Antimicrobial Activities of Piperacillin-Tazobactam plus oxyimino-cephalosporins and Gentamicin against Extensively Drug Resistant Non-Carbapenemase producing Enterobacteriaceae Isolated from Immune-compromised Patients in a Nigerian Hospital (original) (raw)
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Enfermedades Infecciosas y Microbiología Clínica, 2017
Introduction: Antimicrobial resistance in Enterobacteriaceae is increasing worldwide and is making treating infections caused by multidrug-resistant Enterobacteriaceae a challenge. The use of -lactam agents is compromised by microorganisms harboring extended-spectrum -lactamases (ESBLs) and other mechanisms of resistance. Avibactam is a non -lactam agent that inhibits clinically relevant -lactamases, such as ESBL and AmpC. The ceftazidime-avibactam combination (CAZ-AVI) was recently approved for use in certain complicated infections, and may provide a therapeutic alternative for infections caused by these microorganisms. Methods: The in vitro activity of CAZ and CAZ-AVI (AVI at a fixed concentration of 4 mg/L) was tested against 250 clinical isolates of Enterobacteriaceae using broth microdilution. EUCAST breakpoint criteria were used for CAZ, and FDA criteria for CAZ-AVI. Clinical isolates included bacteria producing extendedspectrum -lactamases (ESBLs) and acquired AmpC -lactamases (AACBLs). Porin loss in Klebsiella pneumoniae was also evaluated. Results: The combination of AVI with CAZ displayed excellent activity against clinical isolates of ESBLproducing Escherichia coli and Klebsiella pneumoniae, rendering all the ceftazidime-resistant isolates susceptible to ceftazidime. CAZ-AVI retained activity against porin-deficient isolates of K. pneumoniae producing ESBLs, AACBLs, or both, although MIC values were higher compared to porin-expressing isolates. CAZ-AVI rendered all the ceftazidime-resistant AACBL-producing Enterobacteriaceae tested susceptible to ceftazidime. Conclusion: CAZ-AVI showed potent in vitro activity against clinical isolates of Enterobacteriaceae producing ESBLs and/or AACBLs, including K. pneumoniae with loss of porins.
European Journal of Clinical Microbiology & Infectious Diseases, 2015
The influence of hospital use of antibiotics other than cephalosporins and fluoroquinolones on extendedspectrum beta-lactamase (ESBL) resistance among Enterobacteriaceae is poorly known. Our objective was to explore the association between ESBL and hospital use of various classes of antibacterial agents. The relationship between monthly use of 19 classes of antibacterial agents and incidence of nosocomial ESBL-producing Enterobacteriaceae in a French hospital was studied between 2007 and 2013. Five antibiotic classes were significantly and independently associated with ESBL resistance. Uses of tetracyclines (link esti-mate±SE, 0.0066±0.0033), lincosamides (0.0093±0.0029), and other antibacterial agents (0.0050±0.0023) were associated with an increased incidence, while nitrofurantoin (−0.0188±0.0062) and ticarcillin and piperacillin with or without enzyme inhibitor (−0.0078±0.0031) were associated with a decreased incidence. In a multivariate model including 3rd-and 4th-generation cephalosporins, fluoroquinolones, amoxicillin, and amoxicillin-clavulanate, 3rd-and 4th-generation cephalosporins (0.0019 ± 0.0009) and fluoroquinolones (0.0020±0.0008) were associated with an increased ESBL resistance, whereas amoxicillin and amoxicillin-clavulanate were not. Hospital use of tetracyclines and lincosamides may promote ESBL resistance in Enterobacteriaceae. Nitrofurantoin and ticarcillin and piperacillin with or without enzyme inhibitor should be considered as potential alternatives to broad-spectrum cephalosporins and fluoroquinolones to control the diffusion of ESBL resistance.
