piperacillin--tazobactam-drug-combination and Enterobacteriaceae-Infections

The continuous rise in infections caused by third-generation cephalosporin-resistant Enterobacterales (e.g. extended-spectrum beta-lactamase- or AmpC-producing Enterobacterales ) is a major health concern. Carbapenems are regarded as the antibiotics of choice for the treatment of these infections. However, their indiscriminant use is not without consequences, and has contributed to the emergence of carbapenem-resistant Enterobacterales .In this review, we discuss the available evidence supporting the use of other betalactams, nonbetalactams and the new betalactams/beta-lactamase inhibitors (BLA/BLI) to treat these infections. We also analyze unresolved issues in this field.. Piperacillin tazobactam (PTZ) was classically recommended as a carbapenem-sparing agent. However, data have emerged against its use and it is now a controversial recommendation. IDSA, European and British guidelines reject the empirical use of PTZ for these pathogens, reserving its use for rare clinical situations.Other issues that continue to generate debate are the use of extended infusion (3 h) PTZ, the use of older antibiotics, a shortened course of carbapenems and reserving the new BLA/BLI for these infections.. New treatment strategies should be based on clinical evidence, local epidemiology and the microbiological activity of these drugs.

Topics: Anti-Bacterial Agents; beta-Lactamase Inhibitors; beta-Lactamases; Carbapenems; Enterobacteriaceae Infections; Humans; Microbial Sensitivity Tests; Piperacillin, Tazobactam Drug Combination

Topics: Age Factors; Aged, 80 and over; Anti-Bacterial Agents; Cholecystitis, Acute; Disseminated Intravascular Coagulation; Drug Substitution; Edwardsiella tarda; Enterobacteriaceae Infections; Female; Humans; Piperacillin, Tazobactam Drug Combination; Sepsis; Treatment Outcome

The widespread diffusion of extended-spectrum β-lactamases (ESBLs)-producing Enterobacteriales currently represents a major threat for public health worldwide. Carbapenems are currently considered the first-line choice for serious ESBL infections. However, the dramatic global increase in ESBL prevalence has led to a significant overuse of carbapenems that has promoted the selection and spread of carbapenemases, which might further prejudicated our ability to treat infections due to multidrug-resistant pathogens. Therefore, strategies to limit the use of carbapenems should be implemented.. Although piperacillin-tazobactam should no longer be considered an alternative to carbapenems for definitive treatment of bloodstream infections due to ESBL-producing strains, it might still represent an alternative for step-down therapy or for low-to-moderate severity infection originating from urinary or biliary sources and when piperacillin-tazobactam minimum inhibitory concentration of 4 mg/l or less. Ceftazidime-avibactam and ceftolozane-tazobactam are both carbapenem sparing agents that appear interesting alternatives for treatment of serious ESBL infections. New β-lactams/β-lactamase inhibitors (BL/BLI), including cefepime-enmetazobactam, ceftaroline fosamil-avibactam, aztreonam-avibactam and cefepime-zidebactam, are also promising agents for treatment of ESBL infections, but further clinical data are needed to establish their efficacy relative to carbapenems. The role of carbapenems/β-lactamase inhibitors remain to be clarified.. New BL/BLI have distinctive specificities and limitations that require further investigations. Future randomized clinical trials are required to define the best strategy for their administering for ESBL infections.

Topics: Anti-Bacterial Agents; Azabicyclo Compounds; Bacterial Proteins; beta-Lactamase Inhibitors; beta-Lactamases; beta-Lactams; Carbapenems; Ceftaroline; Ceftazidime; Cephalosporins; Cyclooctanes; Drug Combinations; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Microbial Sensitivity Tests; Piperacillin, Tazobactam Drug Combination; Public Health; Sepsis; Tazobactam

A late preterm male infant of 36 weeks gestation and a birth weight of 2100 g was admitted on day 35 of life with complaints of respiratory distress and lethargy. He was diagnosed as a case of sepsis screen positive culture negative sepsis and was managed with respiratory support and intravenous antibiotics for 10 days. The infant improved clinically and was on spoon feeds by day 14 of admission. On day 14 of admission, he developed new-onset respiratory distress and was diagnosed as a case of nosocomial pneumonia based on chest radiography findings. The blood culture grew a rare organism

Topics: Anti-Bacterial Agents; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Infant; Lethargy; Male; Piperacillin, Tazobactam Drug Combination; Respiration, Artificial; Respiratory Distress Syndrome, Newborn; Sepsis; Spinal Puncture; Treatment Outcome

The continued rise in infections caused by extended-spectrum β-lactamase (ESBL)-producing pathogens is recognized globally as one of the most pressing concerns facing the healthcare community. Carbapenems are widely regarded as the antibiotics of choice for the treatment of ESBL-producing infections, even when in vitro activity to other β-lactams has been demonstrated. However, indiscriminant carbapenem use is not without consequence, and carbapenem overuse has contributed to the emergence of carbapenem-resistant Enterobacteriaceae. The use of non-carbapenem β-lactams for the treatment of ESBL infections has yielded conflicting results. In this review, we discuss the available data for the use of cephamycins, cefepime, piperacillin-tazobactam, ceftolozane-tazobactam, and ceftazidime-avibactam for the treatment of ESBL infections.

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamase Inhibitors; beta-Lactamases; Cefepime; Cephalosporins; Cephamycins; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Treatment Outcome

Extended spectrum β-lactamases (ESBL) and AmpC β-lactamases are increasing causes of resistance in many Gram-negative pathogens of common infections. This has led to a growing utilization of broad spectrum antibiotics, most predominately the carbapenem agents. As the prevalence of ESBL and AmpC-producing isolates and carbapenem resistance has increased, interest in effective alternatives for the management of these infections has also developed.. This article summarizes clinical literature evaluating the utility of carbapenem-sparing regimens for the treatment of ESBL and AmpC-producing Enterobacteriaceae, mainly β-lactam-β-lactamase inhibitor combinations and cefepime (FEP).. Based on available data, the use of piperacillin-tazobactam (PTZ) and FEP in the treatment of ESBL-producing Enterobacteriaceae cannot be widely recommended. However, certain infections and patient characteristics may support for effective use of these alternative agents. In the treatment of infections caused by AmpC-producing Enterobacteriaceae, FEP has been shown to be a clinically useful carbapenem-sparing alternative. Carbapenems and FEP share many structurally similar characteristics in regards to susceptibility to AmpC β-lactamases, which further create confidence in the use FEP in these situations. Patient and infection specific characteristics should be used to employ FEP optimally.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamase Inhibitors; beta-Lactamases; beta-Lactams; Cefepime; Cephalosporins; Drug Resistance, Bacterial; Drug Therapy, Combination; Enterobacteriaceae; Enterobacteriaceae Infections; Gram-Negative Aerobic Bacteria; Gram-Negative Bacterial Infections; Humans; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination

Therapy of infections caused by extended-spectrum beta-lactamase (ESBL)-producing bacteria with an antimicrobial to which they are resistant results in treatment failure, higher cost and increased mortality. The CLSI recommends reporting ESBL-producing strains of Escherichia coli, Klebsiella spp. and Proteus spp. as resistant to all penicillin, true cephalosporin and monobactam antimicrobials, but as susceptible to beta-lactam-beta-lactamase inhibitor combinations, including piperacillin-tazobactam, when they test as such. Current literature supports the action of piperacillin-tazobactam against susceptible strains of ESBL-producing bacteria based on the structure-activity relationship between inhibitors and the ESBLs, as well as on recent clinical outcome studies.

