piperacillin--tazobactam-drug-combination and Sepsis

Topics: Anti-Bacterial Agents; Carbapenems; Humans; Intraabdominal Infections; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Sepsis

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

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

Insufficient antimicrobial exposure is associated with worse outcomes in sepsis. We evaluated whether therapeutic drug monitoring (TDM)-guided antibiotic therapy improves outcomes.. Randomized, multicenter, controlled trial from January 2017 to December 2019. Adult patients (n = 254) with sepsis or septic shock were randomly assigned 1:1 to receive continuous infusion of piperacillin/tazobactam with dosing guided by daily TDM of piperacillin or continuous infusion with a fixed dose (13.5 g/24 h if eGFR ≥ 20 mL/min). Target plasma concentration was four times the minimal inhibitory concentration (range ± 20%) of the underlying pathogen, respectively, of Pseudomonas aeruginosa in empiric situation. Primary outcome was the mean of daily total Sequential Organ Failure Assessment (SOFA) score up to day 10.. Among 249 evaluable patients (66.3 ± 13.7 years; female, 30.9%), there was no significant difference in mean SOFA score between patients with TDM (7.9 points; 95% CI 7.1-8.7) and without TDM (8.2 points; 95% CI 7.5-9.0) (p = 0.39). Patients with TDM-guided therapy showed a lower 28-day mortality (21.6% vs. 25.8%, RR 0.8, 95% CI 0.5-1.3, p = 0.44) and a higher rate of clinical (OR 1.9; 95% CI 0.5-6.2, p = 0.30) and microbiological cure (OR 2.4; 95% CI 0.7-7.4, p = 0.12), but these differences did not reach statistical significance. Attainment of target concentration was more common in patients with TDM (37.3% vs. 14.6%, OR 4.5, CI 95%, 2.9-6.9, p < 0.001).. TDM-guided therapy showed no beneficial effect in patients with sepsis and continuous infusion of piperacillin/tazobactam with regard to the mean SOFA score. Larger studies with strategies to ensure optimization of antimicrobial exposure are needed to definitively answer the question.

Topics: Adult; Anti-Bacterial Agents; Drug Monitoring; Female; Humans; Multiple Organ Failure; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sepsis

The aim of this study was to emulate the MERINO trial of piperacillin-tazobactam vs meropenem for the definitive treatment of bloodstream infection (BSI) caused by ceftriaxone-nonsusceptible E coli or Klebsiella spp.. Data from an observational study of BSI and a randomised controlled trial of a rapid diagnostic in BSI were used to emulate the MERINO trial. The primary outcome of the emulated trial was 28-day mortality after blood culture. Outcomes were compared using logistic regression adjusted for propensity score for emulated intervention.. Of the 6,371 observational study and RCT participants, 1,968 had a bloodstream infection with E. coli or Klebsiella spp. of which 121 met the eligibility criteria. In the emulated trial, a total of 14/82 patients (17.1%) allocated to piperacillin-tazobactam met the primary outcome compared with 6/39 (15.4%) in the meropenem group (unadjusted odds ratio 1.13 (95% CI 0.40 to 3.21)). After adjustment for propensity score, the odds ratio increased to 1.31 (95% CI 0.40 to 4.26). This difference is in the same direction but of a smaller magnitudethan observed in the MERINO trial, where 30-day mortality was met by 23/187 patients (12.3%) in the piperacillin-tazobactam and 7/191 (3.7%) in the meropenem group (unadjusted odds ratio of 3.69 (95% CI 1.48 to 10.41)).. The mortality rate in an emulated trial population was more than double the mortality rate in the MERINO trial. The methodology used attempts to address the concern that previous results could be explained by biases such as selection bias and uncontrolled confounding and provides information on how a trial such as the MERINO trial may have performed in the NHS.

