piperacillin--tazobactam-drug-combination and Acinetobacter-Infections

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Anti-Bacterial Agents; Aspirin; Carbapenems; COVID-19; COVID-19 Drug Treatment; Critical Illness; Drug Resistance, Multiple, Bacterial; Female; Hospital Mortality; Humans; Intensive Care Units; Klebsiella Infections; Klebsiella pneumoniae; Length of Stay; Male; Middle Aged; Opportunistic Infections; Piperacillin, Tazobactam Drug Combination; Pneumonia; Retrospective Studies; SARS-CoV-2; Steroids; Survival Analysis; Treatment Outcome

Implementing a mouse model of Acinetobacter baumannii (AB) digestive colonization and studying the propensity of an intestinal reservoir of AB to be at the origin of pneumonia.. After a disruption of the digestive flora by piperacillin-tazobactam, two multidrug-resistant AB strains were intranasally inoculated to two cohorts of ten mice daily. For each strain, five mice were rendered transiently neutropenic.. One strain persisted several weeks in the digestive tract, even after stopping piperacillin-tazobactam injections, leading to the hypothesis that some AB strains can authentically colonize the gut. Most of the immunocompromised mice experienced clinical signs and positive lung cultures, which were associated with positive spleen cultures, an argument in favor of bacterial translocation.

Topics: Acinetobacter; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Bacterial Translocation; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Gastrointestinal Tract; Immunosuppression Therapy; Lung; Mice; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial

Acinetobacter pittii is a nosocomial pathogen rarely involved in community-acquired infections. We report for the first time that A. pittii can be responsible for cavitary community-acquired pneumonia and study its virulence, and discuss its pathogenesis and treatment options.. A 45-year-old woman with a history of smoking and systemic lupus was admitted to Nimes University Hospital (France) with coughing and sputum lasting for three weeks. Thoracic CT scanner showed cavitary pneumonia. Broncho-alveolar lavage cultures found community-acquired Acinetobacter calcoaceticus-baumannii complex. The clinical outcome was favourable after twenty-one days of antimicrobial treatment by piperacillin/tazobactam and amikacin then cefepime. Multilocus sequence typing (MLST) analyses identified an A. pittii ST249. Despite the atypical clinical presentation with an unexpected partial destruction of lung parenchyma, we found very low virulence potential of the A. pittii strain with nematode killing assays and biofilm formation test. The median time required to kill 50% of the nematodes was 7 ± 0.3 days for A. pittii ST249, 7 ± 0.2 days for A. baumanii NAB ST2 and 8 ± 0.2 days for E. coli OP50, (p > 0,05). A. pittii ST249 showed significantly slower biofilm formation than A. baumanii NAB ST2: BFI = 8.83 ± 0.59 vs 3.93 ± 0.27 at 2 h (p < 0.0001), BFI = 6.3 ± 0.17 vs 1.87 ± 0.12 at 3 h (p < 0.0001) and BFI = 3.67 ± 0.41 vs 1.7 ± 0.06 after 4 h of incubation (p < 0.01).. Community-acquired A. pittii should be considered as possible cause of sub-acute cavitary pneumonia particularly in a smoking and/or immunocompromised patient despite its low virulence potential.

Topics: Acinetobacter; Acinetobacter Infections; Amikacin; Animals; Caenorhabditis elegans; Community-Acquired Infections; Cross Infection; Female; France; Humans; Middle Aged; Multilocus Sequence Typing; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial; Virulence

