piperacillin--tazobactam-drug-combination and Escherichia-coli-Infections

Escherichia coli ST131 has emerged as a global epidemic, multidrug-resistant clone of E. coli causing extra-intestinal infections. It is now highly prevalent among fluoroquinolone-resistant and CTX-M ESBL-producing E. coli isolates worldwide. Humans are likely the primary reservoir of ST131. Factors associated with its acquisition include residence in long-term care facilities and recent receipt of antimicrobial agents. E. coli ST131 causes a wide array of infections ranging from cystitis to life-threatening sepsis. Fluoroquinolones and trimethoprim-sulfamethoxazole are no longer adequate options for empiric therapy when E. coli ST131 is suspected from risk factors and local epidemiology. Expanded-spectrum cephalosporins, piperacillin-tazobactam and carbapenems are options to treat serious non-ESBL-producing E. coli ST131 infections, while carbapenems are indicated for ESBL-producing infections. There is a growing interest in reevaluating oral agents including fosfomycin and pivmecillinam for less serious infections such as uncomplicated cystitis.

Topics: Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Cephalosporins; Cystitis; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Humans; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sepsis; United States

The authors had for aim to assess the effectiveness and toxicity of a piperacillin-tazobactam-netilmicin combination, and the possibility of avoiding using glycopeptide, in children with febrile neutropenic episodes induced by chemotherapy.. A retrospective study was made, including children treated for a febrile neutropenic episode (absolute neutrophile count < 0.5 x 10(9)/l) by a piperacillin-tazobactam-netilmicin combination. If fever persisted 48 hours after the beginning of antibiotic therapy, a glycopeptide could be added. The responses to the treatment were defined as follows: 1) total success (no fever or documented infection) at 48 hours and at 72 hours following the beginning of treatment; 2) partial success (apyrexia beyond 72 hours without any therapeutic change); 3) failure (persistent infectious signs 48 hours after the introduction of glycopeptide).. Sixty-nine episodes were assessable, corresponding to 41 patients, treated for a solid tumour (29), an acute leukaemia in remission (11), or a metabolic disease (1). The febrile episodes were divided into fever of unknown origin (71%), microbiologically documented fever (12%), and clinically documented fever (17%). No death occurred, no toxicity was reported. With this antibiotic therapy, total success at 72 hours was observed in 72% in case of fever of unknown origin and 45% in case of documented infections. The success rate reached 84% when a glycopeptide was added (30% of the cases).. The piperacillin-tazobactam-netilmicin combination is very effective and well tolerated in probabilistic treatment of febrile neutropenia induced by chemotherapy, but does not allow to decreasing the frequency of glycopeptide administration.

Topics: Adolescent; Anti-Bacterial Agents; Antineoplastic Agents; Bacterial Infections; Child; Child, Preschool; Clinical Trials as Topic; Drug Combinations; Drug Evaluation; Escherichia coli Infections; Female; Fever; Fever of Unknown Origin; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Infant; Male; Neoplasms; Netilmicin; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Postoperative Complications; Retrospective Studies; Treatment Outcome; Urinary Tract Infections

Although piperacillin-tazobactam (TZP) was shown to be less effective than carbapenems in treating bacteremia due to extended-spectrum β-lactamase-producing (ESBL)-producing organisms in a randomized controlled trial, the fact that many of the causative organisms co-produced inhibitor-resistant OXA-1 along with ESBLs may have influenced the results. In this study, we compared the therapeutic effectiveness of TZP and carbapenem in treating ESBL-producing Escherichia coli bacteremia in areas with low frequency of OXA-1 co-production. Forty patients, 14 in the TZP treatment group and 26 in the carbapenem treatment group, were included in the analysis. There were no significant differences in patient background between the two groups. Urinary tract infection or cholangitis was the source of bacteremia in 26 patients (65%), and the Pitt bacteremia score was zero or one in 35 patients (87.5%). Only four (11.4%) of the 35 causative isolates available for microbiological analysis harbored

Topics: Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Carbapenems; Escherichia coli; Escherichia coli Infections; Humans; Piperacillin, Tazobactam Drug Combination; Treatment Outcome

Extended-spectrum β-lactamases mediate resistance to third-generation cephalosporins (eg, ceftriaxone) in Escherichia coli and Klebsiella pneumoniae. Significant infections caused by these strains are usually treated with carbapenems, potentially selecting for carbapenem resistance. Piperacillin-tazobactam may be an effective "carbapenem-sparing" option to treat extended-spectrum β-lactamase producers.. To determine whether definitive therapy with piperacillin-tazobactam is noninferior to meropenem (a carbapenem) in patients with bloodstream infection caused by ceftriaxone-nonsusceptible E coli or K pneumoniae.. Noninferiority, parallel group, randomized clinical trial included hospitalized patients enrolled from 26 sites in 9 countries from February 2014 to July 2017. Adult patients were eligible if they had at least 1 positive blood culture with E coli or Klebsiella spp testing nonsusceptible to ceftriaxone but susceptible to piperacillin-tazobactam. Of 1646 patients screened, 391 were included in the study.. Patients were randomly assigned 1:1 to intravenous piperacillin-tazobactam, 4.5 g, every 6 hours (n = 188 participants) or meropenem, 1 g, every 8 hours (n = 191 participants) for a minimum of 4 days, up to a maximum of 14 days, with the total duration determined by the treating clinician.. The primary outcome was all-cause mortality at 30 days after randomization. A noninferiority margin of 5% was used.. Among 379 patients (mean age, 66.5 years; 47.8% women) who were randomized appropriately, received at least 1 dose of study drug, and were included in the primary analysis population, 378 (99.7%) completed the trial and were assessed for the primary outcome. A total of 23 of 187 patients (12.3%) randomized to piperacillin-tazobactam met the primary outcome of mortality at 30 days compared with 7 of 191 (3.7%) randomized to meropenem (risk difference, 8.6% [1-sided 97.5% CI, -∞ to 14.5%]; P = .90 for noninferiority). Effects were consistent in an analysis of the per-protocol population. Nonfatal serious adverse events occurred in 5 of 188 patients (2.7%) in the piperacillin-tazobactam group and 3 of 191 (1.6%) in the meropenem group.. Among patients with E coli or K pneumoniae bloodstream infection and ceftriaxone resistance, definitive treatment with piperacillin-tazobactam compared with meropenem did not result in a noninferior 30-day mortality. These findings do not support use of piperacillin-tazobactam in this setting.. anzctr.org.au Identifiers: ACTRN12613000532707 and ACTRN12615000403538 and ClinicalTrials.gov Identifier: NCT02176122.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteremia; Cause of Death; Ceftriaxone; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Thienamycins

Due to limited therapeutic options, the spread of extended-spectrum beta-lactamases (ESBLs) have become a major public health concern. We conducted a prospective, randomized, open-label comparison of the therapeutic efficacy of piperacillin-tazobactam (PTZ), cefepime, and ertapenem in febrile nosocomial urinary tract infection with ESBL-producing Escherichia coli (ESBL-EC).. This study was conducted at three university hospitals between January 2013 and August 2015. Hospitalized adult patients presenting with fever were screened for healthcare-associated urinary tract infection (HA-UTI). When ESBL-EC was solely detected and susceptible to a randomized antibiotic in vitro, the case was included in the final analysis. Participants were treated for 10-14 days with PTZ, cefepime, or ertapenem.. A total of 66 participants were evenly assigned to the PTZ and ertapenem treatment groups. After the recruitment of six participants, assignment to the cefepime treatment group was stopped because of an unexpectedly high treatment failure rate. The baseline characteristics of these participants did not differ from participants in other treatment groups. The clinical and microbiological response to PTZ treatment was estimated to be 94% and was similar to the response to ertapenem treatment. The efficacy of cefepime was 33.3%. In the cefepime group, age, Charlson comorbidity index, genotype, and minimal inhibitory concentration (MIC) did not significantly affect the success of treatment. Similarly, genotype seemed to be irrelevant with respect to clinical outcome in the PTZ group. Expired cases tended to involve septic shock with a high Charlson comorbidity index and high MIC.. Results from this study suggest that PTZ is effective in the treatment of urinary tract infection caused by ESBL-EC when the in vitro test indicates susceptibility. In addition, cefepime should not be used as an alternative treatment for urinary tract infection caused by ESBL-EC.. The trial was registered with the Clinical Research Information Service of Korea Centers for Disease Control and Prevention. (KCT0001895).

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactamase Inhibitors; beta-Lactamases; beta-Lactams; Cefepime; Cephalosporins; Cross Infection; Ertapenem; Escherichia coli; Escherichia coli Infections; Female; Genotype; Humans; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Republic of Korea; Tazobactam; Urinary Tract Infections

Gram-negative bacteria such as Escherichia coli or Klebsiella spp. frequently cause bloodstream infections. There has been a worldwide increase in resistance in these species to antibiotics such as third generation cephalosporins, largely driven by the acquisition of extended-spectrum beta-lactamase or plasmid-mediated AmpC enzymes. Carbapenems have been considered the most effective therapy for serious infections caused by such resistant bacteria; however, increased use creates selection pressure for carbapenem resistance, an emerging threat arising predominantly from the dissemination of genes encoding carbapenemases. Recent retrospective data suggest that beta-lactam/beta-lactamase inhibitor combinations, such as piperacillin-tazobactam, may be non-inferior to carbapenems for the treatment of bloodstream infection caused by extended-spectrum beta-lactamase-producers, if susceptible in vitro. This study aims to test this hypothesis in an effort to define carbapenem-sparing alternatives for these infections.. The study will use a multicentre randomised controlled open-label non-inferiority trial design comparing two treatments, meropenem (standard arm) and piperacillin-tazobactam (carbapenem-sparing arm) in adult patients with bacteraemia caused by E. coli or Klebsiella spp. demonstrating non-susceptibility to third generation cephalosporins. Recruitment is planned to occur in sites across three countries (Australia, New Zealand and Singapore). A total sample size of 454 patients will be required to achieve 80% power to determine non-inferiority with a margin of 5%. Once randomised, definitive treatment will be for a minimum of 4 days, but up to 14 days with total duration determined by treating clinicians. Data describing demographic information, antibiotic use, co-morbid conditions, illness severity, source of infection and other risk factors will be collected. Vital signs, white cell count, use of vasopressors and days to bacteraemia clearance will be recorded up to day 7. The primary outcome measure will be mortality at 30 days, with secondary outcomes including days to clinical and microbiological resolution, microbiological failure or relapse, isolation of a multi-resistant organism or Clostridium difficile infection.. The MERINO trial is registered under the Australian New Zealand Clinical Trials Register (ANZCTR), reference number: ACTRN12613000532707 (registered 13 May 2013) and the US National Institute of Health ClinicalTrials.gov register, reference number: NCT02176122 (registered 24 June 2014).