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamase Inhibitors; beta-Lactamases; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli; Klebsiella; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Practice Patterns, Physicians'; Treatment Outcome

A predictive parameter of beta-lactam therapeutic efficacy is the time (T > MIC) while antibiotic serum concentrations are above the MIC of suspected bacteriological agents. This led us to carry out a randomised open study to compare the usually used intermittent administration of Tazocin (three injections of 4 g/0.5 g a day) and continuous perfusion of 12 g/1.5 g a day by calculating these T > MIC. Patients from digestive reanimation department were randomised within two arms: continuous or intermittent administration. Sixteen takings of blood were executed over a forty-hour period. After liquid/liquid extraction, piperacillin and tazobactam serum concentrations were determined by HPLC with a reversed phase column (C18) and a UV spectrophotometry detection. Then, from the time-concentration curves we have evaluated the T > MIC for an enterobacteria (MIC = 8 micrograms/mL) and for Pseudomonas (MIC = 16 micrograms/mL). Concerning intermittent administration T > MIC were 74% (c > MICenterobacteria) and 62% (c > MICPseudomonas). These percentages in the continuous arm were 100% (c > MICenterobacteria) and 99% (c > MICPseudomonas). Tazobactam concentrations were low and even undetectable between each injection in the intermittent administration arm. This was not found within the continuous administration arm. In conclusion, for the intermittent administration, we observed some long periods occurring before each injection while antibiotic concentrations were under the MIC of most bacteria. During these same periods tazobactam concentrations were under the efficacy threshold. These periods were not observed within the continuous administration arm.

Topics: Adolescent; Adult; Aged; Area Under Curve; Bacteria, Anaerobic; Bacterial Infections; Drug Administration Schedule; Drug Therapy, Combination; Enterobacteriaceae Infections; Female; Gram-Positive Bacterial Infections; Humans; Infusions, Intravenous; Male; Microbial Sensitivity Tests; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination

Extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae pose a huge threat to human health, especially in the context of complicated urinary tract infections (cUTIs). Carbapenems and piperacillin-tazobactam (PTZ) are two antimicrobial agents commonly used to treat cUTIs.. A monocentric retrospective cohort study focused on the treatment of cUTIs in adults was conducted from January 2019 to November 2021. Patients with a positive urine culture strain yielding ≥ 103 colony-forming units per milliliter (CFU/mL), and sensitive to PTZ and carbapenems, were included. The primary endpoint was clinical success after antibiotic therapy. The secondary endpoint included rehospitalization and 90-day recurrence of cUTIs caused by ESBL-producing Enterobacteriaceae.. Of the 195 patients included in this study, 110 were treated with PTZ while 85 were administered meropenem. The rate of clinical cure was similar between the PTZ and meropenem groups (80% vs. 78.8%, p = 0.84). However, the PTZ group had a lower duration of total antibiotic use (6 vs. 9; p < 0.01), lower duration of effective antibiotic therapy (6 vs. 8; p < 0.01), and lower duration of hospitalization (16 vs. 22; p < 0.01).. In terms of adverse events, the safety of PTZ was higher than that of meropenem in the treatment of cUTIs.

Topics: Adult; Anti-Bacterial Agents; beta-Lactamase Inhibitors; beta-Lactamases; Carbapenems; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Meropenem; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pyelonephritis; Retrospective Studies; Urinary Tract Infections

Extended-spectrum β-lactamase (ESBL)-producing Enterobacterales are a global threat to public health due to their antimicrobial resistance profile and, consequently, their limited available treatment options. Tazobactam is a sulfone β-lactamase inhibitor with in vitro inhibitory activity against common ESBLs in Enterobacterales, including CTX-M. However, the role of tazobactam-based combinations in treating infections caused by ESBL-producing Enterobacterales remains unclear. In the United States, two tazobactam-based combinations are available, piperacillin-tazobactam and ceftolozane-tazobactam. We evaluated and compared the roles of tazobactam-based combinations against ESBL-producing organisms with emphasis on pharmacokinetic/pharmacodynamic exposures in relation to MIC distributions and established breakpoints, clinical outcomes data specific to infection site, and considerations for downstream effects with these agents regarding antimicrobial resistance development. While limited data with ceftolozane-tazobactam are encouraging for its potential role in infections due to ESBL-producing Enterobacterales, further evidence is needed to determine its place in therapy. Conversely, currently available microbiologic, pharmacokinetic, pharmacodynamic, and clinical data do not suggest a role for piperacillin-tazobactam, and we caution clinicians against its usage for these infections.

Topics: Anti-Bacterial Agents; beta-Lactamases; Cephalosporins; Drug Combinations; Enterobacteriaceae Infections; Humans; Pharmacists; Piperacillin, Tazobactam Drug Combination; Societies, Medical; Tazobactam; United States

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

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamase Inhibitors; beta-Lactamases; Carbapenems; Cephalosporin Resistance; Cohort Studies; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Meta-Analysis as Topic; Multicenter Studies as Topic; Observational Studies as Topic; Piperacillin, Tazobactam Drug Combination; Randomized Controlled Trials as Topic

We studied the performance of aminoglycosides in treating bloodstream infections (BSIs) of urinary source caused by ESBL-producing Enterobacteriaceae (ESBL-EB).. In a retrospective study of 193 patients with a clinical diagnosis of urinary tract infection, pyelonephritis or urosepsis and blood and urine cultures positive for ESBL-EB, patients were grouped according to whether they were treated with an aminoglycoside, a carbapenem or piperacillin/tazobactam. Multivariate analysis was used to define risk factors for mortality with inverse probability of treatment weighting used to minimize confounding. The primary efficacy outcome was 30 day mortality. The primary safety outcome was acute kidney injury (AKI) at 14 days.. Mean age was 79.3 years. Dementia, chronic kidney disease and the presence of a urinary catheter were common. Thirty-two (16.6%) patients died and risk factors for mortality included age, high Charlson score, presentation with severe sepsis/septic shock and infection with bacteria other than Escherichia coli. Aminoglycosides were non-inferior compared with other antibiotics regarding 30 day mortality [13.0% versus 21.2%, respectively; adjusted risk difference=10.29% (-0.82% to 21.41%)], but did not reach non-inferiority for bacteriuria recurrence [48.9% versus 44.7%, respectively; adjusted risk difference=-8.72% (-30.87% to 13.43%)]. AKI developed at a similar rate in both treatment groups: 12.0% versus 10.6%, respectively [OR=1.14 (0.46-2.81)]. Aminoglycosides were more efficacious in E. coli infections compared with other ESBL-EB.. We demonstrated the efficacy and safety of aminoglycosides in treating BSI of urinary source caused by ESBL-EB. This carbapenem-sparing approach can assist in avoiding excessive carbapenem use without compromising outcomes.

Topics: Aged; Aminoglycosides; Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Carbapenems; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli; Humans; Piperacillin, Tazobactam Drug Combination; Pyelonephritis; Retrospective Studies; Urinary Tract Infections

AmpC β-lactamases are found in Enterobacter species, Serratia species, Citrobacter freundii, Providencia species and Morganella morganii ('ESCPM'). Carbapenems are commonly used to treat severe 'ESCPM' infections. Carbapenem-sparing agents are needed because of increasing carbapenem resistance worldwide. Use of cefepime and piperacillin-tazobactam has limited supportive clinical data. We evaluated the efficacy of non-carbapenems vs. carbapenems in 'ESCPM' bacteraemia.. A retrospective cohort study was conducted on patients with 'ESCPM' bacteraemia. Primary outcome was 30-day mortality. Analyses were performed on patients who received carbapenems vs. piperacillin-tazobactam or cefepime monotherapy as empirical and definitive therapy. Propensity score for carbapenem therapy was adjusted for in multivariate analyses for 30-day mortality.. A total of 241 patients were included. The most common bacterium isolated was Enterobacter species (58.1%). Common sources were urinary (22.8%) and vascular lines (22.0%). Carbapenems (28.6%) and piperacillin-tazobactam (28.6%) were the commonest empirical antibiotics. Carbapenems (54.8%) and cefepime (23.7%) were the most common definitive antibiotics. Median Pitt bacteraemia score was 1 (interquartile range [IQR], 0-2). Overall, 30-day mortality was 12.9%. Adjusted multivariate analyses for empirical and definitive antibiotic treatment models yielded risk factors for 30-day mortality, including higher Pitt bacteraemia score (empirical: adjusted OR [aOR] 1.21 for each point increase, 95% confidence interval [CI]:1.01-1.45; definitive: aOR 1.33 for each point increase, 95% CI:1.06-1.69) and age (empirical: aOR 1.04 for each year increase, 95% CI:1.01-1.08). Empirical piperacillin-tazobactam (aOR 0.29, 95% CI:0.07-1.27) and definitive cefepime (aOR 0.65, 95% CI:0.12-3.55) were not associated with 30-day mortality.. Compared with carbapenem therapy, empirical piperacillin-tazobactam and definitive cefepime were not associated with 30-day mortality in 'ESCPM' bacteraemia.