The prevalence and antibiotic resistance of Acinetobacter spp. from fifty samples of meat (chicken, turkey, beef and pork) were evaluated. Acinetobacter spp. was recovered from all samples and the clonal relatedness of 223 isolates identified to belong to the genus Acinetobacter was established by PFGE. A high genetic diversity was observed and 166 isolates from different samples, 141 representing different PFGE profiles, were further identified to the species level by rpoB gene sequencing. Thirteen distinct Acinetobacter species were identified among 156 isolates. The remaining ten isolates may represent three putatively novel species since rpoB sequence homologies with type strains of all available described Acinetobacter species, were <95%. The most common species was Acinetobacter guillouiae with a prevalence of 34.9%. However 18.7% of the strains belong to the Acinetobacter baumannii group (n=31) which include the species Acinetobacter baumannii (n=7), Acinetobacter pittii (n=12), Acinetobacter seifertii (n=8) and Acinetobacter nosocomialis (n=4) that are the species most frequently associated with nosocomial infections worldwide. In general, strains were resistant to some of the antimicrobials most frequently used to treat Acinetobacter infections such as piperacillin-tazobactam (64.9% of strains resistant), ceftazidime (43.5%), ciprofloxacin (42.9%), as well as to colistin (41.7%) and polymyxin B (35.1%), the last-resort drugs to treat infections caused by multidrug-resistant Acinetobacter. The percentage of resistant strains to trimethoprim-sulfamethoxazole, tetracycline, aminoglycosides (amikacin and tobramycin) and ampicillin-sulbactam was >10% (23.2%, 23.2%, 14.3%, 12.5%, 12.5%, respectively). However, resistances to meropenem, imipenem and minocycline were only sporadically observed (8.3%, 1.2% and 1.2%, respectively). Overall, 51.2% of the strains were considered as multidrug-resistant (MDR) and 9.6% as extensively drug-resistant (XDR). The prevalence of MDR strains within the A. baumannii group (38.7%) was lower than the prevalence within the others species identified (54.1%). Therefore, food of animal origin may be a vehicle of spread Acinetobacter strains resistant to several antibiotics in the community and in the hospital setting environment. This may led to nosocomial and community-acquired infections in susceptible individuals.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Ampicillin; Animals; Anti-Bacterial Agents; Cattle; Ceftazidime; Chickens; Ciprofloxacin; Cross Infection; DNA-Directed RNA Polymerases; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prevalence; Red Meat; Sulbactam; Swine; Trimethoprim, Sulfamethoxazole Drug Combination

Minocycline-based combination therapy has been suggested to be a possible choice for the treatment of infections caused by minocycline-susceptible Acinetobacter baumannii, but its use for the treatment of infections caused by minocycline-resistant A. baumannii is not well established. In this study, we compared the efficacy of minocycline-based combination therapy (with colistin, cefoperazone-sulbactam, or meropenem) to that of colistin in combination with meropenem for the treatment of minocycline-resistant A. baumannii infection. From 2006 to 2010, 191 (17.6%) of 1,083 A. baumannii complex isolates not susceptible to minocycline from the Taiwan Surveillance of Antimicrobial Resistance program were collected. Four representative A. baumannii isolates resistant to minocycline, amikacin, ampicillin-sulbactam, ceftazidime, ciprofloxacin, cefepime, gentamicin, imipenem, levofloxacin, meropenem, and piperacillin-tazobactam were selected on the basis of the diversity of their pulsotypes, collection years, health care setting origins, and geographic areas of origination. All four isolates had tetB and overexpressed adeABC, as revealed by quantitative reverse transcription-PCR. Among all minocycline-based regimens, only the combination with colistin produced a fractional inhibitory concentration index comparable to that achieved with meropenem combined with colistin. Minocycline (4 or 16 μg/ml) in combination with colistin (0.5 μg/ml) also synergistically killed minocycline-resistant isolates in time-kill studies. Minocycline (50 mg/kg of body weight) in combination with colistin (10 mg/kg) significantly improved the survival of mice and reduced the number of bacteria present in the lungs of mice compared to the results of monotherapy. However, minocycline (16 μg/ml)-based therapy was not effective at reducing biofilm-associated bacteria at 24 or 48 h when its effectiveness was compared to that of colistin (0.5 μg/ml) and meropenem (8 μg/ml). The clinical use of minocycline in combination with colistin for the treatment of minocycline-resistant A. baumannii may warrant further investigation.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Biofilms; Cefepime; Cephalosporins; Colistin; Drug Resistance, Multiple, Bacterial; Gentamicins; Imipenem; Meropenem; Mice; Microbial Sensitivity Tests; Minocycline; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia; Taiwan; Thienamycins