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Ceftriaxone; Clinical Protocols; Drug Resistance, Microbial; Escherichia coli Infections; Humans; Klebsiella Infections; Meropenem; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sample Size; Thienamycins

Complicated intra-abdominal infections usually mandate prompt surgical intervention supplemented by appropriate antimicrobial therapy. The aim of this study was to demonstrate that ertapenem was not inferior to piperacillin-tazobactam for the treatment of community-acquired intra-abdominal infections. A randomized open-label active-comparator clinical trial was conducted at 48 medical centers on four continents from December 2001 to February 2003. Adult patients with intra-abdominal infections requiring surgery were randomized to receive either ertapenem 1 g daily or piperacillin/tazobactam 13.5 g daily in 3-4 divided doses. The primary analysis of efficacy was the clinical response rate in clinically and microbiologically evaluable patients at the test-of-cure assessment 2 weeks after completion of therapy. All treated patients were included in the safety analysis. Patient demographics, disease characteristics, and treatment duration in both treatment groups were generally similar. The most commonly isolated pathogens at baseline were E coli (greater than 50% of cases in each group) and B fragilis ( approximately 9%). Favorable clinical response rates were 107/119 (90%) for ertapenem recipients and 107/114 (94%) for piperacillin/tazobactam recipients. The frequencies of drug-related adverse events, most commonly diarrhea and elevated serum alanine aminotransferase levels, were similar in both treatment groups. Six of 180 ertapenem recipients (3%) and two of 190 piperacillin/tazobactam recipients (1%) had serious drug-related adverse experiences. In this study, ertapenem and piperacillin/tazobactam were comparably safe and effective treatments for adult patients with complicated intra-abdominal infections.

Topics: Abdomen; Abscess; Adolescent; Adult; Aged; Aged, 80 and over; Alanine Transaminase; Anti-Bacterial Agents; Bacterial Infections; Bacteroides fragilis; Bacteroides Infections; beta-Lactams; Diarrhea; Ertapenem; Escherichia coli Infections; Female; Gastrointestinal Diseases; Humans; Male; Middle Aged; Penicillanic Acid; Peritonitis; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Treatment Outcome

This study aimed to compare treatment outcomes for bloodstream infections (BSI) caused by a piperacillin/tazobactam (PIP/TAZ)-susceptible E. coli among three patient groups: BSI caused by ampicillin/sulbactam (AMP/SLB)-resistant isolates treated with PIP/TAZ, BSI caused by AMP/SLB-sensitive isolates treated with PIP/TAZ, and BSI caused by AMP/SLB-resistant isolates treated with another monotherapy.. This retrospective study was conducted in two academic centres in Europe. Adult patients with E. coli BSI were screened from 2014 to 2020. Inclusion criteria were non-ESBL BSI and initial monotherapy for ≥ 72 h. To reduce the expected bias between the patient groups, propensity score matching was performed. The primary outcome was early treatment response after 72 h and required absence of SOFA score increase in ICU/IMC patients, as well as resolution of fever, leukocytosis, and bacteraemia.. Of the 1707 patients screened, 315 (18.5%) were included in the final analysis. Urinary tract infection was the most common source of BSI (54.9%). Monotherapies other than PIP/TAZ were cephalosporins (48.6%), carbapenems (34.3%), and quinolones (17.1%). Enhanced early treatment response rate was detected (p = 0.04) in patients with BSI caused by AMP/SLB-resistant isolates treated with another monotherapy (74.3%) compared to those treated with PIP/TAZ (57.1%), and was mainly driven by the use of cephalosporins and quinolones (p ≤ 0.03). Clinical success, 28-day mortality, and rate of relapsing BSI did not significantly differ between the groups.. Our study suggests that initial use of PIP/TAZ may be associated with reduced early treatment response in E. coli BSI caused by AMP/SLB-resistant isolates compared to alternative monotherapies.

Topics: Adult; Ampicillin; Anti-Bacterial Agents; Bacteremia; Cephalosporins; Cohort Studies; Escherichia coli; Escherichia coli Infections; Humans; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Quinolones; Retrospective Studies; Sulbactam

Piperacillin-tazobactam (TZP) is a frequently prescribed antibiotic in hospital settings. Reports suggest in vivo efficacy of TZP, despite in vitro resistance of isolates susceptible to cephalosporins. Escherichia coli (E. coli) isolates hyperproducing TEM-1 β-lactamase possess this phenotype. This study investigated the influence of tazobactam (TAZ) concentration on piperacillin (PIP) inhibition of such isolates and compared the in vivo efficacy of TZP with cefotaxime (CTX) in an infection model.. The PIP MICs for E. coli isolates, either hyperproducing TEM-1 because of promoter substitutions (n = 4) or because of gene amplification (n = 2) or producing an inhibitor-resistant TEM-35 (IRT) (n = 1), were determined using increasing concentrations of TAZ in a checkerboard setup. Furthermore, the efficacy of TZP and CTX against the isolates was investigated in a mouse peritonitis model using antibiotic exposures mimicking human conditions. Isolates producing either OXA-48 or CTX-M-15 β-lactamases were included as controls.. Using TAZ concentrations ≤ 64 mg/L, one isolate hyperproducing TEM-1 had a PIP MIC of 8 at TAZ 16 mg/L and two additional isolates at TAZ 64 mg/L. In the mouse peritonitis infection model, reduction of bacterial load in the peritoneum was larger for TZP than CTX only for the CTX-M-15-producing isolate. Larger reductions in bacterial load were observed after CTX treatment than TZP treatment for seven of the eight remaining test isolates.. Piperacillin-tazobactam treatment of E. coli isolates hyperproducing TEM-1 was less effective than CTX treatment and may, for some isolates, be comparable with TZP treatment of isolates producing established resistance markers as IRT or OXA-48.

Topics: Animals; Anti-Bacterial Agents; Antigens, CD; beta-Lactamases; Cefotaxime; Escherichia coli; Escherichia coli Infections; Mice; Microbial Sensitivity Tests; Neoplasm Proteins; Peritonitis; Piperacillin; Piperacillin, Tazobactam Drug Combination; Tazobactam

Urosepsis caused by extended-spectrum β-lactamase (ESBL)-producing Escherichia coli is increasing worldwide. Carbapenems are commonly recommended for the treatment of ESBL infections; however, to minimize the emergence of carbapenem resistance, interest in alternative treatments has heightened.. This study compared pharmacodynamics of piperacillin/tazobactam versus meropenem against ESBL-producing and non-producing E. coli clinical isolates.. E. coli isolates, obtained from national reference laboratory in Bangladesh, were characterized by phenotypic tests, WGS, susceptibility tests and mutant frequency analysis. Three ESBL-producing and two non-producing E. coli were exposed to piperacillin/tazobactam (4.5 g, every 6 h and every 8 h, 30 min infusion) and meropenem (1 g, every 8 h, 30 min infusion) in a hollow-fibre infection model over 7 days.. Piperacillin/tazobactam regimens attained ∼4-5 log10 cfu/mL bacterial killing within 24 h and prevented resistance emergence over the experiment against ESBL-producing and non-producing E. coli. However, compared with 8 hourly meropenem, the 6 hourly piperacillin/tazobactam attained ∼1 log10 lower bacterial kill against one of three ESBL-producing E. coli (CTAP#173) but comparable killing for the other two ESBL-producing (CTAP#168 and CTAP#169) and two non-producing E. coli (CTAP#179 and CTAP#180). The 6 hourly piperacillin/tazobactam regimen attained ∼1 log10 greater bacterial kill compared with the 8 hourly regimen against CTAP#168 and CTAP#179 at 24 h.. Our study suggests piperacillin/tazobactam may be a potential alternative to carbapenems to treat urosepsis caused by ESBL-producing E. coli, although clinical trials with robust design are needed to confirm non-inferiority of outcome.