Topics: Aged; Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; beta-Lactamase Inhibitors; beta-Lactamases; Carbapenems; Cefepime; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Humans; Male; Middle Aged; Piperacillin, Tazobactam Drug Combination; Retrospective Studies

To determine the percentage of patients given standard doses of piperacillin/tazobactam or meropenem by continuous  infusion who achieved the target pharmacokinetic/pharmacodynamic  (PK/PD) index, which was defined as free concentrations four times  more than the minimum inhibitory concentration (CMI) for 100% of the  dosing interval (100% fT≥ 4 x MIC).. Preliminary data from a larger prospective clinical study  analysing the PK/PD behaviour of β-lactams antibiotics continuous  infusion (CI) in critical patients. The study was conducted in the  intensive care units of a tertiary university hospital for adults (June  2015-May 2017). Inclusion criteria: normal renal function (glomerular  renal function (GFR) CKD-EPI formula ≥ 60 mL/min/1.73 m2) and  treatment with standard dose β-lactams CI. Concentrations at steady  state (Css) conditions were determined using UHPLC-MS/MS. We  selected the highest susceptible MIC for all likely organisms according to  European Commitee on Antimicrobial Susceptibility Testing's (i.e.  piperacillin/tazobactam: 8 mg/L for enterobacteriaceae and 16 mg/L for  Pseudomonas aeruginosa; meropenem: 2 mg/L for any  microorganism). In addition, a subanalysis of patients was conducted using actual MIC values.. 61 patients were enrolled (25 to meropenem and 36 to  piperacillin/tazobactam). Average age was 59 (15) years and median  GFR rate was 95 mL/min/1.73 m2 (83-115). Median meropenem and  piperacillin free concentrations were 16 mg/L (11-29) and 40 mg/L (21- 51), respectively. 88% of patients treated with meropenem reached the  PK/PD target, without differences between both microorganisms. For  piperacillin/tazobactam, 61% and 11% of patients reached the target,  with enterobacteriaceae and Pseudomonas as suspected  microorganisms, respectively. The pathogen was isolated in 35 (57%)  patients: 94% reached the target PK/PD, without differences between  both antibiotic therapies.. Standard doses of meropenem CI are sufficient to  achieve a PK/PD target of 100% fT≥ 4 x MIC in suspected infections  with high MICs (Pseudomonas aeruginosa or enterobacteriaceae).  However, higher doses of piperacillin/tazobactam could be considered to  achieve this goal. In patients with isolated microorganisms, a  standard dose of both antibiotic therapies would be sufficient to achieve  the target. Therapeutic drug monitoring is highly recommended for  therapeutic optimization.. Objetivo: Determinar el porcentaje de pacientes, a los que se les  administró dosis estándar de piperacilina/tazobactam o meropenem en  perfusión continua, que alcanzaban el índice  farmacocinético/farmacodinámico diana definido como el 100% del  intervalo de administración en que las concentraciones de antibiótico  libre fueron cuatro veces iguales o superiores a la concentración mínima  inhibitoria (100% fT ≥ 4 x CMI).Método: Datos preliminares obtenidos de un estudio clínico prospectivo que analiza el comportamiento  farmacocinético/farmacodinámico de los antibióticos betalactámicos  administrados en perfusión continua en pacientes críticos. Se realizó en  unidades de cuidados intensivos de un hospital universitario de tercer  nivel, desde junio de 2015 a mayo de 2017. Criterios de inclusión:  adultos con función renal correcta (filtrado glomerular según la fórmula  CKD-EPI ≥ 60 ml/min/1,73 m2) y tratados con dosis estándar de  antibióticos betalactámicos en perfusión continua. Las concentraciones  en estado de equilibrio estacionario fueron determinadas mediante  cromatografía líquida acoplada a espectrometría de masas (UHPLC- MS/MS). Se utilizaron valores de concentración mínima  inhibitoria  teóricos para microorganismos más resistentes (piperacilina/ tazobactam: 16 mg/l para Pseudomonas aeruginosa y 8 mg/l para Enterobacteriaceae; meropenem: 2 mg/l, independientemente del  microorganismo). Además, se realizó un subanálisis de los pacientes con aislamiento microbiológico (concentraciones mínimas inhibitorias  reales).Resultados: Se incluyeron 61 pacientes (25 meropenem y 36  piperacilina/ tazobactam). Edad media 59 años (15), mediana de  filtrado glomerular 95 ml/min/1,73 m2 (83-115). Mediana de  concentraciones en estado de equilibrio estacionario libre: 16 mg/l (11- 29) meropenem y 40 mg/l (21-51) piperacilina. El 88% de los pacientes  tratados con meropenem alcanzaron el objetivo  farmacocinético/farmacodinámico, sin diferencias entre Enterobacteriaceae y Pseudomonas. En el caso de  piperacilina/tazobactam, el 61% y el 11% de los pacientes alcanzaron la  diana, considerando Enterobacteriaceae y Pseudomonas como  microorganismo sospechoso. Un total de 35 (57%) pacientes  presentaron aislamiento microbiológico. El 94% de ellos alcanzaron la  diana, sin diferencias entre los dos antibióticos.Conclusiones: Ante la sospecha de infecciones por microorganismos con concentraciones mínimas inhibitorias elevadas  (Pseudomonas aeruginosa o enterobacterias),

Topics: Adult; Aged; Anti-Bacterial Agents; Clinical Studies as Topic; Critical Illness; Cross Infection; Enterobacteriaceae Infections; Female; Hospitals, University; Humans; Infusions, Intravenous; Intensive Care Units; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Pseudomonas Infections; Tertiary Care Centers

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: Aged; Anti-Bacterial Agents; Craniotomy; Drug Resistance, Multiple, Bacterial; Empyema; Enterobacteriaceae Infections; Humans; Male; Meningeal Neoplasms; Meropenem; Piperacillin, Tazobactam Drug Combination; Postoperative Complications; Seizures; Spinal Puncture; Staphylococcal Infections; Surgical Wound Infection; Treatment Outcome; Vancomycin

Topics: Anti-Bacterial Agents; beta-Lactamase Inhibitors; beta-Lactamases; Enterobacteriaceae Infections; Escherichia coli; Humans; Klebsiella pneumoniae; Multicenter Studies as Topic; Piperacillin, Tazobactam Drug Combination; Randomized Controlled Trials as Topic; Sepsis; Survival Analysis; Treatment Outcome

A man in his late 50s presented to the emergency room with a 1-month history of severe abdominal pain and an endoscopic fishbone retrieval from his rectum. Serial CT scans revealed a fishbone located in the patient's upper abdomen, which had migrated through the stomach wall, into the periportal space, causing a contained gastric perforation, development of a porta hepatis abscess and secondary portal vein thrombosis. Furthermore, the sharp tip of the fishbone lay 5 mm from the patient's hepatic artery. He was transferred to a hepatobiliary centre where he underwent urgent exploratory laparotomy, with surgical exploration of the porta, drainage of the abscess and retrieval of the fishbone. Postoperatively, he received further treatment with antibiotics and anticoagulation and recovered without further sequelae.