Extensively drug resistant (XDR) Acinetobacter baumannii infections are increasing. Knowledge of risk factors can help to prevent these infections.. We designed a 1∶1∶1 case-case-control study to identify risk factors for XDR A. baumannii bacteremia in Singapore and Thailand. Case group 1 was defined as having infection due to XDR A. baumannii, and case group 2 was defined as having infection due to non-XDR A. baumannii. The control group comprised patients with blood cultures obtained to determine possible infection.. There were 93 patients in each group. Pitt bacteremia score (adjusted odds ratio [aOR], 2.570 [95% confidence interval (CI), 1.528-4.322]), central venous catheters (CVCs; aOR, 12.644 [95% CI, 2.143-74.620]), use of carbapenems (aOR, 54.391 [95% CI, 3.869-764.674]), and piperacillin-tazobactam (aOR, 55.035 [95% CI, 4.803-630.613]) were independently associated with XDR A. baumannii bacteremia. In case group 2, Pitt bacteremia score (aOR, 1.667 [95% CI, 1.265-2.196]) and third-generation cephalosporins (aOR, 2.965 [95% CI, 1.224-7.182]) were independently associated with non-XDR A. baumannii bacteremia. Concurrent infections (aOR, 3.527 [95% CI, 1.479-8.411]), cancer (aOR, 3.172 [95% CI, 1.135-8.865]), and respiratory source (aOR, 2.690 [95% CI, 1.160-6.239]) were associated with an increased risk of 30-day mortality. Survivors received more active empirical therapy (16.7% vs 9.6%; P = .157), had fewer cases of XDR bacteremia (45.8% vs 52.6%; P = .452), and received higher median definitive polymyxin B doses (840,000 units vs 700,000 units; P = .339) CONCLUSIONS: Use of CVC and broad spectrum antibiotics were unique risk factors of XDR A. baumannii bacteremia. Effective antimicrobial stewardship together with use of a CVC bundle may reduce the incidence of these infections. Risk factors of acquisition and mortality may help identify patients for early initiation of polymyxin B therapy.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacteremia; Carbapenems; Case-Control Studies; Central Venous Catheters; Cephalosporins; Coinfection; Drug Resistance, Bacterial; Female; Humans; Male; Microbial Sensitivity Tests; Neoplasms; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Polymyxin B; Respiratory Tract Infections; Risk Factors; Severity of Illness Index; Treatment Outcome

To investigate the mechanism of drug resistance of carbapenems-resistant Acinetobacter baumannii (CRAB) in burn patients and the antimicrobial activity of a combination of drugs against this bacteria in vitro.. A total of 135 strains of Acinetobacter baumannii (AB) from wound excretion, sputum, and venous catheter wall of patients hospitalized in our department from January 2011 to July 2013 were collected individually. Drug resistance of 135 strains of AB to 12 antibiotics commonly-used in clinic was detected using K-B paper diffusion method. Among the CRAB strains, double-disk synergy test was used to screen metallo-β-lactamase (MBL)-producing strains, and the drug resistance rates between MBL-producing strains and non-MBL-producing strains were compared. Minimal inhibitory concentration (MIC), 50% MIC (MIC50), and 90% MIC (MIC90) of cefoperazone/sulbactam, imipenem, cefepime, ampicillin/sulbactam, and amikacin used alone against MBL-producing CRAB were determined by broth microdilution method. MIC, MIC50, and MIC90 of amikacin respectively combined with imipenem, cefoperazone/sulbactam, cefepime, or ampicillin/sulbactam against MBL-producing CRAB were determined by checkerboard method with diluted agar. Fractional inhibitory concentration (FIC) index was calculated to determine the antibacterial effect of each combination of two antibiotics. Synergy with FIC lower than or equal to 0.5, or additivity with FIC higher than 0.5 and lower than or equal to 1.0 was regarded as effective, and indifference with FIC higher than 1.0 and lower than or equal to 2.0 or antagonism with FIC higher than 2.0 was regarded as ineffective. The effective rate was calculated. Data were processed with Chi-square test.. The resistant rates of the 135 strains of AB to imipenem, meropenem, and ceftazidime were high, and those of piperacillin/tazobactam and ampicillin/sulbactam were low. A total of 120 strains of CRAB was screened, accounting for 88.89%, among which the MBL-producing strains accounted for 78.33% (94/120). The resistant rates of MBL-producing strains to piperacillin/tazobactam, imipenem, meropenem, piperacillin, and cefepime were respectively 59.5%, 87.2%, 93.5%, 87.0%, 86.0%, and they were significantly higher than those of non-MBL-producing strains (respectively 43.0%, 81.3%, 87.5%, 78.4%, 64.0%, with χ(2) values from 4.571 to 8.260, P < 0.05 or P < 0.01). Among the inhibition concentrations of each of the 5 antibiotics used alone against MBL-producing strains, MIC, MIC50, and MIC90 of ampicillin/sulbactam were the lowest, respectively 4.00, 16, 64 µg/mL, while those of cefepime were high, respectively 32.00, 128, 512 µg/mL. MIC, MIC50, and MIC90 of amikacin combined with each of the other 4 antibiotics were decreased from 50.00% to 98.44% as compared with that of single administration of each antibiotic. Among the 94 strains of MBL-producing CRAB, the synergic, additive, indifferent, and antagonistic effects were respectively observed in 40, 33, 6, and 15 strains applied with combination of amikacin and ampicillin/sulbactam; 42, 30, 5, 17 strains applied with combination of amikacin and cefoperazone/sulbactam; 38, 15, 19, 22 strains applied with combination of amikacin and cefepime; 34, 2, 37, 21 strains applied with combination of amikacin and imipenem, among which the antibacterial effective rates decreased successively, respectively 77.7%, 76.6%, 56.4%, and 38.3%. The former two rates were respectively significantly higher than the latter two rates (with χ(2) values from 8.618 to 29.889, P values below 0.01).. Production of MBL is the main mechanism of resistance of the CRAB isolated from burn patients hospitalized in our department against carbapenems in about 3 years. The antibacterial effects of amikacin combined with each of the former-mentioned 4 agents are better than those of each of the five antibiotics used singly, and the effects are particularly obvious when combining amikacin with compound agent containing enzyme inhibitors.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Ampicillin; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Carbapenems; Cefepime; Cephalosporins; Drug Resistance; Humans; In Vitro Techniques; Meropenem; Microbial Sensitivity Tests; Penicillanic Acid; Pharmaceutical Preparations; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sulbactam; Thienamycins