Topics: Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Escherichia coli; Escherichia coli Infections; Humans; Meropenem; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination

To compare the bacterial killing and emergence of resistance of intermittent versus prolonged (extended and continuous infusions) infusion dosing regimens of piperacillin/tazobactam against two Escherichia coli clinical isolates in a dynamic hollow-fibre infection model (HFIM).. Three piperacillin/tazobactam dosing regimens (4/0.5 g 8 hourly as 0.5 and 4 h infusions and 12/1.5 g/24 h continuous infusion) against a ceftriaxone-susceptible, non-ESBL-producing E. coli 44 (Ec44, MIC 2 mg/L) and six piperacillin/tazobactam dosing regimens (4/0.5 g 8 hourly as 0.5 and 4 h infusions and 12/1.5 g/24 h continuous infusion; 4/0.5 g 6 hourly as 0.5 and 3 h infusions and 16/2 g/24 h continuous infusion) were simulated against a ceftriaxone-resistant, AmpC- and ESBL-producing E. coli 50 (Ec50, MIC 8 mg/L) in a HFIM over 7 days (initial inoculum ∼107 cfu/mL). Total and less-susceptible subpopulations and MICs were determined.. All simulated dosing regimens against Ec44 exhibited 4 log10 of bacterial killing over 8 h without regrowth and resistance emergence throughout the experiment. For Ec50, there was the initial bacterial killing of 4 log10 followed by regrowth to 1011 cfu/mL within 24 h against all simulated dosing regimens, and the MICs for resistant subpopulations exceeded 256 mg/L at 72 h.. Our study suggests that, for critically ill patients, conventional intermittent infusion, or prolonged infusions of piperacillin/tazobactam may suppress resistant subpopulations of non-ESBL-producing E. coli clinical isolates. However, intermittent, or prolonged infusions may not suppress the resistant subpopulations of AmpC- and ESBL-producing E. coli clinical isolates. More studies are required to confirm these findings.

Topics: Anti-Bacterial Agents; Ceftriaxone; Escherichia coli; Escherichia coli Infections; Humans; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination

Bacteria are the commonest etiological factor among the microbes that cause UTIs. The most prevalent bacteria identified in the lab are Escherichia coli, Klebsiella pneumonia and Pseudomonas aeruginosa. Antibiotics are the empiric therapy for such infections but the reoccurrence rate is becoming high owing to the development of resistance due to their irrational and indiscriminate use across the globe. This study was designed on UTI cases of OPD, Medical, Nephrology, Surgical, Main OT, Urology and ICU wards of Allied hospital Faisalabad. 11 antibiotics were used which showed that E. coli is sensitive to Amikacin, Gentamicin, Imipenem, Piperacillin tazobactam, and Polymyxin B. Klebsiella pneumonia showed sensitivity for Amikacin, Gentamicin, Nitrofurantoin, Imipenem, Polymyxin B, Piperacillin tazobactam and Trimethoprim-sulfamethoxazole. While Pseudomonas aurignosa showed resistance to Amikacin, Ciprofloxacin, Gentamicin, Piperacillin tazobactam, Imipenem, and Polymyxin B. E. coli exhibited the highest sensitivity for Piperacillin tazobactam, Klebsiella pneumonia for Imipenem and Pseudomonas aurignosa for Ciprofloxacin. Further, the isolated DNA samples of these microorganisms were confirmed by gel electrophoresis and subjected to molecular characterization by performing trace file and phylogenetic tree analysis.

Topics: Amikacin; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Ciprofloxacin; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Gentamicins; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Nitrofurantoin; Oxacillin; Pakistan; Pipemidic Acid; Piperacillin, Tazobactam Drug Combination; Polymyxin B; Pseudomonas aeruginosa; Pseudomonas Infections; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide. Bacterial co-infections are associated with unfavourable outcomes in respiratory viral infections; however, microbiological and antibiotic data related to COVID-19 are sparse. Adequate use of antibiotics in line with antibiotic stewardship (ABS) principles is warranted during the pandemic. We performed a retrospective study of clinical and microbiological characteristics of 140 COVID-19 patients admitted between February and April 2020 to a German University hospital, with a focus on bacterial co-infections and antimicrobial therapy. The final date of follow-up was 6 May 2020. Clinical data of 140 COVID-19 patients were recorded: The median age was 63.5 (range 17-99) years; 64% were males. According to the implemented local ABS guidelines, the most commonly used antibiotic regimen was ampicillin/sulbactam (41.5%) with a median duration of 6 (range 1-13) days. Urinary antigen tests for Legionella pneumophila and Streptococcus peumoniae were negative in all cases. In critically ill patients admitted to intensive care units (n = 50), co-infections with Enterobacterales (34.0%) and Aspergillus fumigatus (18.0%) were detected. Blood cultures collected at admission showed a diagnostic yield of 4.2%. Bacterial and fungal co-infections are rare in COVID-19 patients and are mainly prevalent in critically ill patients. Further studies are needed to assess the impact of antimicrobial therapy on therapeutic outcome in COVID-19 patients to prevent antimicrobial overuse. ABS guidelines could help in optimising the management of COVID-19. Investigation of microbial patterns of infectious complications in critically ill COVID-19 patients is also required.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Ampicillin; Anti-Bacterial Agents; Antifungal Agents; Antimicrobial Stewardship; Aspergillosis; Azithromycin; Bacterial Infections; Cohort Studies; Coinfection; COVID-19; Enterobacteriaceae Infections; Escherichia coli Infections; Female; Germany; Humans; Klebsiella Infections; Linezolid; Male; Meropenem; Middle Aged; Piperacillin, Tazobactam Drug Combination; Practice Patterns, Physicians'; Retrospective Studies; SARS-CoV-2; Staphylococcal Infections; Streptococcal Infections; Sulbactam; Vancomycin; Young Adult

Limited data exist regarding the efficacy of piperacillin-tazobactam (TZP) for the management of nonbacteremic pyelonephritis caused by extended-spectrum β-lactamase (ESBL)-producing organisms.. We conducted a multicenter observational study comparing clinical outcomes of adults hospitalized with ESBL-producing pyelonephritis who were receiving TZP versus carbapenems, using an inverse probability of treatment weighted propensity score analysis. Patients were eligible for inclusion if all of the following criteria were met: (1) urine cultures growing Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, or Proteus mirabilis at ≥50 000 colony-forming units/mL; (2) identification of an ESBL gene; (3) pyuria (≥10 white blood cells per high powered field in the urine); and (4) dysuria and fever plus at least 1 of the following symptoms: emesis, rigors, hypotension, or flank pain.. There were 186 patients included in the propensity score-weighted cohort; 45 (24%) received TZP and 141 (76%) received a carbapenem. Of these 186 patients, 27% were admitted to the intensive care unit, 48% were immunocompromised, and 45% had underlying urologic abnormalities. There were no differences between the 2 groups in the proportion of patients (20% vs 25%) with recurrent cystitis or pyelonephritis with the same ESBL-producing organism within 30 days (odds ratio, 0.75; 95% confidence interval, .31-1.81; P = .52). There were no differences in the resolution of clinical symptoms by Day 7 or in 30-day mortality. There was 1 (2%) patient in the TZP arm and 11 (8%) patients in the carbapenem arm who had incident carbapenem-resistant organisms isolated within 30 days (P = .09).. TZP may be a reasonable alternative to carbapenems for the management of ESBL-producing pyelonephritis and may mitigate the risk of emergence of carbapenem-resistant organisms, compared with carbapenem therapy.

Topics: Adult; Anti-Bacterial Agents; beta-Lactamases; Escherichia coli Infections; Humans; Klebsiella pneumoniae; Microbial Sensitivity Tests; Piperacillin, Tazobactam Drug Combination; Pyelonephritis; Retrospective Studies

Dengue is an important mosquito-borne tropical viral disease and dual infection, though rare, has been regarded as a risk factor for severe disease and mortality. However, few studies focused on bloodstream infections (BSIs) and empirical antibiotic therapy rarely addressed.. Dengue patients with concurrent or subsequent BSIs between July 1 and December 31, 2015 were included. Clinical information, laboratory data, and drug susceptibility data were collected.. Totally 80 patients, with an in-hospital mortality rate of 32.5%, were included and categorized into three groups. 32 patients in Group I (BSI onset within 48 h after admission), 32 in Group II (between 48 h and one week), and 16 in Group III (more than one week). Patients in Group I were older (mean age: 75.6 vs. 72.6 or 69.6 years; P = 0.01) and had a higher Charlson comorbidity index (3.1 vs. 1.8 or 1.9; P = 0.02) than those in Group II or III. Streptococcus species (28.9%, 11/38) and Escherichia coli (23.7%, 9/38) were major pathogens in Group I. Enterobacteriaceae (38.2%, 13/34) isolates predominated in Group II. Fatal patients more often received inappropriate empirical antibiotic than the survivors (61.5% vs. 35.2%; P = 0.03). According to susceptibility data, pathogens in Group I and II shared similar susceptibility profiles, and levofloxacin, cefepime, or piperacillin/tazobactam, can be empirically prescribed for those hospitalized within one week.. BSI pathogens vary among dengue patients. For adults with dengue and suspected BSI hospitalized within one week, empirical antimicrobial agents are recommended.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Candidemia; Cefepime; Coinfection; Dengue; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli; Escherichia coli Infections; Female; Hospitals; Humans; Levofloxacin; Male; Microbial Sensitivity Tests; Middle Aged; Mortality; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Risk Factors; Staphylococcal Infections; Streptococcus; Taiwan

Topics: Adult; beta-Lactamases; Ceftriaxone; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Gentamicins; Hospitals; Humans; Klebsiella Infections; Klebsiella pneumoniae; Maternal-Fetal Exchange; Piperacillin, Tazobactam Drug Combination; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Infectious; Tanzania; Urinary Tract Infections; Young Adult

To find the most suitable antibiotic against urinary tract infection caused by Extended Spectrum Beta Lactamase producing uropathogens, and the epidemiology of Extended Spectrum Beta Lactamase producers.. The cross-sectional study was conducted at Pir Mehr Ali Shah University of Arid Agriculture, Rawalpindi, Pakistan, from July 2014 to July 2015, and comprised urine samples of patients suffering from urinary tract infection which were cultured on Cysteine Lactose Electrolyte Deficient agar medium. Analysis was done on Muller- Hintonagar plates and optical density was set as 0.1 at 530nm. Antimicrobial sensitivity was tested using Kirby-Bauer disc diffusion method. Further confirmation was done through gram staining and biochemical tests. Extended Spectrum Beta Lactamase production was confirmed through phenotypic methods, including phenotypic confirmatory disc diffusion test, double disc synergy test and Epsilometer test.. Of the 150 samples, 98(65%) showed growth of a total of 114 pathogenic isolates. Escherichia coli was the commonest organism in 94(82%) samples. Piperacillin Tazocin was the most suitable antimicrobial drug in 88(90%) cases. Overall, 23(20%) isolates were producers of Extended Spectrum Beta Lactamase.. Piperacillin Tazocin was found to be the drug of choice for patient suffering from urinary tract infection.