Topics: Abdominal Abscess; Abdominal Pain; Aged; Anticoagulants; Diagnosis, Differential; Enterobacteriaceae Infections; Foreign-Body Migration; Heparin; Humans; Male; Piperacillin, Tazobactam Drug Combination; Portal Vein; Streptococcal Infections; Thrombosis; Tomography, X-Ray Computed

This study aimed to assess the prognostic factors of patients with bacteremia due to extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) as well as the antimicrobial susceptibility, particularly to piperacillin/tazobactam (PTZ), among ESBL-PE strains. The medical records of 65 patients with ESBL-PE bacteremia divided into the survivor group (n = 52) and nonsurvivor group (n = 13) were retrospectively reviewed. The male-to-female ratio, age, underlying disease, leukocyte count, C-reactive protein level, and treatment did not differ between the 2 groups. Multivariate analysis showed that the independent predictors associated with hospital mortality of ESBL-PE bacteremia were sepsis (P = 0.047) and febrile neutropenia (P = 0.008); thus, early assessment of these conditions is important. Further, the minimum inhibitory concentration values of ESBL-PE isolates in nonsurvivors tended to be higher than those in survivors. PTZ should be used with caution in cases of ESBL-PE strains with low susceptibility to the drug.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; beta-Lactamase Inhibitors; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Risk Factors; Survival Analysis

Enterobacter spp. are a common cause of nosocomial pneumonia and treatment can be complicated by AmpC resistance. Carbapenems are the treatment of choice; however, alternatives are needed. Cefepime has been shown to be non-inferior to carbapenems. There are limited data to support the use of piperacillin/tazobactam. The objective of this study was to determine if piperacillin/tazobactam is non-inferior to cefepime or ertapenem for Enterobacter pneumonia treatment.. To compare the rate of clinical cure in patients with Enterobacter pneumonia receiving definitive treatment with piperacillin/tazobactam, cefepime, or ertapenem. Secondary outcomes included hospital mortality, infection-related length of stay, duration of mechanical ventilation, recurrent pneumonia, and resistance.. Retrospective, single-center study.. Of 114 patients included, 59 received definitive treatment with piperacillin/tazobactam and 55 received cefepime or ertapenem. There was no difference in the proportion of patients who achieved clinical cure in the piperacillin/tazobactam group compared to the cefepime or ertapenem group (76.3% vs. 87.3%, P = 0.13). Treatment group was not associated with clinical cure when controlling for confounders in multivariable logistic regression (adjusted odds ratio [OR] 0.59, 95% confidence interval [CI] 0.15-2.37). The rate of recurrent pneumonia was 11.4% in the piperacillin/tazobactam group and 6.7% in the cefepime or ertapenem group (P = 0.48). Other secondary outcomes did not differ between the groups.. In this retrospective study of patients with Enterobacter pneumonia, clinical cure with piperacillin/tazobactam was comparable to that with cefepime or ertapenem; however, a prospective trial with a larger population is needed to determine if definitive treatment with piperacillin/tazobactam is non-inferior to definitive treatment with cefepime or ertapenem.

Topics: Aged; Anti-Bacterial Agents; Cefepime; Enterobacter; Enterobacteriaceae Infections; Ertapenem; Female; Humans; Male; Middle Aged; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial; Retrospective Studies; Treatment Outcome

We present an elderly diabetic man with left hallux pain and drainage who was initially diagnosed with acute gouty arthritis using the diagnostic rule for acute gout and monosodium urate crystals presented on synovial fluid analysis. Further investigation with surgical debridement, plain X-ray, MRI and wound culture revealed concomitant

Topics: Aged, 80 and over; Anti-Bacterial Agents; Arthritis, Gouty; Citrobacter koseri; Debridement; Diabetic Foot; Enterobacteriaceae Infections; Ertapenem; Humans; Male; Osteomyelitis; Piperacillin, Tazobactam Drug Combination; Treatment Outcome; Vancomycin

There are several empiric antibiotic treatment options for febrile neutropenia, yet there is no universally-accepted initial protocol. We aimed to assess the performance of a protocol (piperacillin, gentamicin and cefazolin) introduced over 40 years ago and compare its coverage against bacteria isolated from blood of neutropenic patients with that of various commonly used antibiotic treatment protocols.. Adults with neutropenia admitted between 2003 and 2012 to the hemato-oncologic departments and in whom blood cultures were taken on admission were included. Appropriateness of several common antibiotic protocols was assessed based on the susceptibility of the blood isolates. Crude mortality rates were computed by the susceptibility of bacteria isolated from patients' blood to the actual treatment given.. In total, 180 admissions of neutropenic patients (95 in patients who had fever above 38 °C) with positive blood cultures were analyzed. The actual antibiotic regimen prescribed was deemed appropriate in 82% of bacteremia episodes. The recommended institutional protocol was used in 62% of bacteremia episodes in neutropenic patients. This protocol would have been appropriate in 85% of all neutropenic bacteremia episodes and 89% of episodes in febrile neutropenia patients compared with piperacillin/tazobactam (79%, P = 0.13 and 76%, P = 0.002, respectively) and imipenem (93%, P = 0.004 and 92%, P = 0.74, respectively). Isolation of bacteria resistant to the actual antibiotic treatment given was associated with higher mortality at one week and at 30 days.. Common current antibiotic regimens provide similar coverage among febrile neutropenic patients, whereas broad spectrum antibiotic combinations maximize coverage among neutropenic patients.

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Blood Culture; Carbapenem-Resistant Enterobacteriaceae; Cefazolin; Clinical Protocols; Enterobacteriaceae Infections; Gentamicins; Humans; Imipenem; Microbial Sensitivity Tests; Middle Aged; Neoplasms; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Staphylococcal Infections; Staphylococcus aureus; Streptococcal Infections; Streptococcus

This study evaluated the in vitro activity of ceftolozane-tazobactam and comparator agents tested against Enterobacteriaceae and Pseudomonas aeruginosa isolates from hospitalized patients in the United States. Ceftolozane-tazobactam is an antipseudomonal cephalosporin combined with a well-established β-lactamase inhibitor. A total of 18,960 organisms (15,223 Enterobacteriaceae and 3,737 P. aeruginosa) were consecutively collected from 32 medical centers located in all nine U.S. census divisions from 2013 to 2016. Organisms were tested for susceptibility by broth microdilution. CLSI and EUCAST interpretive criteria were used. Ceftolozane-tazobactam (94.4% susceptible), amikacin (99.0% susceptible), and meropenem (98.0% susceptible) were the most active compounds tested against Enterobacteriaceae. Among the Enterobacteriaceae isolates tested, 1.9% (n = 286) were carbapenem-resistant Enterobacteriaceae (CRE) and 9.5% (n = 1,450) exhibited an extended-spectrum β-lactamase (ESBL) non-CRE phenotype. Although ceftolozane-tazobactam showed good activity against ESBL non-CRE phenotype strains of Enterobacteriaceae (87.5% susceptible), it lacked useful activity against CRE. Ceftolozane-tazobactam was the most potent β-lactam agent tested against P. aeruginosa isolates, with 97.3% susceptible. Only colistin was more active, inhibiting 99.5% of isolates. Ceftolozane-tazobactam also maintained good activity against multidrug-resistant P. aeruginosa, with 88.6% susceptible. Ceftolozane-tazobactam was the most active β-lactam agent tested against P. aeruginosa and was more active than available cephalosporins and piperacillin-tazobactam against Enterobacteriaceae.

Topics: Amikacin; Anti-Bacterial Agents; Cephalosporins; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Hospitals; Humans; Meropenem; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pseudomonas aeruginosa; Pseudomonas Infections; Tazobactam; Thienamycins

The activities of ceftolozane-tazobactam and comparator agents against organisms deemed to be the cause of pneumonia among patients hospitalized in the United States during 2013 to 2015 were evaluated. Organisms included 1,576

Topics: Anti-Bacterial Agents; beta-Lactamases; Cefepime; Ceftazidime; Cephalosporins; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Gene Expression; Hospitalization; Humans; Isoenzymes; Meropenem; Microbial Sensitivity Tests; Piperacillin, Tazobactam Drug Combination; Plasmids; Pneumonia, Bacterial; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory System; Retrospective Studies; Tazobactam; United States

The ongoing extended spectrum β-lactamase-producing. This ward-level multicentre retrospective study was based on data from French antibiotic and multidrug-resistant bacteria surveillance networks in healthcare facilities. Antibiotic use was expressed in defined daily doses per 1000 patient-days. Factors associated with the reduction in carbapenem use (yes/no) over the study period were determined from random-effects logistic regression model (493 wards nested within 259 healthcare facilities): ward characteristics (type, size…), ward antibiotic use (initial antibiotic use [i.e., consumption of a given antibiotic in 2009], initial antibiotic prescribing profile [i.e., proportion of a given antibiotic in the overall antibiotic consumption in 2009] and reduction in the use of a given antibiotic between 2009 and 2013) and regional ESBL-PE incidence rate in acute care settings in 2011.. Our study suggests that a decrease in 3GCs in the overall antibiotic use and the continuation of reduction in fluoroquinolone use, could allow reducing carbapenem use, given the well-demonstrated role of 3GCs and fluoroquinolones in the occurrence of ESBL-PE. Thus, antibiotic stewardship programs should target wards with higher 3GC prescription proportions to reduce them.