Topics: Anti-Bacterial Agents; Escherichia coli; Humans; Meropenem; Piperacillin, Tazobactam Drug Combination; Sepsis

Bloodstream infections (BSIs) adversely affect clinical outcome in children with cancer. Over 1 decade, this retrospective cohort study describes pathogen distribution in BSIs and antimicrobial susceptibility against empirical antibiotics frequently prescribed in children with cancer. The antibiotic efficacy was evaluated through the determination of minimal inhibitory concentrations for piperacillin-tazobactam and meropenem and by disk diffusion for remaining antibiotics. From 2004 to 2013, 398 BSIs occurred in 196 children with cancer (median age: 5.4 y), resulting in 457 bacteria. Overall, 266 (58.2%) were Gram-positive, and 191 (41.8%) were Gram-negative with a significant Gram-positive increase over time (P=0.032). Coagulase-negative staphylococci (74, 16.2%), viridans group streptococci (67, 14.7%), Escherichia coli (52, 11.4%), and Staphylococcus aureus (39, 8.5%) were the most common pathogens. Susceptibility to piperacillin-tazobactam (95.9%, P=0.419) and meropenem (98.9%, P=0.752) was stable over time, and resistance was observed among viridans group streptococci against piperacillin-tazobactam (18%) and meropenem (7%) and among Enterobacterales against piperacillin-tazobactam (3%). Vancomycin showed 98% Gram-positive activity, gentamicin 82% Gram-negative activity and ampicillin, cefotaxime, and cefuroxime were active in 50%, 72%, and 69% of pathogens, respectively, and BSI-related mortality was 0%. In conclusion, over 1 decade, we report an increase in Gram-positive BSIs, and stable, low-resistance rates against currently recommended empirical antibiotics, piperacillin-tazobactam and meropenem.

Topics: Adolescent; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Male; Meropenem; Microbial Sensitivity Tests; Neoplasms; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Sepsis

β-Lactam antibiotics display a time-dependent mechanism of action, with evidence suggesting improved outcomes when administering these drugs via continuous infusion compared with standard intermittent infusion. However, there is no phase 3 randomised controlled trial (RCT) evidence to support one method of administration over another in critically ill patients with sepsis.. The β-Lactam Infusion Group (BLING) III study is a prospective, multicentre, open, phase 3 RCT to compare continuous infusion with standard intermittent infusion of β-lactam antibiotics in critically ill patients with sepsis. The study will be conducted in about 70 intensive care units (ICUs) in Australia, New Zealand, the United Kingdom, Belgium and selected other countries, from 2018 to 2021.. BLING III will recruit 7000 critically ill patients with sepsis being treated with one of two β-lactam antibiotics (piperacillin-tazobactam or meropenem) to receive the β-lactam antibiotic by either continuous or intermittent infusion.. The primary outcome is allcause mortality within 90 days after randomisation. Secondary outcomes are clinical cure at Day 14 after randomisation, new acquisition, colonisation or infection with a multiresistant organism or Clostridium difficile diarrhoea up to 14 days after randomisation, all-cause ICU mortality and all-cause hospital mortality. Tertiary outcomes are ICU length of stay, hospital length of stay and duration of mechanical ventilation and duration of renal replacement therapy up to 90 days after randomisation.. The BLING III study will compare the effect on 90-day mortality of β-lactam antibiotics administered via continuous versus intermittent infusion in 7000 critically ill patients with sepsis.. ClinicalTrials.gov Registry (NCT03213990).

Topics: Anti-Bacterial Agents; Australia; beta-Lactams; Critical Illness; Drug Administration Schedule; Humans; Infusions, Intravenous; Meropenem; New Zealand; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Sepsis; Treatment Outcome; United Kingdom

Piperacillin-tazobactam is commonly used in neutropenic sepsis at standard doses that do not account for inter-individual differences in age, bodyweight and renal function. This study was designed to assess the rate of attainment of pharmacokinetic/pharmacodynamic (PK/PD) targets in patients receiving piperacillin/tazobactam therapy and to evaluate the effect on clinical outcomes.. Patients undergoing intensive chemotherapy for aggressive hematological malignancies were enrolled and treated with piperacillin/tazobactam 4 g/0.5 g every 6 h as initial antimicrobial therapy for first fever. Plasma drug concentrations were assayed at 50% and 100% of the dosing interval and compared with target MIC breakpoint of 16 mg/L to calculate the primary endpoints of 50% and 100% time above MIC (fT > MIC), respectively. Secondary endpoints included time to clinical cure, length of hospital stay, duration of antibiotics, and clinical treatment success.. Fifty-eight percent (14/24) of patients achieved 50% fT > MIC while only 4% (1/24) achieved 100% fT > MIC. Higher creatinine clearance was significantly associated with lower trough drug concentration and appeared to be the dominant reason for the poor PK/PD target attainment. Median time to clinical cure, duration of antibiotic therapy, and hospital length of stay was 3, 13 and 21 days, respectively. There were no statistically significant differences in these outcomes between patients who did and did not achieve 100% fT > MIC.. A significant majority of febrile neutropenic patients fail to achieve PK/PD targets with 6-hourly piperacillin dosing, although the clinical implications of this finding are unclear. Larger studies are needed to assess any impact on morbidity and mortality. This trial is registered on the ANZCTR (ACTRN12618000110280).