Topics: Adolescent; Adult; Anti-Bacterial Agents; beta-Lactamases; Cross-Sectional Studies; Escherichia coli; Escherichia coli Infections; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Pakistan; Piperacillin, Tazobactam Drug Combination; Proteus; Proteus Infections; Pseudomonas aeruginosa; Pseudomonas Infections; Urinary Tract Infections; Young Adult

To identify plasmid-mediated colistin resistance in clinical Enterobacteriaceae isolates in Oman, where this resistance mechanism has not been encountered yet.. Twenty-two colistin-resistant Enterobacteriaceae clinical isolates collected between July 2014 and June 2016 in a tertiary care hospital in Muscat were screened by PCR for the mcr-1 and mcr-2 genes. The strain identified as mcr-1 positive was genotyped and its antibiotic susceptibility was established. The mcr-1 containing plasmid was mobilized into Escherichia coli K-12 and its sequence was determined.. A single E. coli isolate (OM97) carrying mcr-1 gene was identified, while no strains carrying the mcr-2 gene was found. E. coli OM97 was isolated in June 2016 from blood culture of a male patient with multiple comorbidities. It belonged to ST10. Beyond colistin, it was resistant to amoxicillin-clavulanic acid, piperacillin-tazobactam, amikacin, ciprofloxacin, tetracycline, and cotrimoxazole. The mcr-1 gene was located on a conjugative IncI2-type plasmid of 63722 bp size, which did not harbor any further resistance genes. The genetic surrounding of the mcr-1 gene lacked the ISApl1 element.. Although colistin resistance caused by the mcr-1 gene is not common in our collection of clinical isolates, the occurrence of the plasmid-mediated colistin resistance in an E. coli ST10 strain is of concern as this clonal group was already shown to spread ESBL genes and quinolone resistance worldwide. It is especially worrisome that as the mcr-1 gene occurred in a non-ESBL, carbapenem-susceptible E. coli strain, current susceptibility testing algorithms may not detect its presence.

Topics: Amikacin; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Bacteremia; Ciprofloxacin; Colistin; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Gene Expression; Humans; Membrane Proteins; Microbial Sensitivity Tests; Oman; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Plasmids; Protein Isoforms; Tetracycline; Trimethoprim, Sulfamethoxazole Drug Combination

The efficacy of empirical non-carbapenem antibiotics for extended-spectrum beta-lactamase-producing Enterobacteriaceae bacteremia (ESBL-B) is still inconclusive. We conducted a multicenter retrospective cohort study to evaluate the efficacy of empirical non-carbapenem antibiotics for treating ESBL-B. Electronic medical records of individuals who were diagnosed with ESBL-B were reviewed between January 2010 and December 2014 at four university hospitals in Korea. Patients were classified into non-carbapenem and carbapenem groups according to the empirical antibiotic regimen. Patients treated with appropriate empirical antibiotics and who subsequently received carbapenems as definitive therapy were included in the analysis. The inverse probability of treatment weights, a statistical method that adjusts baseline statistics by giving weights based on propensity score, was used. During the study period, 232 adequately treated patients with ESBL-B were included in the analysis: 49 patients in the non-carbapenem group and 183 in the carbapenem group. The baseline characteristics and severity of infection were similar after propensity score weighting. The 30-day mortality rates for the two groups were not statistically significantly different (non-carbapenems 6.3% and carbapenems 11.4%; P = 0.42). In a multivariate analysis, empirical treatment with non-carbapenem antibiotics was not associated with 30-day all-cause mortality (HR 1.02, 95% CI 0.99-1.06, P = 0.14). In a subgroup analysis, empirical treatment with piperacillin-tazobactam was also not associated with 30-day all-cause mortality (HR 1.21, 95% CI 0.37-4.00, P = 0.75). Appropriate non-carbapenems were not inferior to carbapenems as initial empirical therapy for ESBL-B.

Topics: Aged; Anti-Bacterial Agents; Bacteremia; Carbapenem-Resistant Enterobacteriaceae; Ciprofloxacin; Escherichia coli; Escherichia coli Infections; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Propensity Score; Retrospective Studies; Tertiary Care Centers; Thienamycins; Treatment Outcome

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamase Inhibitors; Escherichia coli; Escherichia coli Infections; Humans; Meropenem; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pseudomonas aeruginosa; Pseudomonas Infections; Thienamycins

Carbapenems are the preferred β-lactamics for treatment for infections caused by enterobacteria producing extended-spectrum β-lactamases (ESBL); however, clinical studies show effectiveness of piperacillin/tazobactam in certain infections by Escherichia coli ESBL producers.. To determine the clinical and micro-biological cure with piperacillin/tazobactam in patients with infections caused by E. coli ESBL producers, CTXM type.. Retrospective descriptive study with adults hospitalized in a university hospital. We included urinary tract infections (UTI), intra-abdominal infections (IAI), soft tissue infections (STI) and/or bacteremia.. We studied 40 patients, where 65% corresponded to UTI, 25% to IAI and 10% were STI. The overall clinical cure was achieved in 89.4%, with the best results in the ITU (100%), followed by STI (80%) and 70% in IAI. The 85% of the strains had minimum inhibitory concentrations (MIC) ≤8 μg/ml and 70% with MIC ≤4 μg/mL, however the rate of failure were high in intra-abdominal infections with high inocula or not controlled; CTX-M-15 was found in the 62.5%.. Piperacillin/tazobactam was efficient to obtain clinical and microbiological cure in patients with infections caused by ESBL producers but susceptible E. coli, especially in UTI and STI and to a lesser extent in IAI.

Topics: Adult; Aged; Anti-Bacterial Agents; beta-Lactamases; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Female; Humans; Male; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Treatment Outcome

Topics: Anti-Bacterial Agents; beta-Lactamases; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Humans; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination

Extended-spectrum β-lactamase-producing Escherichia coli (ESBL-Ec) is a frequent cause of acute pyelonephritis (APN), requiring carbapenem therapy. However, alternatives to carbapenems are needed due to the emergence of carbapenemase-producing micro-organisms. The purpose of this study was to compare the clinical efficacy of piperacillin/tazobactam (TZP) versus ertapenem in the treatment of adult patients with APN caused by ESBL-Ec. A retrospective observational study of APN caused by ESBL-Ec susceptible to TZP was performed at a university-affiliated hospital in the Republic of Korea between February 2011 and June 2013. All adult patients initially treated with in vitro-active TZP were compared with those treated with ertapenem to evaluate antibiotic clinical efficacy. The primary endpoint was treatment failure, defined as a composite of in-hospital mortality, change of initial antibiotic regimen and microbiological eradication failure. During the study period, 68 patients prescribed TZP and 82 patients prescribed ertapenem were eligible for inclusion in the study. There was no significant difference between the two treatment groups in the occurrence of in-hospital mortality, change of initial antibiotic regimen or microbiological eradication failure. In the multivariate analyses, predictors associated with treatment failure included septic shock [odds ratio (OR) = 4.27, 95% confidence interval (CI) 1.66-10.99] and recent administration of immunosuppressive agents (OR = 2.84, 95% CI 1.02-7.91). However, the type of antibiotic was not associated with treatment failure. TZP could be an effective alternative to ertapenem for the treatment of APN caused by ESBL-Ec, sparing carbapenem consumption in the multidrug-resistant era.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactamase Inhibitors; beta-Lactamases; beta-Lactams; Ertapenem; Escherichia coli; Escherichia coli Infections; Female; Hospitals, University; Humans; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pyelonephritis; Republic of Korea; Retrospective Studies; Survival Analysis; Treatment Failure; Young Adult

The emergence of resistant Escherichia coli to fluoroquinolones (FQs) is of growing concern, yet the latest guidelines for the treatment of pyelonephritis still recommend FQs as first-line treatment. Our primary objective was to determine the impact of discordant prescribing of FQs in E coli pyelonephritis on hospital length of stay (LOS) and early clinical response (ECR).. We retrospectively compared discordant and concordant prescribing of FQs for LOS and ECR. We also compared FQs, ceftriaxone, piperacillin/tazobactam, and carbapenems for these clinical outcomes.. Forty-nine patients included in the comparison between discordant (n = 9) and concordant (n = 40) prescribing of FQs. There was significantly lower ECR in patients with discordant prescribing of FQs (38 of 40, 95% vs 5 of 9, 55.6%, P = .0074) and a trend toward longer LOS (4 [2.3] days vs 3 [2.0] days, P = .0571). Illness severity, estimated using Simplified Acute Physiology Score (SAPS II) score, was similar between groups (P = .717).. There was a significantly decreased ECR and a trend toward increased LOS when FQs were used in FQ-resistant E coli. Regarding alternative treatment for E coli pyelonephritis, ceftriaxone was as effective as concordant FQs and significantly better than discordant FQs.