Topics: Anti-Bacterial Agents; Antimicrobial Stewardship; beta-Lactam Resistance; beta-Lactamases; Carbapenems; Cephalosporins; Cross Infection; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Fluoroquinolones; France; Glycopeptides; Guidelines as Topic; Hospitals; Humans; Intensive Care Units; Logistic Models; Piperacillin, Tazobactam Drug Combination; Practice Patterns, Physicians'; Prescriptions; Probability; Retrospective Studies

Febrile neutropenia (FN) is associated with substantial morbidity and necessitates empirical broad-spectrum antimicrobial treatment. In this prospective cohort study, a risk-guided management strategy for FN using empirical piperacillin/tazobactam (TZP) or a carbapenem was evaluated. The analysis involved 723 FN episodes in hospitalised adult patients, including those with severe sepsis or prior infection/colonisation with extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae. Propensity score matching analysis was used to adjust for baseline differences between treatment groups and produced 267 matched pairs. The primary outcome was all-cause mortality. Secondary outcomes were the incidences of drug-resistant Gram-negative (including ESBL-producing) and Gram-positive bacterial isolates and of invasive pulmonary aspergillosis (IPA) and their associated mortality. There was no difference in mortality between empirical carbapenem and TZP [18/267 (6.7%) vs. 14/267 (5.2%); P = 0.466]. Higher incidences of drug-resistant Gram-negative isolates [77/267 (28.8%) vs. 26/267 (9.7%); P < 0.001], including ESBL-producing bacteria [57/267 (21.3%) vs. 16/267 (6.0%); P < 0.001], were observed in carbapenem-treated episodes where its use lowered mortality. Mortality rates for ESBL-positive infections were 5.3% (3/57) and 25.0% (4/16) (P = 0.037) and for drug-resistant Gram-negative infections were 6.5% (5/77) and 23.1% (6/26) (P = 0.018) in carbapenem- and TZP-treated episodes, respectively. More IPA was observed with carbapenem use [16/267 (6.0%) vs. 6/267 (2.2%); P = 0.029]. Antifungal prophylaxis reduced the risk of death (odds ratio = 0.39, 95% confidence interval 0.17-0.87; P = 0.017). Risk-guided carbapenem prescribing in FN correctly identified cases prone to drug-resistant Gram-negative infections and reduced the mortality in these episodes.

Topics: Anti-Bacterial Agents; Antifungal Agents; Bacteremia; beta-Lactam Resistance; beta-Lactamases; Carbapenems; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Febrile Neutropenia; Humans; Invasive Pulmonary Aspergillosis; Piperacillin, Tazobactam Drug Combination; Prospective Studies

A total of 18,656 Enterobacteriaceae and 4,175 Pseudomonas aeruginosa were consecutively collected from 85 US hospitals and tested for susceptibility by broth microdilution methods in a central monitoring laboratory (JMI Laboratories). The antimicrobial susceptibility and frequency of key resistance phenotypes were assessed and stratified by infection type as follows: bloodstream (BSI; 3,434 isolates; 15.0%), pneumonia (6,439; 28.2%), skin and skin structure (SSSI; 4,134; 18.1%), intra-abdominal (IAI; 951; 4.2%), and urinary tract (UTI; 7,873; 34.5%). Ceftazidime-avibactam was active against 99.9% to 100.0% of Enterobacteriaceae and 97.0% (pneumonia) to 99.4% (UTI) of P. aeruginosa isolates. Susceptibility rates were consistently lower for β-lactams, such as ceftazidime (82.3% vs. 87.1-90.8%), piperacillin-tazobactam (87.5% vs. 90.2-95.6%), and meropenem (96.8% vs. 98.4-99.4%) among Enterobacteriaceae from pneumonia compared to other infection types. Susceptibility to gentamicin was also generally lower among isolates from pneumonia, whereas susceptibility to levofloxacin and colistin were lowest among BSI and SSSI isolates, respectively. The occurrence of multidrug-resistance (MDR; 8.2% overall), extensively drug-resistance (XDR; 1.1% overall), and carbapenem-resistant Enterobacteriaceae (CRE; 1.3% overall) phenotypes were markedly higher among isolates from patients with pneumonia compared to other infection types. Among P. aeruginosa, susceptibility rates for ceftazidime, piperacillin-tazobactam, and gentamicin were lowest among isolates from pneumonia, whereas susceptibility to meropenem was similar among isolates from BSI, pneumonia, and IAI (77.3-77.9%), and susceptibility to levofloxacin was markedly lower among UTI isolates (67.1%). The frequencies of P. aeruginosa isolates with MDR and XDR phenotypes were highest among isolates from patients with pneumonia.

Topics: Anti-Bacterial Agents; Azabicyclo Compounds; Ceftazidime; Colistin; Cross Infection; Drug Combinations; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Meropenem; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pseudomonas aeruginosa; Pseudomonas Infections; Thienamycins; United States

Management of micro-organisms harbouring AmpC β-lactamases remains challenging. Carbapenems are often considered first-line agents. Due to growing concern regarding carbapenem-resistant Enterobacteriaceae, integrating non-carbapenem treatment strategies is being explored for these pathogens. The primary objective of this study was to evaluate clinical outcomes in patients with bacteraemia secondary to AmpC-producing organisms treated with cefepime or piperacillin/tazobactam (TZP). A retrospective study of adult patients receiving cefepime or TZP for the treatment of AmpC -producing organisms with positive cefoxitin screen (i.e. Citrobacter, Enterobacter or Serratia spp. along with cefoxitin resistance) isolated from blood cultures was conducted. The primary endpoint was clinical cure at end of therapy (EOT). Secondary endpoints included microbiological eradication, frequency of susceptibility changes following treatment, and 7- and 30-day all-cause mortality. Clinical cure at EOT was 87.1%, with 93.2% of patients achieving microbiological eradication. The 7- and 30-day mortality rates were 3.8% and 10.6%, respectively. Organism susceptibility was exceptionally high, with minimum inhibitory concentrations (MICs) of ≤2 μg/mL in 90% of patients treated with cefepime (n = 108). Selection for resistance to third-generation cephalosporins or primary antimicrobial therapy was infrequent at 6.1% (8/132). In conclusion, use of cefepime or TZP for management of AmpC bloodstream infections was associated with clinical and microbiological cure with infrequent selection for resistance.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Antimicrobial Stewardship; Bacteremia; Bacterial Proteins; beta-Lactamase Inhibitors; beta-Lactamases; Cefepime; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Survival Analysis; Treatment Outcome; Young Adult

To study the evolution in the susceptibility of Enterobacter spp. in Crete, Greece from 2010 to 2015.. Non-duplicate isolates were studied using automated systems. Phenotypic confirmatory tests were applied.. A total of 939 Enterobacter isolates were included. Colistin was the most active antibiotic (97.9%) followed by imipenem (96.1%), gentamicin (95.7%), tigecycline (91.8%), cefepime (89.4%), chloramphenicol (85.8%), fosfomycin (85.5%), trimethoprim/sulfamethoxazole (83.3%) and piperacillin/tazobactam (73.3%). Antibiotic resistance did not increase during the study period for most antibiotics. Lower susceptibility was observed among multidrug-resistant strains and carbapenem-nonsusceptible isolates. AmpC was the most common resistant mechanism (21%); carbapenemases (3.7%) and aminoglycoside-modifying enzymes (6.5%) were also detected.. A significant proportion of Enterobacter spp. was resistant to several antibiotics, most notably β-lactams.