Infection and Drug Resistance, 2022
Background: Multi-drug resistant Enterobacteriaceae (MDR-E), primarily extended-spectrum beta-lactamase producers (ESBLs), have emerged as a major public health concern. This study aimed to determine the prevalence of multi-drug resistance and extendedspectrum beta-lactamase-producing Enterobacteriaceae among hospitalized patients presumptive for bacterial infections at Debre Berhan Comprehensive Specialized Hospital, Ethiopia. Methods: A hospital-based cross-sectional study was conducted from January to May 2021. A total of 384 hospitalized patients presumptive for bacterial infections were included in the study. Urine, wound, blood, stool, and sputum samples were collected and cultured on MacConkey agar, Cysteine Lactose Electrolyte Deficient medium, and Blood agar. Identification was done using a panel of biochemical tests. The antimicrobial susceptibility test was done by disc diffusion. Screening of ESBL production was done by using cefotaxime and ceftazidime and confirmed by the combination disk method per clinical laboratory standard institute guidelines. Data analysis was performed by Statistical Package for Social Sciences software version 25, and a P-value ≤0.05 was considered as statistically significant. Results: Out of 384 study participants, a total of 164 Enterobacteriaceae were isolated. The overall multi-drug resistance rate (MDR) was 92.1%. The overall prevalence of ESBL-PE was 104 (63.4%). E. coli 50 (30.5%) and K. pneumoniae 24 (14.6%) were the predominant ESBL producers. The highest ESBL producers E. coli (13.4%) and K. pneumoniae (6.1%) were isolated from urine sample. History of antibiotic use for the last three months (P-value=0.01), admission in neonatal intensive care unit (P-value=0.02), history of hospital stays (P-value=0.01), and chronic disease (P-value=0.04) showed statistically significant association with ESBL-PE infection. Conclusion: The prevalence of MDR-E and ESBL-PE was high. Therefore, strong infection prevention and control measures and careful selection of antibiotics are needed in the study area to block the transmission and infection in the healthcare setting.
Antimicrobial Agents and Chemotherapy, 2006
The spread of extended-spectrum--lactamase (ESBL)-producing organisms, particularly those harboring the CTX-M-type enzymes, both in the hospital and in the community, is difficult to discontinue due to the successful mobilization and evolution of the genetic elements harboring ESBL genes and coresistance rates in these isolates. The activities of tigecycline against 285 non-clonally related isolates (172 from Escherichia coli, 84 from Klebsiella spp., 20 from Enterobacter spp., 5 from Salmonella spp., and 4 from Citrobacter spp.) expressing well-characterized ESBLs and recovered in our hospital and its community area of influence were comparatively assessed (CLSI microdilution). Susceptibility rates for meropenem, imipenem, tigecycline, amikacin, and piperacillin-tazobactam were 100%, 100%, 97.5%, 93.3%, and 93%, respectively. Tigecycline (mode MIC, 0.5 g/ml; MIC 90 , 1 g/ml) was 4-to 256-fold more active than doxycycline and minocycline (mode MIC range, 2 to 128 g/ml). CTX-Ms were the most frequent ESBLs (61.4%), 65.8% in community and 58.6% in nosocomial isolates. CTX-M-9 (22%), CTX-M-14 (15.8%), and CTX-M-10 (14%) were the most represented derivatives. SHV and TEM variants constituted 22.8% and 15.8% of the ESBLs, respectively. Overall coresistance rates were as follows: gentamicin, 27.4%; tobramycin, 27.4%; amikacin, 6.7%; and chloramphenicol, 29.1%. Sulfonamide (61.7%), trimethoprim (52.3%), streptomycin (50.5%), and ciprofloxacin (37.2%) resistance levels were significantly (P < 0.001) associated with CTX-M-9 producers. No tigecycline resistance was observed, although seven Klebsiella pneumoniae isolates exhibited intermediate MICs (4 g/ml). Tigecycline, lacking cross-resistance with other compounds, could represent an opportunity to reduce the intensity of selection for ESBL-producing organisms derived from the use of other antimicrobial agents. However, this in vitro promise requires support from clinical studies.
Journal of Microbiology and Infectious Diseases, 2018
Objective: Antibiotic resistance is a global phenomenon wherein physicians face the most challenging decision to make for the right kind of drug, and its combinations, to tackle the ever growing ESBL and NDM on pathogens. The aim of the study is to understand outcome of hospitalized patients undergoing antibiotic therapy for bacterial infections. These patients are from Kamrup District of Assam, India. Materials and methods: A total of 185 clinical isolates of Escherichia coli and Klebsiella pneumoniae were collected from hospitalized patients of a tertiary care centre presenting symptoms of infection. Upon biochemical identification, their antibiotic susceptibility were assessed; isolates resistant to 3rd or 4th generation cephalosporins or carbapenem were phenotypically and genotypically determined for the production of extended spectrum β-lactamase (ESBL) and carbapenemase. PCR was carried out for CTX-M, TEM, SHV, OXA-48 and New Delhi Metallo-β-lactamase (NDM). Results: Bacterial infection is ubiquitous among male and female patients, with high isolation rate of Escherichia coli among female patients with urinary infection. The highest resistance against E. coli isolates was nalidixic acid (82.9%; p≤0.005) and cefixime (81.4%; p≤0.005). The highest resistance against K. pneumoniae was cefotaxime (77.7%; p≤0.005) and ceftazidime (73%; p≤0.005). Imipenem was the most effective antibiotic while ertapenem was the least. Antibiotic therapy included piperacillin (alone or in combination with tazobactam) for both E. coli and K. pneumoniae infections. Conclusions: Ceftriaxone, amikacin, cefepime, ceftriazone and imipenem were chosen as treatment options; isolates showed intermediate to negligible resistance to these drugs. Tigecycline was administered to patients infected with NDM producing pathogens. J Microbiol Infect Dis 2018; 8(4): 153-157.