Topics: Adult; Anti-Bacterial Agents; Carbapenems; Ceftriaxone; Drug Resistance, Bacterial; Escherichia coli Infections; Female; Fluoroquinolones; Guidelines as Topic; Humans; Length of Stay; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pyelonephritis; Retrospective Studies; Treatment Outcome

Sub-inhibitory concentrations of antibiotics are always generated as a consequence of antimicrobial therapy and the effects of such residual products in bacterial morphology are well documented, especially the filamentation generated by beta-lactams. The aim of this study was to investigate some morphological and pathological aspects (virulence factors) of Escherichia coli cultivated under half-minimum inhibitory concentration (1.0 µg/mL) of piperacillin-tazobactam (PTZ sub-MIC). PTZ sub-MIC promoted noticeable changes in the bacterial cells which reach the peak of morphological alterations (filamentation) and complexity at 16 h of antimicrobial exposure. Thereafter the filamentous cells and a control one, not treated with PTZ, were comparatively tested for growth curve; biochemical profile; oxidative stress tolerance; biofilm production and cell hydrophobicity; motility and pathogenicity in vivo. PTZ sub-MIC attenuated the E. coli growth rate, but without changes in carbohydrate fermentation or in traditional biochemical tests. Overall, the treatment of E. coli with sub-MIC of PTZ generated filamentous forms which were accompanied by the inhibition of virulence factors such as the oxidative stress response, biofilm formation, cell surface hydrophobicity, and motility. These results are consistent with the reduced pathogenicity observed for the filamentous E. coli in the murine model of intra-abdominal infection. In other words, the treatment of E. coli with sub-MIC of PTZ suggests a decrease in their virulence.

Topics: Animals; Anti-Bacterial Agents; Biofilms; Disease Models, Animal; Escherichia coli; Escherichia coli Infections; Intraabdominal Infections; Locomotion; Metabolism; Mice; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Virulence

The prevalence of extended spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae in nursing home residents has rarely been reported in Taiwan.. A retrospective study was performed at medical wards of a district hospital at southern Taiwan between July 2009 and June 2011. Patients were included if they were older than 18 years, admitted via the emergency department, and their blood, sputum, or urine culture revealed the growth of Escherichia coli, Klebsiella pneumoniae, or Proteus mirabilis. From each patient only the first isolate from the infection site was included. Antimicrobial susceptibility was determined using the disc diffusion method.. Overall, 827 patients were included, with 354 (42.8%) coming from the community and 473 (57.2%) referred from a nursing home. Of the isolates acquired in nursing home, 45.5% (215/473) harbored ESBL. By contrast, 20.6% (73) of 354 isolates acquired in the community exhibited the ESBL production phenotype (p < 0.001). Of the isolates obtained from blood, urine, or sputum, 28.2% (37/131), 36.0% (208/578), or 36.4% (43/118) harbored ESBL, respectively, whereas 41% (211) of 515 E. coli isolates, 34.3% (72) of 210 K. pneumoniae, and 4.9% (5) of 102 P. mirabilis had ESBL. In general, the isolates from a nursing home or those with ESBL had lower antimicrobial susceptibility rates than those from the community or those without ESBL production. Only amikacin, piperacillin/tazobactam, ertapenem, and imipenem/meropenem were active against >90% Enterobacteriaceae isolates, irrespective of ESBL production.. ESBL production was common among clinical Enterobacteriaceae isolates, especially E. coli or those isolated from nursing home residents.

Topics: Amikacin; Anti-Bacterial Agents; beta-Lactamases; beta-Lactams; Blood; Drug Resistance, Multiple, Bacterial; Emergency Service, Hospital; Ertapenem; Escherichia coli; Escherichia coli Infections; Female; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Microbial Sensitivity Tests; Nursing Homes; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Proteus Infections; Proteus mirabilis; Retrospective Studies; Sputum; Taiwan; Thienamycins; Urine

Recent findings have identified Escherichia coli strains that are pan-β-lactam susceptible (PBL-S) but piperacillin-tazobactam resistant (TZP-R) in vitro We assessed the in vivo significance of this resistance profile in a neutropenic murine pneumonia model using humanized exposures of TZP with 18 clinical E. coli isolates, 8 TZP-S/PBL-S and 10 genotypically confirmed TZP-R/PBL-S. Despite phenotypically and genotypically defined resistance, TZP displayed efficacy against these isolates. Additional studies are required to define the clinical implications of these TZP-R/PBL-S strains.

Topics: Animals; Anti-Bacterial Agents; Cephalosporins; Colistin; Culture Media; Disease Models, Animal; Drug Administration Schedule; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Humans; Mice; Mice, Inbred ICR; Microbial Sensitivity Tests; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Tobramycin; Treatment Outcome

We report a case of a rare complication of acute appendicitis with perforation through the abdominal wall. The case points out that an intraabdominal origin should be considered in patients presenting with rapidly spreading soft tissue infections of the trunk.. A 58-year-old European woman presented to our hospital with a 1-week history of severe abdominal pain accompanied by rapidly spreading erythema and emphysema of the lower abdomen. On admission, the patient was in septic shock with leukocytosis and elevation of C-reactive protein. Among other diagnoses, necrotizing fasciitis was suspected. Computed tomography showed a large soft tissue infection with air-fluid levels spreading through the lower abdominal wall. During the operation, we found a perforated appendicitis breaking through the fascia and causing a rapidly progressive soft tissue infection of the abdominal wall. Appendicitis was the origin of the soft tissue infection. The abdominal wall was only secondarily involved.. Even though perforated appendicitis as an etiology of a rapidly progressive soft tissue infection of the abdominal wall is very rare, it should be considered in the differential diagnosis of abdominal wall cellulitis. The distinction between rapidly spreading subcutaneous infection with abscess formation and early onset of necrotizing fasciitis is often difficult and can be confirmed only by surgical intervention.

Topics: Abdominal Pain; Abdominal Wall; Anti-Bacterial Agents; Appendectomy; Appendicitis; Emphysema; Escherichia coli Infections; Female; Humans; Middle Aged; Penicillanic Acid; Peritonitis; Piperacillin; Piperacillin, Tazobactam Drug Combination; Reoperation; Soft Tissue Infections; Tomography, X-Ray Computed; Treatment Outcome

The relationship between fluoroquinolone resistance in Escherichia coli isolates causing nosocomial infection and hospital antibiotic consumption were investigated. Restriction of levofloxacin use was implemented to control the incidence of fluoroquinolone-resistant E coli in the hospital.. The study was conducted from January 2004 to December 2010. Antimicrobial agent consumption was obtained from the pharmacy computer system and presented as the defined daily doses per 1000 patient-days every 6 months. The incidence of fluoroquinolone-resistant E coli isolates causing nosocomial infections was obtained from the Department of Infection Control every 6 months. An antimicrobial stewardship program, restricting levofloxacain use, was implemented in July 2007.. The incidence of fluoroquinolone-resistant E coli causing nosocomial infections was significantly correlated with fluoroquinolone usage (p = 0.005), but not with the use of third- or fourth-generation cephalosporins, piperacillin-tazobactam, or carbapenems. Parenteral (p = 0.002), oral (p = 0.018), and total levofloxacin (p = 0.001) use were significantly correlated with the extent of fluoroquinolone resistance. With a reduction of levofloxacin use, a decrease of the incidence of fluoroquinolone resistance in E coli isolates was observed.. There is a significant correlation between levofloxacin use and the incidence of nosocomial fluoroquinolone-resistant E coli isolates. The incidence of fluoroquinolone-resistant E coli could be reduced by limiting levofloxacin consumption.

Topics: Anti-Bacterial Agents; Carbapenems; Cephalosporins; Cross Infection; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Humans; Levofloxacin; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination

This retrospective study was conducted to evaluate clinical outcomes of bacteremia caused by extended-spectrum β-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae and their antibiotic susceptibilities in febrile neutropenic children. Clinical characteristics, prognosis, and antibiotic susceptibilities were reviewed and compared between febrile neutropenic children with bacteremia caused by ESBL-producing and non-ESBL-producing E. coli and K. pneumoniae. A total of 61 episodes of E. coli and K. pneumoniae bacteremia, including 21 episodes (34.4%) due to ESBL-producing strains, were diagnosed. There was no significant factor associated with bacteremia by ESBL-producing strains. Empirical antibiotics were appropriate in 85.7% of the ESBL group and 95.0% of the non-ESBL group. In the entire study population, seven deaths (11.5%), including three deaths (4.9%) due to E. coli and K. pneumoniae bacteremia, occurred. The complication and mortality rates were not significantly different between the two groups. Antibiotic susceptibility rates were significantly lower in the ESBL group than in the non-ESBL group in most antibiotics. Although 52.4% and 66.7% of the ESBL-producing isolates were susceptible to piperacillin/tazobactam and cefepime, respectively, 96.7% of all the isolates and 90.5% of the ESBL-producing isolates were susceptible to piperacillin/tazobactam or cefepime in combination with aminoglycoside. In conclusion, the ESBL group did not show a significantly unfavorable outcome, and empirical therapy with piperacillin/tazobactam or cefepime in combination with aminoglycoside might be more useful for febrile neutropenic children, instead of β-lactam monotherapy in institutions with high prevalence of ESBL-producing E. coli and K. pneumoniae.