Nosocomial infection caused by carbapenem-resistant Acinetobacter baumannii is a worldwide problem and treatment options remain controversial. This study investigated the in vitro effect of various antibiotic combinations against carbapenem-resistant A. baumannii strains.. Antibiotic susceptibility of A. baumannii strains was analysed. In vitro synergistic efficacy of colistin combined with tigecycline, cefoperazone/sulbactam or piperacillin/tazobactam was tested against carbapenem-resistant A. baumannii strains. Synergy studies were performed using an eplisometer test-strip method.. Of the 50 carbapenem-resistant A. baumannii strains tested, 96% were susceptible to colistin and 64% were susceptible to tigecycline. Colistin-tigecycline, colistin-cefoperazone/sulbactam and colistin-piperacillin/tazobactam combinations were found to have synergistic effects against six (12%), two (4%), and one (2%), respectively, of the strains tested.. Colistin combined with tigecycline, cefoperazone/sulbactam or piperacillin/tazobactam revealed synergistic effects in some carbapenem-resistant A. baumannii strains. These results, together with the shortage of treatment options and the risk of developing resistance to colistin, suggest that clinicians should use colistin combined with other antibiotics or β-lactamase inhibitors when treating carbapenem-resistant A. baumannii infection.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamase Inhibitors; Carbapenems; Cefoperazone; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Drug Synergism; Humans; Microbial Sensitivity Tests; Minocycline; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sulbactam; Tigecycline

The Study for Monitoring Antimicrobial Resistance Trends (SMART) is an international surveillance study designed to monitor resistance trends among aerobic and facultative Gram-negative bacilli (GNB) isolated from intra-abdominal infections. During 2003-2010, a total of 20710 GNB isolates were collected at medical centers in China, Hong Kong, Korea, New Zealand, and Taiwan. The susceptibility profiles of 2252 isolates of non-Enterobacteriaceae GNB were determined. At least 10 isolates of a given organism were required for that organism to be included in the analysis. Pseudomonas aeruginosa was the leading organism (49.2% of non-Enterobacteriaceae GNB), followed by Acinetobacter baumannii (21.5%), Aeromonas spp. (11.6%), and Stenotrophomonas maltophilia (9.1%). All the other species/genera made up less than 2%. The rates of susceptibility of the four major organisms were examined for two different time periods and according to whether the isolates had been obtained <48 h after hospitalization or ≥ 48 h after hospital admission. P. aeruginosa, Aeromonas spp., and S. maltophilia showed sustained levels of susceptibility to several antimicrobial agents in the two time periods, whereas A. baumannii exhibited very high rates of resistance to most antimicrobial agents including imipenem. Nosocomial P. aeruginosa and A. baumannii were more resistant than community-acquired pathogens, although this was not the case for Aeromonas spp. and S. maltophilia. Worldwide and regional surveillance is necessary to guide empirical antimicrobial therapy for infections due to non-Enterobacteriaceae GNB.