African Journal of Microbiology Research, 2013
Extented-spectrum β-lactamase (ESBL) producing Escherichia coli and Klebsiella pneumoniae were shown to be a significant cause of both community-acquired and hospital-acquired infections worldwide. The aim of this study was to compare the epidemiological feature of CTX-M, TEM and SHV producing pathogenic E. coli and K. pneumoniae strains in outpatients and hospitalised patients. Antimicrobial susceptibilities of 551 E. coli and 62 K. pneumoniae strains isolated as pathogenic bacteria were determined by disc diffusion method and ESBLs were characterised by isoelectric focusing and PCR. ESBL production was found in 17.4% of the E. coli and 33.9% of the K. pneumoniae strains. CTX-M type ESBL production was determined in 94.8% of the E. coli and 81% of the K. pneumoniae strains and their sequence analysis revealed the presence of CTX-M-15. Our ESBL producing strains had an excellent susceptibility to imipenem, meropenem and ertapenem. According to the usage of molecular methods, the epidemiologic character of CTX-M type ESBL producing E. coli and K. pneumoniae was found to be related particularly to the presence of CTX-M-15 in outpatients and hospitalised patients. Prudent usage of extented-spectrum cephalosporins is inevitable to reduce the propagation of multidrug resistant ESBL-producing organisms and additionnaly to succeed in the treatment.
African Journal of Microbiology Research, 2013
Extented-spectrum β-lactamase (ESBL) producing Escherichia coli and Klebsiella pneumoniae were shown to be a significant cause of both community-acquired and hospital-acquired infections worldwide. The aim of this study was to compare the epidemiological feature of CTX-M, TEM and SHV producing pathogenic E. coli and K. pneumoniae strains in outpatients and hospitalised patients. Antimicrobial susceptibilities of 551 E. coli and 62 K. pneumoniae strains isolated as pathogenic bacteria were determined by disc diffusion method and ESBLs were characterised by isoelectric focusing and PCR. ESBL production was found in 17.4% of the E. coli and 33.9% of the K. pneumoniae strains. CTX-M type ESBL production was determined in 94.8% of the E. coli and 81% of the K. pneumoniae strains and their sequence analysis revealed the presence of CTX-M-15. Our ESBL producing strains had an excellent susceptibility to imipenem, meropenem and ertapenem. According to the usage of molecular methods, the epidemiologic character of CTX-M type ESBL producing E. coli and K. pneumoniae was found to be related particularly to the presence of CTX-M-15 in outpatients and hospitalised patients. Prudent usage of extented-spectrum cephalosporins is inevitable to reduce the propagation of multidrug resistant ESBL-producing organisms and additionnaly to succeed in the treatment.
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
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.
The Canadian journal of infectious diseases = Journal canadien des maladies infectieuses, 1997
To compare the activity of piperacillin-tazobactam with piperacillin and other parenterally administered antibiotics against aerobic Gram-negative bacilli and Gram-positive cocci isolated from across Canada, and to determine the prevalence of resistance mediated by extended-spectrum cephalosporinases. Sixty-one laboratories participated. Disk diffusion testing was performed in accordance with methods outlined by the National Committee for Clinical Laboratory Standards. Susceptibilities were performed on 8206 strains. Escherichia coli and Klebsiella pneumoniae with reduced susceptibilities to third-generation cephalosporins were screened for extended-spectrum beta-lactamases (ESBLs). Piperacillin-tazobactam was active against 92% of the strains, piperacillin against 81% and ticarcillin-clavulanic acid against 88%. Few differences were observed in the relative susceptibility of strains from teaching or community hospitals, from different anatomic sites or from different regions of the...