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Cefepime; Cephalosporins; Child; Escherichia coli; Escherichia coli Infections; Febrile Neutropenia; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies

The aim of the study was to identify risk factors associated with pre-transplant fecal carriage of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae in liver transplant recipients.. Over a 3-year period (January 2009-December 2011), 317 patients who underwent liver transplantation were screened preoperatively for fecal carriage of ESBL-producing Enterobacteriaceae. Risk factors for fecal carriage were investigated by univariate analysis and stepwise logistic regression.. Of the 317 patients screened, 50 (15.7%) harbored an ESBL-producing isolate. Previous infection with an ESBL-producing organism had developed during the last 6 months in 20% of fecal carriers versus in none of the non-carriers. Other variables associated with fecal carriage were a model for end-stage liver disease score ≥25, pre-transplant stay in the intensive care unit ≥48 h, hospital stay ≥10 days in the last 6 months, a history of spontaneous bacterial peritonitis (SBP), exposure to a β-lactam agent in the last month, and prophylaxis with norfloxacin. Independent predictors of fecal carriage in the multivariate logistic regression model were exposure to a β-lactam agent in the month preceding transplantation (odds ratio [OR] = 7.8, confidence interval [CI] = 4-15.5, P < 0.001), and a history of SBP (OR = 2.4, CI = 1.1-4.9, P = 0.02).. Previous infection with an ESBL-producing isolate, recent exposure to a β-lactam agent, and a history of SBP are risk factors for preoperative fecal carriage of ESBL-producing Enterobacteriaceae in liver transplant recipients. Patients at risk of fecal carriage should receive intraoperative prophylaxis and, when necessary, empiric postoperative antimicrobial treatment that includes coverage for these organisms.

Topics: Adult; Amikacin; beta-Lactamases; beta-Lactams; Cefoxitin; Ciprofloxacin; Drug Resistance, Bacterial; End Stage Liver Disease; Enterobacter cloacae; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli; Escherichia coli Infections; Feces; Female; Humans; Imipenem; Klebsiella; Klebsiella Infections; Klebsiella pneumoniae; Liver Transplantation; Logistic Models; Male; Microbial Sensitivity Tests; Middle Aged; Multivariate Analysis; Penicillanic Acid; Peritonitis; Piperacillin; Piperacillin, Tazobactam Drug Combination; Preoperative Period; Risk Factors; Severity of Illness Index

Avibactam is a novel non-β-lactam β-lactamase inhibitor that has been shown in vitro to inhibit class A, class C, and some class D β-lactamases. It is currently in phase 3 of clinical development in combination with ceftazidime. In this study, the efficacy of ceftazidime-avibactam was evaluated in a murine septicemia model against five ceftazidime-susceptible (MICs of 0.06 to 0.25 μg/ml) and 15 ceftazidime-resistant (MICs of 64 to >128 μg/ml) species of Enterobacteriaceae, bearing either TEM, SHV, CTX-M extended-spectrum, or AmpC β-lactamases. In the first part of the study, ceftazidime-avibactam was administered at ratios of 4:1 and 8:1 (wt/wt) to evaluate the optimal ratio for efficacy. Against ceftazidime-susceptible isolates of Klebsiella pneumoniae and Escherichia coli, ceftazidime and ceftazidime-avibactam demonstrated similar efficacies (50% effective doses [ED50] of <1.5 to 9 mg/kg of body weight), whereas against ceftazidime-resistant β-lactamase-producing strains (ceftazidime ED50 of >90 mg/kg), the addition of avibactam restored efficacy to ceftazidime (ED50 dropped to <5 to 65 mg/kg). In a subsequent study, eight isolates (two AmpC and six CTX-M producers) were studied in the septicemia model. Ceftazidime-avibactam was administered at a 4:1 (wt/wt) ratio, and the efficacy was compared to that of the 4:1 (wt/wt) ratio of either piperacillin-tazobactam or cefotaxime-avibactam. Against the eight isolates, ceftazidime-avibactam was the more effective combination, with ED50 values ranging from 2 to 27 mg/kg compared to >90 mg/kg and 14 to >90 mg/kg for piperacillin-tazobactam and cefotaxime-avibactam, respectively. This study demonstrates that the potent in vitro activity observed with the ceftazidime-avibactam combination against ceftazidime-resistant Enterobacteriaceae species bearing class A and class C β-lactamases translated into good efficacy in the mouse septicemia model.

Topics: Animals; Anti-Bacterial Agents; Azabicyclo Compounds; Bacterial Proteins; beta-Lactamase Inhibitors; beta-Lactamases; Ceftazidime; Drug Combinations; Escherichia coli; Escherichia coli Infections; Klebsiella Infections; Klebsiella pneumoniae; Male; Mice; Mice, Inbred ICR; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sepsis

Escherichia coli is commonly involved in infections with a heavy bacterial burden. Piperacillin-tazobactam and carbapenems are among the recommended empirical treatments for health care-associated complicated intra-abdominal infections. In contrast to amoxicillin-clavulanate, both have reduced in vitro activity in the presence of high concentrations of extended-spectrum β-lactamase (ESBL)-producing and non-ESBL-producing E. coli bacteria. Our goal was to compare the efficacy of these antimicrobials against different concentrations of two clinical E. coli strains, one an ESBL-producer and the other a non-ESBL-producer, in a murine sepsis model. An experimental sepsis model {~5.5 log10 CFU/g [low inoculum concentration (LI)] or ~7.5 log(10) CFU/g [high inoculum concentration (HI)]} using E. coli strains ATCC 25922 (non-ESBL producer) and Ec1062 (CTX-M-14 producer), which are susceptible to the three antimicrobials, was used. Amoxicillin-clavulanate (50/12.5 mg/kg given intramuscularly [i.m.]), piperacillin-tazobactam (25/3.125 mg/kg given intraperitoneally [i.p.]), and imipenem (30 mg/kg i.m.) were used. Piperacillin-tazobactam and imipenem reduced spleen ATCC 25922 strain concentrations (-2.53 and -2.14 log10 CFU/g [P < 0.05, respectively]) in the HI versus LI groups, while amoxicillin-clavulanate maintained its efficacy (-1.01 log10 CFU/g [no statistically significant difference]). Regarding the Ec1062 strain, the antimicrobials showed lower efficacy in the HI than in the LI groups: -0.73, -1.89, and -1.62 log10 CFU/g (P < 0.05, for piperacillin-tazobactam, imipenem, and amoxicillin-clavulanate, respectively, although imipenem and amoxicillin-clavulanate were more efficacious than piperacillin-tazobactam). An adapted imipenem treatment (based on the time for which the serum drug concentration remained above the MIC obtained with a HI of the ATCC 25922 strain) improved its efficacy to -1.67 log10 CFU/g (P < 0.05). These results suggest that amoxicillin-clavulanate could be an alternative to imipenem treatment of infections caused by ESBL- and non-ESBL-producing E. coli strains in patients with therapeutic failure with piperacillin-tazobactam.

Topics: Amoxicillin-Potassium Clavulanate Combination; Animals; Anti-Bacterial Agents; beta-Lactamases; Colony Count, Microbial; Escherichia coli; Escherichia coli Infections; Female; Imipenem; Injections, Intramuscular; Injections, Intraperitoneal; Intraabdominal Infections; Mice; Mice, Inbred C57BL; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sepsis; Treatment Outcome

We investigated the impact of the piperacillin-tazobactam MIC in the outcome of 39 bloodstream infections due to extended-spectrum-β-lactamase-producing Escherichia coli. All 11 patients with urinary tract infections survived, irrespective of the MIC. For other sources, 30-day mortality was lower for isolates with a MIC of ≤ 2 mg/liter than for isolates with a higher MIC (0% versus 41.1%; P = 0.02).

Topics: Aged; Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Cohort Studies; Drug Therapy, Combination; Enzyme Inhibitors; Escherichia coli; Escherichia coli Infections; Humans; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Tazobactam; Treatment Outcome; Urinary Tract Infections

Diabetic foot ulcer (DFU) is a common and devastating complication in diabetes. Antimicrobial resistance mediated by extended-spectrum β-lactamases (ESBLs) production by bacteria is considered to be a major threat for foot amputation. The present study deals with the detection of Escherichia coli and the prevalence of bla(TEM), bla(SHV) and bla(OXA) genes directly from biopsy and swab of foot ulcers of diabetic patients. In total, 116 DFU patients were screened, of which 42 suffering with severe DFUs were selected for this study. Altogether 16 E. coli strains were successfully isolated from biopsy and/or swab samples of 15 (35.71%) patients. ESBL production was noted in 12 (75%) strains. Amplification of β-lactamase genes by multiplex PCR showed the presence of bla(CTX-M) like genes in 10 strains, bla(TEM) and bla(OXA) in 9 strains each, and bla(SHV) in 8 of the total 16 strains of E. coli. Out of the ten antibiotics tested, E. coli strains were found to be resistant to ampicillin (75%), cefoxitin (56.25%), cefazolin (50%), meropenem (37.5%), cefoperazone (25%), cefepime (31.25%), ceftazidime (56.25%), and cefotaxime (68.75%) but all showed sensitivity (100%) to clindamycin and piperacillin-tazobactam. 3D models of the most prevalent variants of β-lactamases namely TEM-1, SHV-1, OXA-1, and ESBL namely CTX-M-15 were predicted and docking was performed with clindamycin and piperacillin-tazobactam to reveal the molecular basis of drug sensitivity. Docking showed the best docking score with significant interactions, forming hydrogen bond, Van der Waals and polar level interaction with active site residues. Findings of the present study may provide useful insights for the development of new antibiotic drugs and may also prevent ESBLs-mediated resistance problem in DFU. The novel multiplex PCR assay designed in this study may be routinely used in clinical diagnostics of E. coli and associated bla(TEM), bla(SHV), and bla(OXA) like genes.