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; beta-Lactams; Carbapenems; Cefepime; Cephalosporins; Child; Colistin; Drug Resistance, Multiple, Bacterial; Enterobacter; Enterobacteriaceae Infections; Greece; Hospitals, University; Humans; Microbial Sensitivity Tests; Minocycline; Penicillanic Acid; Phenotype; Piperacillin; Piperacillin, Tazobactam Drug Combination; Tigecycline

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

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamase Inhibitors; beta-Lactamases; beta-Lactams; Carbapenem-Resistant Enterobacteriaceae; Cefotaxime; Ceftazidime; Disk Diffusion Antimicrobial Tests; Enterobacteriaceae Infections; Ertapenem; Fluoroquinolones; Humans; Nigeria; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactams; Connecticut; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli; Female; Humans; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Penicillanic Acid; Phenotype; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prevalence; Retrospective Studies; Risk Factors; Treatment Outcome

To evaluate the antimicrobial susceptibility of Gram-negative bacilli that caused hospital-acquired and community-acquired intra-abdominal infections (IAIs) in China between 2012 and 2013, we determined the susceptibilities to 12 antimicrobials and the extended-spectrum β-lactamase (ESBL) statuses of 3,540 IAI isolates from seven geographic areas in China in a central laboratory using CLSI broth microdilution and interpretive standards. Most infections were caused by Escherichia coli (46.3%) and Klebsiella pneumoniae (19.7%). Rates of ESBL-producing E. coli (P = 0.031), K. pneumoniae (P = 0.017), and Proteus mirabilis (P = 0.004) were higher in hospital-acquired IAIs than in community-acquired IAIs. Susceptibilities of enterobacteriaceae to ertapenem, amikacin, piperacillin-tazobactam, and imipenem were 71.3% to 100%, 81.3% to 100%, 64.7% to 100%, and 83.1% to 100%, respectively, but imipenem was ineffective against P. mirabilis (<20%). Although most ESBL-positive hospital-acquired isolates were resistant to third- and fourth-generation cephalosporins, the majority were susceptible to cefoxitin (47.9% to 83.9%). Susceptibilities of ESBL-positive isolates to ampicillin-sulbactam (<10%) were low, whereas susceptibilities to ciprofloxacin (0% to 54.6%) and levofloxacin (0% to 63.6%) varied substantially. The prevalences of cephalosporin-susceptible E. coli and K. pneumoniae were higher in the northeastern and southern regions than in the central and eastern regions, reflecting the ESBL-positive rates in these areas, and were lowest in the Jiangsu-Zhejiang (Jiang-Zhe) area where the rates of carbapenem resistance were also highest. Ertapenem, amikacin, piperacillin-tazobactam, and imipenem are the most efficacious antibiotics for treating IAIs in China, especially those caused by E. coli or K. pneumoniae. Resistance to cephalosporins and carbapenems is more common in the Jiang-Zhe area than in other regions in China.

Topics: Amikacin; Ampicillin; Anti-Bacterial Agents; beta-Lactamases; beta-Lactams; Cefoxitin; China; Ciprofloxacin; Community-Acquired Infections; Cross Infection; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Ertapenem; Gene Expression; Humans; Imipenem; Intraabdominal Infections; Levofloxacin; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sulbactam

Our objective was to evaluate the impact of low versus borderline MIC of piperacillin/tazobactam on the clinical outcomes of patients with bacteraemia caused by Enterobacteriaceae who were treated with that antimicrobial.. A prospective observational multicentre cohort study was conducted in 13 Spanish university hospitals. Patients >17 years old with bacteraemia due to Enterobacteriaceae who received empirical piperacillin/tazobactam treatment for at least 48 h were included. Outcome variables were clinical response at day 21, clinical response at end of treatment with piperacillin/tazobactam and all-cause 30 day mortality. Univariate and multivariate logistic regression analyses were performed.. Overall, 275 patients were included in the analysis; 248 (90.2%) in the low MIC group (≤ 4 mg/L) and 27 (9.8%) in the borderline MIC group (8-16 mg/L). The biliary tract was the most common source of infection (48.4%) and Escherichia coli was the most frequent pathogen (63.3%). Crude 30 day mortality rates were 10.5% and 11.1% for the low MIC group and the borderline MIC group, respectively (relative risk = 1.06, 95% CI = 0.34-3.27, P = 1). Multivariate analysis of failure at day 21 and at end of treatment with piperacillin/tazobactam and 30 day mortality showed no trend towards increased clinical failure or mortality with borderline MICs (OR = 0.96, 95% CI = 0.18-4.88, P = 0.96; OR = 0.47, 95% CI = 0.10-2.26, P = 0.35; OR = 1.48, 95% CI = 0.33-6.68, P = 0.6).. We did not find that higher piperacillin/tazobactam MIC within the susceptible or intermediate susceptibility range had a significant influence on the outcome for patients with bacteraemia due to Enterobacteriaceae.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacteremia; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Hospitals, University; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Spain; Survival Analysis; Treatment Outcome; Young Adult

The study objective was to evaluate the population pharmacokinetics and pharmacodynamics of extended-infusion piperacillin-tazobactam in children hospitalized in an intensive care unit. Seventy-two serum samples were collected at steady state from 12 patients who received piperacillin-tazobactam at 100/12.5 mg/kg of body weight every 8 h infused over 4 h. Population pharmacokinetic analyses were performed using NONMEM, and Monte Carlo simulations were performed to estimate the piperacillin pharmacokinetic profiles for dosing regimens of 80 to 100 mg/kg of the piperacillin component given every 6 to 8 h and infused over 0.5, 3, or 4 h. The probability of target attainment (PTA) for a cumulative percentage of the dosing interval that the drug concentration exceeds the MIC under steady-state pharmacokinetic conditions (TMIC) of ≥50% was calculated at MICs ranging from 0.25 to 64 mg/liter. The mean ± standard deviation (SD) age, weight, and estimated glomerular filtration rate were 5 ± 3 years, 17 ± 6.2 kg, and 118 ± 41 ml/min/1.73 m(2), respectively. A one-compartment model with zero-order input and first-order elimination best fit the pharmacokinetic data for both drugs. Weight was significantly associated with piperacillin clearance, and weight and sex were significantly associated with tazobactam clearance. Pharmacokinetic parameters (mean ± SD) for piperacillin and tazobactam were as follows: clearance, 0.22 ± 0.07 and 0.19 ± 0.07 liter/h/kg, respectively; volume of distribution, 0.43 ± 0.16 and 0.37 ± 0.14 liter/kg, respectively. All extended-infusion regimens achieved PTAs of >90% at MICs of ≤16 mg/liter. Only the 3-h infusion regimens given every 6 h achieved PTAs of >90% at an MIC of 32 mg/liter. For susceptible bacterial pathogens, piperacillin-tazobactam doses of ≥80/10 mg/kg given every 8 h and infused over 4 h achieve adequate pharmacodynamic exposures in critically ill children.

