adverse events. Results: Ceftazidime-avibactam was used to treat 41 patients with GNB infections other than CRE. Median age was 62 years and 68% of them were male. The main causative agents were P. aeruginosa (33/41; 80.5%) and extended spectrum beta lactamase (ESBL)-producing Enterobacterales (4/41, 9.8%). Four patients had polymicrobial infections. All strains were susceptible to ceftazidime-avibactam. The most common primary infection was nosocomial pneumonia (n = 20; 48.8%), primary bacteremia (n = 7; 17.1%), intra-abdominal infection (n = 4; 9.8%), and bone infection
Antibacterial Activity In Vitro and Regression Studies for Ceftazidime and Ceftriaxone
Acta Pathologica Microbiologica Scandinavica Series B: Microbiology, 2009
The antibacterial activity in vitro of ceftazidime and ceftriaxone was investigated against 575 recent clinical isolates. Both cephalosporins displayed excellent activity against most of the pathogens tested, in particular Gram‐negative bacteria, including Pseudomonas aeruginosa. Apart from the Pseudomonas group, Acinetobacter calcoaceticus and Campylobacter jejuni ceftriaxone was slightly to moderately more active than ceftazidime overall. Ceftriaxone was moderately active against Streptococcus faecalis. Regression lines for the two antibiotics were almost identical. Corresponding to differences in susceptibility, the zone sizes differed for the two drugs with respect to certain bacterial groups, e.g. Pseudomonas sp. and enterococci. Therefore, the two cephalosporins cannot substitute for each other in disc susceptibility testing. Breakpoints for disc tests around 8–16 μg/ml, as suggested in the literature, appear too high considering the beneficial pharmacokinetic properties of th...
Diagnostic Microbiology and Infectious Disease, 1987
The efficacy of ceftazidime alone and combined with amikacin was studied in a rabbit model simulating closed-space infections at locally neutropenic sites. Six strains of Pseudomonas aeruginosa, and six Enterobacteriaceae (two strains each of Klebsiella pneumoniae and Serratia marcescens and one strain each of Escherichia coli and Citrobacter ~reundii) in pooled rabbit serum were each inoculated into separate subcutaneous semipermeable chambers. Intramuscular antibiotic therapy was begun 4 hr later with ceftazidime (50 mg/kg) alone and combined with amikacin (15 mg/kg) for Enterobacteriaceae or ceftazidime (100 mg/kg) alone and combined with amikacin (15 mg/kg)for pseudomonads every 6 hr for 16 doses. Amikacin alone was ineffective for all 12 strains. Ceftazidime alone was successful (>15.5 log~o colony forming units (CFU)/ml decrease from drug-free control) in eliminating five of six Enterobacteriaceae but was not successful against any of the pseudomonads. Ceftazidime plus amikacin was successful against the same five of six Enterobacteriaceae and five of six pseudomonads. The best in vitro tests for the prediction of in vivo outcome were high inoculum (>17 log~o CFU/ml) susceptibility, checkerboard synergism testing, and conventional inoculum time-kill rates at concentrations of antimicrobials simulating extravascular levels obtained in vivo.
Journal of Antimicrobial Chemotherapy, 2014
Ceftazidime-avibactam (MIC 50/90 , 0.12/0.25 g/ml) inhibited 99.9% (20,698/20,709) of Enterobacteriaceae isolates at <8 g/ml. This compound was active against resistant subsets, including ceftazidime-nonsusceptible Enterobacter cloacae (MIC 50/90 , 0.25/ 0.5 g/ml) and extended-spectrum -lactamase (ESBL) phenotype isolates. An ESBL phenotype was noted among 12.4% (1,696/ 13,692 isolates from targeted species) of the isolates, including 776 Escherichia coli (12.0% for this species; MIC 50/90 , 0.12/0.25 g/ml), 721 Klebsiella pneumoniae (16.3%; MIC 50/90 , 0.12/0.25 g/ml), 119 Klebsiella oxytoca (10.3%; MIC 50/90 , 0.06/0.25 g/ ml), and 80 Proteus mirabilis (4.9%; MIC 50/90 , 0.06/0.12 g/ml) isolates. The most common enzymes detected among ESBL phenotype isolates from 2013 (n ؍ 743) screened using a microarray-based assay were CTX-M-15-like (n ؍ 307), KPC (n ؍ 120), SHV ESBLs (n ؍ 118), and CTX-M-14-like (n ؍ 110). KPC producers were highly resistant to comparators, and ceftazidimeavibactam (MIC 50/90 , 0.5/2 g/ml) and tigecycline (MIC 50/90 , 0.5/1 g/ml; 98.3% susceptible) were the most active agents against these strains. Meropenem (MIC 50/90 , <0.06/<0.06 g/ml) and ceftazidime-avibactam (MIC 50/90 , 0.12/0.25 g/ml) were active against CTX-M-producing isolates. Other enzymes were also observed, and ceftazidime-avibactam displayed good activity against the isolates producing less common enzymes. Among 11 isolates displaying ceftazidime-avibactam MIC values of >8 g/ml, three were K. pneumoniae strains producing metallo--lactamases (all ceftazidime-avibactam MICs, >32 g/ml), with two NDM-1 producers and one K. pneumoniae strain carrying the bla KPC-2 and bla VIM-4 genes. Therapeutic options for isolates producing -lactamases may be limited, and ceftazidime-avibactam, which displayed good activity against strains, including those producing KPC enzymes, merits further study in infections where such organisms occur.