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamase Inhibitors; beta-Lactamases; beta-Lactams; Clindamycin; Diabetic Foot; Escherichia coli; Escherichia coli Infections; Gene Expression; Humans; Microbial Sensitivity Tests; Molecular Docking Simulation; Multiplex Polymerase Chain Reaction; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Structural Homology, Protein; Structure-Activity Relationship

Topics: Animals; Anti-Bacterial Agents; beta-Lactamases; Disease Models, Animal; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Humans; Mice; Microbial Sensitivity Tests; Nociceptive Pain; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Staphylococcal Infections

Preventing the dissemination of antimicrobial resistance depends on appropriate antibiotic stewardship and accurate antimicrobial susceptibility testing (AST). We report the international dissemination of Escherichia coli strains, showing discrepancies between reference methods when phenotypically tested for susceptibility to piperacillin/tazobactam (TZP). We demonstrate that these related strains are predisposed to problematic TZP AST interpretations.

Topics: Anti-Bacterial Agents; Cluster Analysis; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Humans; Microbial Sensitivity Tests; Penicillanic Acid; Phenotype; Piperacillin; Piperacillin, Tazobactam Drug Combination; Reference Standards; Reproducibility of Results

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Bacteremia; beta-Lactamase Inhibitors; Escherichia coli Infections; Female; Humans; Male; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination

Extended-spectrum ß-lactamase-producing Escherichia coli (ESBL-EC) is an important cause of invasive infections. Alternatives to carbapenems--considered the drugs of choice--are needed because of the emergence of carbapenemase-producing enterobacteria. The efficacy of ß-lactam/ß-lactam inhibitors (BLBLI) in such infections is controversial.. The authors performed a post hoc analysis of patients with bloodstream infections due to ESBL-EC from 6 published prospective cohorts. Mortality and length of hospital stay in patients treated with an active BLBLI (amoxicillin-clavulanic acid [AMC] and piperacillin-tazobactam [PTZ]) or carbapenem were compared in 2 cohorts: the empirical therapy cohort (ETC) and the definitive therapy cohort (DTC). Confounding was controlled by multivariate analysis; for patients in the ETC, a propensity score for receiving carbapenem was also used.. The ETC included 103 patients (BLBLI, 72; carbapenem, 31), and the DTC included 174 (BLBLI, 54; carbapenem, 120). Mortality rates at day 30 for those treated with BLBLI versus carbapenems were 9.7% versus 19.4% for the ETC and 9.3% versus 16.7% for the DTC, respectively (P > .2, log-rank test). After adjustment for confounders, no association was found between either empirical therapy with BLBLI (adjusted hazard ratio [HR], 1.14; 95% confidence interval [CI], .29-4.40; P = .84) or definitive therapy (adjusted HR, 0.76; 95% CI, .28-2.07; P = .5) and increased mortality. Furthermore, BLBLI therapy, with respect to carbapenem, was not found to influence length of hospital stay.. These results suggest that AMC and PTZ are suitable alternatives to carbapenems for treating patients with bloodstream infections due to ESBL-EC if active in vitro and would be particularly useful as definitive therapy.

Topics: Aged; Aged, 80 and over; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Bacteremia; beta-Lactam Resistance; beta-Lactamase Inhibitors; Escherichia coli; Escherichia coli Infections; Female; Humans; Male; Middle Aged; Multivariate Analysis; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Proportional Hazards Models; Prospective Studies; Spain

CXA-101 is a novel antipseudomonal cephalosporin with enhanced activity against Gram-negative organisms displaying various resistance mechanisms. This study evaluates the efficacy of exposures approximating human percent free time above the MIC (%fT > MIC) of CXA-101 with or without tazobactam and piperacillin-tazobactam (TZP) against target Gram-negative organisms, including those expressing extended-spectrum β-lactamases (ESBLs). Sixteen clinical Gram-negative isolates (6 Pseudomonas aeruginosa isolates [piperacillin-tazobactam MIC range, 8 to 64 μg/ml], 4 Escherichia coli isolates (2 ESBL and 2 non-ESBL expressing), and 4 Klebsiella pneumoniae isolates (3 ESBL and 1 non-ESBL expressing) were used in an immunocompetent murine thigh infection model. After infection, groups of mice were administered doses of CXA-101 with or without tazobactam (2:1) designed to approximate the %fT > MIC observed in humans given 1 g of CXA-101 with or without tazobactam every 8 h as a 1-h infusion. As a comparison, groups of mice were administered piperacillin-tazobactam doses designed to approximate the %fT > MIC observed in humans given 4.5 g piperacillin-tazobactam every 6 h as a 30-min infusion. Predicted piperacillin-tazobactam %fT > MIC exposures of greater than 40% resulted in static to >1 log decreases in CFU in non-ESBL-expressing organisms with MICs of ≤32 μg/ml after 24 h of therapy. Predicted CXA-101 with or without tazobactam %fT > MIC exposures of ≥37.5% resulted in 1- to 3-log-unit decreases in CFU in non-ESBL-expressing organisms, with MICs of ≤16 μg/ml after 24 h of therapy. With regard to the ESBL-expressing organisms, the inhibitor combinations showed enhanced CFU decreases versus CXA-101 alone. Due to enhanced in vitro potency and resultant increased in vivo exposure, CXA-101 produced statistically significant reductions in CFU in 9 isolates compared with piperacillin-tazobactam. The addition of tazobactam to CXA-101 produced significant reductions in CFU for 7 isolates compared with piperacillin-tazobactam. Overall, human simulated exposures of CXA-101 with or without tazobactam demonstrated improved efficacy versus piperacillin-tazobactam.

Topics: Animals; Anti-Bacterial Agents; beta-Lactamases; Cephalosporins; Colony Count, Microbial; Disease Models, Animal; Drug Combinations; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Mice; Mice, Inbred ICR; Microbial Sensitivity Tests; Penicillanic Acid; Phenotype; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pseudomonas aeruginosa; Pseudomonas Infections; Tazobactam; Thigh

High-level expression of AmpC β-lactamase genes is associated with increased resistance to β-lactam antibiotics. bla(CMY-2) is the most prevalent plasmid-encoded AmpC gene found in Escherichia coli worldwide, and the gene is often found on plasmids of the IncI1 replicon type. Replication of IncI1 plasmids is controlled by antisense RNA transcribed from the gene inc, and nucleotide changes in the hairpin loop region of inc have been associated with increased plasmid copy number of IncI1 mini-plasmid constructs. The objective of this study was to determine the mechanism(s) responsible for increased bla(CMY-2) expression in three piperacillin/tazobactam-selected E. coli mutant strains with bla(CMY-2) encoded on a 100 kb IncI1 plasmid.. Mutants were selected from a clinical E. coli strain by exposure to superinhibitory concentrations of piperacillin/tazobactam. β-Lactam susceptibilities were measured by agar dilution. Relative bla(CMY-2) transcript levels, gene copy number and IncI1 plasmid copy number were measured by real-time PCR. The inc gene of all strains was sequenced.. Piperacillin/tazobactam MICs were 16- to 128-fold higher for mutant strains than for their parent strain. This increase in MICs correlated with 3- to 13-fold increases in bla(CMY-2) gene expression, bla(CMY-2) copy number and IncI1 plasmid copy number. Two mutants with 8- and 13-fold increases in IncI1 copy number had single point mutations located within the hairpin loop region of inc.. These findings demonstrate that inc point mutations can be associated with increased copy number of a 100 kb IncI1 plasmid, and lead to increased bla(CMY-2) expression and piperacillin/tazobactam resistance.

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; DNA Replication; Escherichia coli; Escherichia coli Infections; Gene Dosage; Humans; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Plasmids; Point Mutation; RNA, Antisense

Spontaneous bacterial peritonitis is a common infection in cirrhosis, associated with a high mortality. Third-generation cephalosporins are recommended as first-line treatment. The aim was to evaluate the epidemiology of microbiological ascitic fluid findings and antimicrobial resistance in Denmark.. All patients with cirrhosis and a positive ascitic fluid culture, at three university hospitals in the Copenhagen area during a 7-year period, were retrospectively evaluated. Patients with apparent secondary peritonitis were excluded from the study.. One hundred and forty cases with 187 microbiological isolates were identified. The findings were: Gram-positive cocci, n = 86 (45.9%); Enterobacteriaceae, n = 59 (31.7%), with Escherichia coli identified in 31 cases; anaerobes, n = 14 (7.5%); yeast, n = 12 (6.4%); and cutaneous flora, n = 15 (8.0%). One case of Listeria monocytogenes was identified (0.5%). Overall antibiotic coverage was 57% for cephalosporins, 73% for piperacillin-tazobactam, and 72% for meropenem. Mortality rates in patients with isolates susceptible or resistant to the initial antibiotic treatment at 30 days follow-up were 35% and 55%, respectively (p = 0.017, Log-rank test).. Almost half of the isolates were Gram-positive cocci, and as the overall antibiotic coverage with a cephalosporin was only 57%, and survival significantly dependent on whether the microbial etiology was susceptible to initial antibiotic treatment or not, a change of standard empiric antibiotic regime should be considered. Piperacillin-tazobactam could be a favorable choice.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Ascitic Fluid; Cephalosporins; Denmark; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Gram-Positive Bacterial Infections; Gram-Positive Cocci; Humans; Kaplan-Meier Estimate; Liver Cirrhosis; Male; Meropenem; Middle Aged; Mycoses; Penicillanic Acid; Peritonitis; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Thienamycins

Six years after initiating a monthly antibiotic cycling protocol in the surgical intensive care unit (SICU), we retrospectively reviewed antibiogram-derived sensitivities of predominant gram-negative pathogens before and after antibiotic cycling. We also examined susceptibility patterns in the medical intensive care unit (MICU) where antibiotic cycling is not practiced.. Antibiotic cycling protocol was implemented in the SICU starting in 2003, with monthly rotation of piperacillin/tazobactam, imipenem/cilastin, and ceftazidime. SICU antibiogram data from positive clinical cultures for years 2000 and 2002 were included in the pre-cycling period, and those from 2004 to 2009 in the cycling period.. Profiles of SICU pseudomonal isolates before (n = 116) and after (n = 205) implementing antibiotic cycling showed statistically significant improvements in susceptibility to ceftazidime (66% versus 81%; P = 0.003) and piperacillin/tazobactam (75% versus 85%; P = 0.021), while susceptibility to imipenem remained unaltered (70% in each case; P = 0.989). Susceptibility of E. coli isolates to piperacillin/tazobactam improved significantly (46% versus 83%; P < 0.0005), trend analysis showing this improvement to persist over the study period (P = 0.025). Similar findings were not observed in the MICU. Review of 2004-2009 antibiotic prescription practices showed monthly heterogeneity in the SICU, and a 2-fold higher prescribing of piperacillin/tazobactam in the MICU (P < 0.0001).. Six years into antibiotic cycling, we found either steady or improved susceptibilities of clinically relevant gram-negative organisms in the SICU. How much of this effect is from cycling is unknown, but the antibiotic heterogeneity provided by this practice justifies its ongoing use.