Topics: Age Factors; Anti-Bacterial Agents; Area Under Curve; Child; Child, Preschool; Computer Simulation; Critical Illness; Drug Administration Schedule; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Glomerular Filtration Rate; Half-Life; Humans; Infant; Intensive Care Units; Male; Microbial Sensitivity Tests; Monte Carlo Method; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sex Factors

Although Morganella morganii causes a variety of clinical infections, there are limited studies on M. morganii bacteremia after the year 2000. A total of 109 patients with M. morganii bacteremia at a medical center in Taiwan from 2003 to 2012 were studied. Among them, 30.3 % had polymicrobial bacteremia and 75.2 % had community-acquired infection. The most common underlying diseases were hypertension (62.4 %) and diabetes mellitus (38.5 %). The urinary tract (41.3 %) was the major portal of entry, followed by the hepatobiliary tract (27.5 %), skin and soft tissue (21.1 %), and primary bacteremia (10.1 %). Susceptibility testing of M. morganii isolates showed ubiquitous resistance to first-generation cephalosporins and ampicillin-clavulanate; resistance rates to gentamicin, piperacillin-tazobactam, and ciprofloxacin were 30.3 %, 1.8 %, and 10.1 %, respectively. Overall, the 14-day mortality was 14.7 %. Univariate analysis revealed that elevated blood urea nitrogen (BUN) values [p = 0.0137, odds ratio (OR) 5.26], intensive care unit (ICU) admission (p = 0.011, OR 4.4), and higher Acute Physiology and Chronic Health Evaluation II (APACHE II) scores (p < 0.001, OR 1.62) were significantly associated with mortality. The APACHE II score remained the only significant risk factor for mortality in multivariate analysis (p = 0.0012, OR 1.55). In conclusion, M. morganii bacteremia patients were mostly elderly, with one or more comorbidities. Most of the patients had community-acquired infection via the urinary and hepatobiliary tracts. Furthermore, prognosis can be predicted according to disease severity measured by the APACHE II score.

Topics: Age Factors; Aged; Aged, 80 and over; Ampicillin; Anti-Bacterial Agents; Bacteremia; Cephalosporins; Community-Acquired Infections; Cross Infection; Drug Resistance, Bacterial; Enterobacteriaceae Infections; Female; Gentamicins; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Morganella morganii; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Risk Factors; Taiwan

The effectiveness of piperacillin-tazobactam (PTZ) for the treatment of extended-spectrum β-lactamase (ESBL) bacteremia is controversial. We compared 14-day mortality of PTZ vs carbapenems as empiric therapy in a cohort of patients with ESBL bacteremia who all received definitive therapy with a carbapenem.. Patients hospitalized between January 2007 and April 2014 with monomicrobial ESBL bacteremia were included. A decrease of >3 doubling dilutions in the minimum inhibitory concentration for third-generation cephalosporins tested in combination with 4 µg/mL of clavulanic acid was used to confirm ESBL status. The primary exposure was empiric therapy, defined as antibiotic therapy administered to a patient before ESBL status was known. Patients were excluded if they did not receive a carbapenem after ESBL production was identified. The primary outcome was time to death from the first day of bacteremia. Propensity scores using inverse probability of exposure weighting (IPW) were used to estimate the probability that a patient would receive PTZ vs carbapenems empirically. We calculated overall hazard ratios for mortality censored at 14 days using Cox proportional hazards models on an IPW-adjusted cohort.. A total of 331 unique patients with ESBL bacteremia were identified. One hundred three (48%) patients received PTZ empirically and 110 (52%) received carbapenems empirically. The adjusted risk of death was 1.92 times higher for patients receiving empiric PTZ compared with empiric carbapenem therapy (95% confidence interval, 1.07-3.45).. PTZ appears inferior to carbapenems for the treatment of ESBL bacteremia. For patients at high risk of invasive ESBL infections, early carbapenem therapy should be considered. Our findings should not be extended to β-lactam/β-lactamase inhibitor combinations in development, as limited clinical data are available for these agents.

Topics: Aged; Anti-Bacterial Agents; Bacteremia; beta-Lactamase Inhibitors; beta-Lactamases; Carbapenems; Cohort Studies; Enterobacteriaceae Infections; Escherichia coli; Female; Humans; Klebsiella oxytoca; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Propensity Score; Proportional Hazards Models; Proteus mirabilis; Survival Rate; Time Factors

We determined the prevalence of ESBL Enterobacteriaceae in urinary tract infections among inpatients, identified risk factors of acquisition, and evaluated the effectiveness of alternatives to carbapenems.. The clinical, microbiological, and therapeutic data as well as the outcomes were recorded for all ESBL-E positive urine samples for three months.. Thirty-one (4%) of the 762 Enterobacteriaceae positive cultures were ESBL producers. The predisposing conditions for being infected with those strains were: immunodepression (61%), recent hospitalization (52%), recent antibiotic therapy (52%), and urinary catheterization (61%). 19% of infections were community acquired. The seven cases of acute pyelonephritis and five of prostatitis were treated with piperacillin-tazobactam (5), fluoroquinolones (4), ceftazidime (2), or carbapenems (only 1) after specialized advice. Four (33%) patients relapsed at week 10: three were immunodepressed and three presented with bacteremia.. Alternatives to carbapenems (especially piperacillin-tazobactam) seem to be a good option for non-bacteremic UTI in immunocompetent patients.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactam Resistance; beta-Lactamases; Catheter-Related Infections; Ceftazidime; Community-Acquired Infections; Cross Infection; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Fluoroquinolones; Hospitalization; Hospitals, University; Humans; Immunocompromised Host; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prevalence; Prostatitis; Recurrence; Retrospective Studies; Risk Factors; Urinary Tract Infections; Young Adult

A recent, frequently quoted study has suggested that for bloodstream infections (BSIs) due to extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL) Escherichia coli, treatment with β-lactam/β-lactamase inhibitors (BLBLIs) might be equivalent to treatment with carbapenems. However, the majority of BSIs originate from the urinary tract. A multicenter, multinational efficacy analysis was conducted from 2010 to 2012 to compare outcomes of patients with non-urinary ESBL BSIs who received a carbapenem (69 patients) vs those treated with piperacillin-tazobactam (10 patients). In multivariate analysis, therapy with piperacillin-tazobactam was associated with increased 90-day mortality (adjusted odds ratio, 7.9, P=.03). For ESBL BSIs of a non-urinary origin, carbapenems should be considered a superior treatment to BLBLIs.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Carbapenems; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Hospital Mortality; Humans; Intraabdominal Infections; Length of Stay; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial; Skin Diseases, Bacterial; Soft Tissue Infections

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

Morganella morganii is a gram-negative, facultative anaerobic bacillus whose natural habitat is the gastrointestinal system. While it rarely causes infection alone, it is generally encountered in people with suppressed immunity and in cases of hospital infection. It may also manifest itself as a superinfection. Morganella morganii often demonstrates a course characterized by slow-paced progression with occasional attacks and remissions. Osteoarticular pathologies are not commonly observed in Morganella morganii infections and it has a high mortality rate. We present a 56-year-old male patient with Morganella morganii osteomyelitis in the distal femur and proximal tibia, complicated by septic arthritis in the knee joint.

Topics: Anti-Bacterial Agents; Arthritis, Infectious; Enterobacteriaceae Infections; Fatal Outcome; Femur; Humans; Knee Joint; Magnetic Resonance Imaging; Male; Middle Aged; Morganella morganii; Osteomyelitis; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Tibia

Raoultella planticola (formerly Klebsiella planticola) is a Gram-negative bacterium that has been rarely reported in association with human infection. Here we describe a case of cholangitis complicated with septic shock caused by R. planticola in an immunocompromised patient with advanced cancer who underwent endoscopic retrograde cholangiopancreatography to extract common bile duct stones. The infection was cleared by piperacillin-tazobactam treatment.

Topics: Aged; Anti-Bacterial Agents; Cholangitis; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Immunocompromised Host; Male; Neoplasms; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Shock, Septic; Treatment Outcome

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

To determine the susceptibility pattern of beta-lactam beta-lactamase inhibitor combinations against extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae in urinary isolates.. Observational study.. Ziauddin University Hospital, Karachi, from February to October 2008.. A total of 190 consecutive non-duplicate isolates of ESBL producing Enterobacteriaceae from urine samples of in-patients were included in the study. Urinary samples from out-patients, repeat samples and non-ESBL producing isolates were excluded. Detection of ESBL was carried out by double disk diffusion technique. Antimicrobial susceptibility testing was performed using modified Kirby Bauer's disk diffusion method according to CLSI guidelines. Statistical analysis was performed by SPSS version 10.. Of the 190 ESBL isolates tested, 88 cases (46.31%) were sensitive and 6 cases (3.15%) were resistant to all three combinations, the rest 96 cases (50.52%) were resistant to at least one of the combinations. Susceptibility pattern of cefoperazone/sulbactam, piperacillin/tazobactam, and amoxicillin/clavulanic acid was 95.26, 92.10, and 44.31 percent respectively.. Cefoperazone/sulbactam exhibited the best activity against ESBL producing Enterobacteriaceae followed by piperacillin/tazobactam. Hospital antibiotic policies should be reviewed periodically to reduce the usage of extended spectrum cephalosporins and replace them with beta-lactam beta-lactamase inhibitor combinations agent for treating urinary tract infections.