Topics: Acinetobacter Infections; Aeromonas; Anti-Bacterial Agents; Asia; Australasia; Drug Resistance, Bacterial; Humans; Imipenem; Intraabdominal Infections; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Population Surveillance; Prospective Studies; Pseudomonas aeruginosa; Pseudomonas Infections

The optimal approach for empirical antibiotic therapy in patients with severe sepsis and septic shock remains controversial. A retrospective cohort study was conducted in the intensive care units of a university hospital. The data from 760 patients with severe sepsis or septic shock associated with Gram-negative bacteremia was analyzed. Among this cohort, 238 (31.3%) patients received inappropriate initial antimicrobial therapy (IIAT). The hospital mortality rate was statistically greater among patients receiving IIAT compared to those initially treated with an appropriate antibiotic regimen (51.7% versus 36.4%; P < 0.001). Patients treated with an empirical combination antibiotic regimen directed against Gram-negative bacteria (i.e., beta-lactam plus aminoglycoside or fluoroquinolone) were less likely to receive IIAT compared to monotherapy (22.2% versus 36.0%; P < 0.001). The addition of an aminoglycoside to a carbapenem would have increased appropriate initial therapy from 89.7 to 94.2%. Similarly, the addition of an aminoglycoside would have increased the appropriate initial therapy for cefepime (83.4 to 89.9%) and piperacillin-tazobactam (79.6 to 91.4%). Logistic regression analysis identified IIAT (adjusted odds ratio [AOR], 2.30; 95% confidence interval [CI] = 1.89 to 2.80) and increasing Apache II scores (1-point increments) (AOR, 1.11; 95% CI = 1.09 to 1.13) as independent predictors for hospital mortality. In conclusion, combination empirical antimicrobial therapy directed against Gram-negative bacteria was associated with greater initial appropriate therapy compared to monotherapy in patients with severe sepsis and septic shock. Our experience suggests that aminoglycosides offer broader coverage than fluoroquinolones as combination agents for patients with this serious infection.

Topics: Acinetobacter Infections; Adult; Aged; Aminoglycosides; Anti-Bacterial Agents; Carbapenems; Cefepime; Cephalosporins; Cohort Studies; Drug Therapy, Combination; Escherichia coli Infections; Female; Fluoroquinolones; Gram-Negative Bacterial Infections; Hospital Mortality; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Sepsis; Shock, Septic

The MICs of imipenem, meropenem, piperacillin-tazobactam, cefotaxime, polymixin B and tigecycline against 80 isolates of Acintobacter baumanii from 6 hospitals were determined. A multiplex-PCR was used to detect the genes encoding carbapenemases. Field Inversion Gel Electrophoresis (FIGE) was then used to investigate the genetic relationships among the carbapenem-resistant isolates. Only 7 isolates were resistant to polymixin B and tigecycline (MIC = 16). All isolates were positive for at least 2 carbapenemase genes. At least 10 distinct clones were detected by FIGE. A dominant pattern designated as pulsotype A consisting of 23 isolates was detected from 4 hospitals. The majority of isolates in this pulsotype had a bla(OXA-51/23-like) and bla(OXA-51/24-like) carbapenemase genes and cultured from the patients at burns and ICU. The pan drug resistant isolates belonged to different FIGE patterns. Nosocomial infections with different clones of Acintobacter baumanii occur at Tehran hospitals. However, inter-hospital transmission with certain pulsotypes is likely.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; Cefotaxime; Cross Infection; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Genes, Bacterial; Hospitals; Humans; Imipenem; Iran; Meropenem; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Thienamycins