Topics: Anti-Bacterial Agents; Ceftazidime; Cilastatin; Cilastatin, Imipenem Drug Combination; Critical Care; Cross Infection; Drug Combinations; Drug Resistance, Bacterial; Enterobacter cloacae; Enterobacteriaceae Infections; Escherichia coli; Escherichia coli Infections; Humans; Imipenem; Infection Control; Klebsiella Infections; Klebsiella pneumoniae; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Surgical Wound Infection

We investigated the bacteriostatic and bactericidal activities of piperacillin/tazobactam against 16 clinical Escherichia coli producing inhibitor-resistant TEM β-lactamases (IRT; 13/16) and complex mutant TEM enzymes (CMT; 3/16).. Bacteriostatic activity was evaluated by three methods (disc diffusion, Vitek2 automated system, MIC determination by a microdilution method) and a time-killing study was used to investigate the bactericidal effect against standard (5 × 10(5) cfu/mL) and high inocula (5 × 10(6) cfu/mL).. Piperacillin/tazobactam was bacteriostatic against most of the tested strains (15/16). Using a high inoculum, the piperacillin/tazobactam combination was not bactericidal against the 13 IRT-producing strains and one of the CMT-producing strains (1/3). A loss of bactericidal activity was still observed for seven IRT-producing strains (7/13) with a standard bacterial inoculum (<99.9% killing over 24 h).. Despite usual in vitro bacteriostatic activity, the piperacillin/tazobactam combination was not bactericidal against most IRT-producing clinical strains of E. coli, especially for the treatment of a high bacterial inoculum. This possible loss of bactericidal effect should be brought to the attention of physicians and may require high dosing regimens for the treatment of severe infections.

Topics: Anti-Bacterial Agents; beta-Lactamases; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Humans; Microbial Sensitivity Tests; Microbial Viability; Mutant Proteins; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination

A significant inoculum-size effect has been observed with piperacillin-tazobactam, and has been associated with beta-lactamase production in extended-spectrum beta-lactamase (ESBL) producers. This association has not been previously studied in the case of amoxycillin-clavulanate. Piperacillin-tazobactam and amoxycillin-clavulanate were compared, using high inocula of susceptible strains either harbouring ESBLs or not. Two non-ESBL-producing and 15 amoxycillin-clavulanate-susceptible and piperacillin-tazobactam-susceptible ESBL-producing Escherichia coli isolates, and their respective transconjugants, were tested in dilution susceptibility tests using standard and 100-fold higher inocula. Three ESBL-producing strains and E. coli ATCC 25922 were selected for time-kill studies using standard and high initial inocula. At high inocula, MICs of piperacillin increased >eight-fold for non-ESBL-producing strains, and MICs of piperacillin-tazobactam (8:1 ratio or with tazobactam fixed at 4 mg/L) increased>eight-fold for all ESBL-producing strains. However, amoxycillin MICs were not affected by a high inoculum with non-ESBL-producing strains, whereas the MICs of amoxycillin-clavulanate (2:1 and 4:1) increased

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; beta-Lactamases; Colony Count, Microbial; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Humans; Microbial Sensitivity Tests; Microbial Viability; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Time Factors

Topics: Abdominal Abscess; Albendazole; Animals; Anthelmintics; Anti-HIV Agents; Appendectomy; Appendicitis; Ascariasis; Ascaris lumbricoides; Bacteroides fragilis; Bacteroides Infections; Combined Modality Therapy; Emigrants and Immigrants; Escherichia coli Infections; Female; HIV Infections; Humans; Immunocompromised Host; Intestinal Diseases, Parasitic; Jejunum; Paraguay; Penicillanic Acid; Peritonitis; Piperacillin; Piperacillin, Tazobactam Drug Combination; Young Adult

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

Topics: Anti-Bacterial Agents; beta-Lactamases; Cefepime; Cephalosporins; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Hospitals, Urban; Humans; India; Intensive Care Units; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sepsis; Thienamycins

Topics: Animals; Anti-Bacterial Agents; Ascitic Fluid; Bacteroides fragilis; Bacteroides Infections; beta-Lactams; Blood; Colony Count, Microbial; Ertapenem; Escherichia coli; Escherichia coli Infections; Female; Mice; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sepsis

To investigate the role of replacement of third-generation cephalosporins by piperacillin-tazobactam (pip-tazo) in influencing the colonization of extended-spectrum beta-lactamases (ESBLs)-producing Escherichia coli (E. coli) in intestinal tract.. The study was divided into two phases lasting altogether 9 months, namely the pre-replacement phase (phase I, 3 months) and replacement phase (phase II, 6 months). In the latter phase, third-generation cephalosporins was restricted and replaced by pip-tazo. In phase I and phase IIb (the last 3 months of phase II), clinical data and rectal swab were taken for E. coli isolation as follow: within 24 hrs after admission (baseline screening), every week and 48 hrs before discharge. ESBLs production was detected with double disc test. Acquisition rate of ESBLs-producing E. coli were calculated both in ES1 group (patients' rectal swab collected and tests at least 2 times) and ES2 group (ES1 but with negative ESBLs either at the time of screening on admission or at anytime during the hospital stay). Continuous variable was compared using unpaired t-test and categorical variables was compared using Pearson Chi square test. Fisher's exact test was used in the two phases.. In phase IIb, as compared with in phase I, the total consumption of antibiotics other than pip-tazo was reduced by 38.40%, the third-generation cephalosporins consumption was reduced by 70.11%, but pip-tazo consumption was raised by 895.35%. Meanwhile, the acquisition rate of ESBLs-producing E. coli in rectal swab was significantly decreased in phase IIb as compared with phase I (11.4% vs 24.0%) in ES1 group and the same is true in ES2 group (11.8% vs 27.9%).. Replacement of third-generation cephalosporin with pip-tazo can reduce colonization of ESBLs--producing E. coli in intestinal tract.

Topics: Adult; Aged; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; Cephalosporins; Escherichia coli; Escherichia coli Infections; Female; Humans; Intestines; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies

Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli, particularly those producing CTX-M types of ESBL, are emerging pathogens. Bacteremia caused by these organisms represents a clinical challenge, because the organisms are frequently resistant to the antimicrobials recommended for treatment of patients with suspected E. coli sepsis.. A cohort study was performed that included all episodes of bloodstream infection due to ESBL-producing E. coli during the period from January 2001 through March 2005. Data on predisposing factors, clinical presentation, and outcome were collected. ESBLs were characterized using isoelectric focusing, polymerase chain reaction, and sequencing.. Forty-three episodes (8.8% of cases of bacteremia due to E. coli) were included; 70% of the isolates produced a CTX-M type of ESBL. The most frequent origins of infection were the urinary (46%) and biliary tracts (21%). Acquisition was nosocomial in 21 cases (49%), health care associated in 14 cases (32%), and strictly community acquired in 8 cases (19%). Thirty-eight percent and 25% of patients had obstructive diseases of the urinary and biliary tracts, respectively, and 38% had recently received antimicrobials. Nine patients (21%) died. Compared with beta-lactam/beta-lactamase-inhibitor and carbapenem-based regimens, empirical therapy with cephalosporins or fluoroquinolones was associated with a higher mortality rate (9% vs. 35%; P=.05) and needed to be changed more frequently (24% vs. 78%; P=.001).. ESBL-producing E. coli is a significant cause of bloodstream infection in hospitalized and nonhospitalized patients in the context of the emergence of CTX-M enzymes. Empirical treatment of sepsis potentially caused by E. coli may need to be reconsidered in areas where such ESBL-producing isolates are present.

Topics: Adult; Aged; Aged, 80 and over; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Cephalosporins; Cohort Studies; Community-Acquired Infections; Cross Infection; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Fluoroquinolones; Humans; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination

With the overuse of expanded-spectrum cephalosporins, especially ceftazidime, outbreaks of extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae and Escherichia coli infections have been reported. In this prospective observational study, we demonstrated that the addition of piperacillin/tazobactam to the formulary and the restriction of ceftazidime were associated with a decrease in the percentage of ceftazidime-resistant isolates. When the use of ceftazidime decreased by 96.43%, and the use of piperacillin/tazobactam increased by over 50% during the 9-month study period, a concomitant decrease was found in the percentage of colonization and infection by ESBL-producing E. coli or K. pneumoniae in patients admitted to the intensive care unit. Results from this 9-month intervention study support the concept that levels of local and institutional use of ceftazidime are of substantial importance to the emergence and persistence of endemic ceftazidime-resistant K. pneumoniae.

Topics: Anti-Bacterial Agents; beta-Lactamases; Ceftazidime; Cephalosporin Resistance; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Taiwan