Topics: Adult; Aged; Anti-Bacterial Agents; Antineoplastic Agents; Chemotherapy-Induced Febrile Neutropenia; Female; Hematologic Neoplasms; Humans; Length of Stay; Male; Microbial Sensitivity Tests; Middle Aged; Piperacillin, Tazobactam Drug Combination; Sepsis; Time Factors; Treatment Outcome

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection with a hospital mortality in excess of 40%. Along with insufficient and delayed empirical antimicrobial therapy, inappropriate antimicrobial exposure has been identified to negatively affect patient outcomes. Receipt of prolonged infusion (i.e. extended or continuous infusion) of piperacillin/tazobactam (TZP) improves antimicrobial exposure and is associated with reduced mortality in patients with sepsis. Using therapeutic drug monitoring (TDM) with dosing tailored to the altered pharmacokinetics of the individual patient to avoid under- and overdosing may be a further strategy to improve patient outcomes. This current trial will address the question whether a TDM-guided therapy with TZP administered by continuous infusion will result in a greater resolution of organ dysfunction and hence better clinical outcome compared to continuous infusion of the total daily dose of TZP without TDM.. The study is an investigator-initiated, multi-centre, parallel-group, single-blinded, randomised controlled trial. The trial will be conducted in several centres across Germany. Adult patients (aged ≥ 18 years) with severe sepsis or septic shock will be eligible for study participation. Participants will be randomly assigned to receive either TZP by continuous infusion guided by daily TDM of piperacillin (experimental group) or by continuous infusion without TDM guidance (total daily dose in normal renal function 13.5 g TZP) (control group). The pharmacokinetic (PK)/pharmacodynamic (PD) target will be 100% f T. This trial will assess for the first time whether continuous infusion of TZP guided by daily TDM in patients with sepsis will result in a greater resolution of organ dysfunction and hence better clinical outcome compared to continuous infusion without TDM.. German Clinical Trials Register (GermanCTR), DRKS00011159 . Registered on 10 October 2016.

Topics: Anti-Bacterial Agents; Drug Administration Schedule; Drug Monitoring; Germany; Humans; Infusions, Parenteral; Multicenter Studies as Topic; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Randomized Controlled Trials as Topic; Sepsis; Time Factors; Treatment Outcome

The objective of the study was to evaluate the effect of administering prophylactic antibiotics on the development of neonatal sepsis in term neonates born through meconium-stained amniotic fluid (MSAF). Two hundred and fifty eligible neonates were randomized to study group (Antibiotic group-receiving first-line antibiotics for 3 days) and control group (No Antibiotic group). Both groups were evaluated clinically and by laboratory parameters (sepsis screen and blood cultures) for development of sepsis. All neonates were monitored for respiratory, neurological, and other systemic complications and received supportive treatment according to standard management protocol of the unit. One hundred and twenty one neonates were randomized to 'Antibiotic' group and 129 to 'No Antibiotic' group. The overall incidence of suspect sepsis was 9.6 % in the study population with no significant difference between 'No Antibiotic' and 'Antibiotic' groups (10.8 vs. 8.2 %, p = 0.48, odds ratio (OR) 0.74, 95 % confidence interval (CI) 0.32-1.73). Incidence of culture-proven sepsis was also not significantly different between the two groups (5.42 vs. 4.13 %, p = 0.63, OR 0.75, 95 % CI 0.23-2.43). The incidence of mortality, meconium aspiration syndrome, and other complications was comparable amongst the two groups.. Routine antibiotic prophylaxis in neonates born through MSAF did not reduce the incidence of sepsis in this study population. (Clinicaltrials.gov no. - NCT01290003).