Open Forum Infectious Diseases
Background Ceftazidime-avibactam (C-A) is effective against many carbapenem resistant Enterobacteriaceae (CRE) and some carbapenem resistant Pseudomonas aeruginosa (CRPsa), indicated in complicated urinary tract infections (cUTI), complicated intra-abdominal infections (cIAI), and hospital-acquired pneumonia. To our knowledge, in Mexico, there is no data regarding the clinical efficacy (clinical cure) of its use in the treatment of cIAI, cUTI, hospital-acquired pneumonia, and the treatment of CRE and CRPsa. Methods this is a descriptive, observational, retrospective study, including infections in which ceftazidime avibactam was the definitive therapy for CRE and CRPsa, and empiric treatment of cUTI, cIAI, Hospital-acquired pneumonia. The study includes patients from 2 centers, between April 2019 and february 2020. Demographic, clinical and microbiological data were obtained. Clinical cure was defined as the absence of fever, leukocytosis, tachycardia, systolic pressure < 90mmHg o...
Infection and Drug Resistance, 2022
Infections caused by resistant Gram-negative bacteria are becoming increasingly common and now pose a serious public health threat worldwide, because they are difficult to treat due to few treatment options and they are associated with high morbidity and mortality. The combination of ceftazidime with the beta-lactamase inhibitor avibactam-seems to be the right choice in this situation. The aim of the study was to evaluate the activity of ceftazidime/avibactam and other commonly used antibiotics against Enterobacterales and Pseudomonas aeruginosa strains isolated within last years in Poland. Patients and Methods: This study analyzed the antibiotic susceptibility of 1607 Enterobacterales isolates and 543 nonfermenting P. aeruginosa strains collected between 2015 and 2019 in 4 medical laboratories participating in the ATLAS (Antimicrobial Testing Leadership And Surveillance) program in Poland. Unduplicated clinically significant Enterobacterales and P. aeruginosa strains were collected from patients with respiratory, skin and musculoskeletal, genitourinary, abdominal, bloodstream or other infections (ear, eye). Results: The ceftazidime/avibactam combination demonstrates the highest activity against Enterobacterales (98.9%), in both adults and children, including strains presenting MDR (multidrug-resistant) (97.5%) and ESBL (extended spectrum β-lactamase) (96.3%) phenotypes. The activity of ceftazidime/avibactam increased to 100% when only MBL (metallo-β-lactamase)-negative subset of Enterobacterales was considered. This combination also achieved the second highest activity result (89.3%) after colistin in P. aeruginosa, including isolates of MDR (65.9%) and carbapenem-resistant (CR) phenotypes (54.8%). When MBL-positive isolates were excluded, susceptibility rate of P. aeruginosa increased to 94.7%. It is worth to note that susceptibility of the examined P. aeruginosa strains to ceftazidime/avibactam was very high in children (93.3%), especially in a pediatric intensive care unit (94.2%). Conclusion: Enterobacterales and P. aeruginosa included in this analysis presented high susceptibility rates to ceftazidime/avibactam. Ceftazidime/avibactam showed the highest activity against Enterobacterales strains among all antibiotics studied, both for the total population as well as for MDR phenotype and ESBL phenotype. Ceftazidime/avibactam also achieved the second highest activity result against P. aeruginosa strains (including MDR and CR phenotypes). These results are much higher when excluding MBLpositive isolates that exhibit intrinsic resistance to ceftazidime/avibactam.