Topics: Amoxicillin; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamase Inhibitors; Cefoperazone; Clavulanic Acids; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sensitivity and Specificity; Sulbactam; Urinary Tract Infections

Topics: Anti-Bacterial Agents; Bacteremia; Cholangitis; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination

The worldwide increase in fluoroquinolone-resistant and extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae pathogens has led to doripenem and other carbapenems assuming a greater role in the treatment of serious infections. We analyzed data from 6 phase 3 multinational doripenem clinical trials on ciprofloxacin-resistant Enterobacteriaceae isolates consisting of all genera (CIPRE) and ESBL-producing Enterobacteriaceae isolates consisting of Escherichia coli, Klebsiella spp., and Proteus spp. with ceftazidime MICs of >or=2 microg/ml (ESBLE) for prevalence by geographic region and disease type, in vitro activities of doripenem and comparator agents, and clinical or microbiologic outcomes in doripenem- and comparator-treated patients across disease types (complicated intra-abdominal infection [cIAI], complicated urinary tract infection [cUTI], and nosocomial pneumonia [NP]). Of 1,830 baseline Enterobacteriaceae isolates, 88 (4.8%) were ESBLE and 238 (13.0%) were CIPRE. The incidence of ESBLE was greatest in Europe (7.8%); that of CIPRE was higher in South America (15.9%) and Europe (14.4%). ESBLE incidence was highest in NP (12.9%) cases; that of CIPRE was higher in cUTI (18.3%) and NP (14.9%) cases. Against ESBLE and CIPRE, carbapenems appeared more active than other antibiotic classes. Among carbapenems, doripenem and meropenem were most potent. Doripenem had low MIC(90)s for CIPRE (0.5 microg/ml) and ESBLE (0.25 microg/ml). Doripenem and comparators were highly clinically effective in infections caused by Enterobacteriaceae, irrespective of their ESBL statuses. The overall cure rates were the same for doripenem (82%; 564/685) and the comparators (82%; 535/652) and similar for ESBLE (73% [16/22] versus 72% [21/29]) and CIPRE (68% [47/69] versus 52% [33/64]). These findings indicate that doripenem is an important therapeutic option for treating serious infections caused by ESBLE and CIPRE.

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; Carbapenems; Ciprofloxacin; Clinical Trials, Phase III as Topic; Doripenem; Enterobacteriaceae; Enterobacteriaceae Infections; Global Health; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prevalence

The impact of appropriate antimicrobial therapy and antimicrobial resistance on the outcome of bacteraemia due to Enterobacter spp. remains unclear. The aim of our study was to evaluate the effect of antimicrobial therapy in 377 consecutive episodes of Enterobacter bacteraemia.. This includes retrospective analysis of a prospectively collected cohort. Clinical variables recorded were age, underlying diseases, use of corticosteroids, prognosis of underlying disease according to the McCabe and Jackson criteria, source of bacteraemia, need for mechanical ventilation, empirical antibiotic treatment, definitive treatment, antimicrobial susceptibility, presentation with septic shock and 30 day mortality rate. Univariate and multivariable analyses were performed to analyse the influence of antibiotic treatment and cephalosporin resistance on mortality.. Between 1991 and 2006, 377 episodes of bacteraemia due to Enterobacter spp. (2.2%) were recorded. The frequency of Enterobacter bacteraemia significantly increased over these years. The overall mortality rate was 12.5% (47 of 377). Independent factors associated with 30 day mortality in patients with monomicrobial bacteraemia were rapidly fatal prognosis when compared with non-fatal prognosis, presentation with septic shock, patient under mechanical ventilation and unknown source of infection. The only factor independently associated with lower 30 day mortality was the empirical use of piperacillin/tazobactam.. Enterobacter spp. are an increasing cause of bacteraemia. The empirical use of piperacillin/tazobactam was independently associated with a lower 30 day mortality rate.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteremia; beta-Lactam Resistance; Enterobacter; Enterobacteriaceae Infections; Female; Humans; Male; Middle Aged; Multivariate Analysis; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prevalence; Risk Factors; Treatment Outcome

The selection of antimicrobial agents in the 2006 Guidelines (consensus statement) on Empiric Therapy for Complicated Intra-Abdominal Infections (IAIs) in Asia was based on resistance and epidemiological data from the Asian region. In these 2006 guidelines, single agent therapy using the beta-lactam/beta-lactamase inhibitors ampicillin/sulbactam or cefoperazone-sulbactam is recommended for mild-to-moderate cases, while piperacillin-tazobactam is recommended for high-severity cases. When using carbapenems, ertapenem is recommended for mild-to-moderate cases, while imipenem and meropenem are recommended for high-severity cases. For combination regimes, two types of agents are recommended: cephalosporin-based and monobactam-based. For mild-to-moderate cases, a third generation cephalosporin plus metronidazole is recommended. For high-severity cases, a third or fourth generation cephalosporin plus metronidazole+/-amikacin is recommended. For the monobactam-based regimen, aztreonam plus metronidazole is recommended for high-severity cases only.

Topics: Abdomen; Anti-Infective Agents; Asia; Bacterial Infections; beta-Lactamase Inhibitors; Consensus; Drug Resistance, Bacterial; Drug Therapy, Combination; Enterobacteriaceae; Enterobacteriaceae Infections; Fluoroquinolones; Humans; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Practice Guidelines as Topic

Receipt of a broad-spectrum cephalosporin is a strong risk factor for isolation of broad-spectrum cephalosporin-resistant Enterobacter species, and yet the risk from other broad-spectrum beta-lactams hydrolyzed by group 1 beta-lactamases has not been well characterized. We compared the risk conferred by broad-spectrum cephalosporins to that conferred by piperacillin-tazobactam, alone or in combination with an aminoglycoside or a fluoroquinolone. A retrospective cohort was monitored from treatment onset until a broad-spectrum cephalosporin-resistant Enterobacter strain was isolated or the patient was discharged. There were 447 patients in the piperacillin-tazobactam group and 2,341 patients in the broad-spectrum cephalosporin group. Groups were similar in age (mean, 62.5 years). The piperacillin-tazobactam group had a smaller percentage of men (32% versus 44%, P < 0.001) and a lower rate of intensive care unit stay (25% versus 38%, P < 0.001) but a higher rate of surgery (41% versus 26%, P < 0.001). Groups differed in the distribution of comorbidities. Resistant Enterobacter strains were isolated from 62 patients, 2% in each group (hazard ratio [RR] = 1.02 [P = 0.95]). In multivariable analysis, risk was similar among treatment groups (RR = 0.71 [P = 0.32]). Intensive care unit stay and surgery were associated with increased risk (RR = 4.53 [P < 0.001] and RR = 1.97 [P = 0.015], respectively), fluoroquinolones were protective (RR = 0.24 [P = 0.003]), and aminoglycosides did not affect risk (RR = 0.98 [P = 0.95]). The protective effect of fluoroquinolones against isolation of broad-spectrum cephalosporin-resistant Enterobacter spp. and the equivalence in risk associated with piperacillin-tazobactam and broad-spectrum cephalosporins may have important clinical and epidemiologic implications.

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; Ceftazidime; Ceftriaxone; Cohort Studies; Drug Therapy, Combination; Enterobacter; Enterobacteriaceae Infections; Female; Humans; Male; Middle Aged; Multivariate Analysis; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Proportional Hazards Models; Retrospective Studies; Risk Factors