Topics: Amikacin; Amniotic Fluid; Anti-Bacterial Agents; Antibiotic Prophylaxis; Double-Blind Method; Female; Humans; Infant, Newborn; Infusions, Intravenous; Male; Meconium; Meconium Aspiration Syndrome; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pregnancy; Prospective Studies; Sepsis

Neonates at risk for early-onset sepsis are started on antibiotics empirically. Antibiotic resistance to conventionally used antibiotics is increasingly being reported. Antenatal maternal antibiotic exposure in this setting contributes to low yield on blood culture drawn at birth, limiting the planning of antibiotics based on culture reports. A head-to-head comparison for selecting the appropriate antibiotic is one strategy.. To compare monotherapy with amikacin against piperacillin-tazobactum as an empirical therapy in neonates at risk for early-onset sepsis.. Randomized open-label controlled trial with stratification and block randomization.. Tertiary care neonatal unit in India. All consecutive inborn neonates delivered between 01 May 2009 and 30 April 2011 who were ≥28 week gestation and/or ≥1000 g birth weight with risk factors for early-onset sepsis.. Randomized to receive either amikacin or piperacillin-tazobactum, after stratifying as asymptomatic or symptomatic within 1 h of birth.. Incidence of treatment failure to the allocated antibiotic defined as blood culture isolate reported resistant to the allocated antibiotic or progression of the illness, necessitating a change of antibiotic.. Of 204 eligible cases, 187 were enrolled. Seventeen babies were excluded. A total of 128 neonates were stratified as asymptomatic and 59 as symptomatic. In all, 64 of the asymptomatic cases received amikacin and 64 received piperacillin-tazobactum, while 29 symptomatic babies received amikacin and 30 received piperacillin-tazobactum. Five babies had blood culture-positive sepsis, and 28 babies had strong suspicion of sepsis. There was no difference in the treatment failure in the amikacin group (3 of 93; 3.2%) compared with piperacillin-tazobactum group (2 of 94; 2.1%) (p > 0.01) and no difference in the incidence of second infection, fungal sepsis and all-cause mortality at day 7 and 28 between the two study groups (p > 0.01).. Monotherapy with amikacin as an empirical antibiotic did not result in a higher incidence of treatment failure in neonates at risk for early-onset sepsis as compared with piperacillin-tazobactum. Both antibiotics were effective in management of babies with early-onset sepsis.

Topics: Amikacin; Anti-Bacterial Agents; Bacterial Infections; Drug Therapy, Combination; Female; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; India; Infant, Newborn; Male; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Risk Factors; Sepsis; Treatment Outcome

The effect of different antibiotics on the outcome of surgical care in the management of diabetic foot was investigated. We randomly allocated 100 patients with diabetic foot into one of four groups. Each patient's infection was graded (Wagner classification). All patients were offered the same surgical care but each group was assigned a different antibiotic. Hospital stay for the four groups ranged from 7 to 14 days. Five patients experienced complications from septicaemia; 15 patients underwent amputation; and five patients experienced temporary renal impairment. Careful consideration to the type of antibiotic used is essential.

Topics: Amikacin; Amputation, Surgical; Anti-Bacterial Agents; Ceftazidime; Chemotherapy, Adjuvant; Debridement; Diabetic Foot; Drug Combinations; Drug Monitoring; Humans; Imipenem; Kidney Diseases; Length of Stay; Lincomycin; Metronidazole; Patient Selection; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sepsis; Severity of Illness Index; Treatment Outcome; Wound Healing; Wound Infection

Piperacillin/tazobactam (P/T) was used in the treatment of 40 patients at the age of 22 to 64 years with intraabdominal infection (peritonitis, abscesses). P/T was administered as 30-minute intravenous infusions 4 or 3 times a day for 3 to 13 days. The recovery and improvement were stated in 80 and 10 per cent of the cases respectively. In 10 per cent of the patients the treatment failed because of surgical complications or insufficient surgical intervention or because of some other systemic diseases. The pathogens in the abdominal cavity were eradicated in 31 cases. In 5 cases the pathogen eradication was followed by superinfection. No relapses or pathogen persistence were recorded. Only in 1 case Edwardsiella tarda strains resistant to P/T were isolated from the abdominal cavity discharge and P/T resistant Aeromonas hydrophila strains from the urine by the 3rd or the 5th day of the treatment. The results are in favour of P/T as a drug of choice in the treatment of surgical patients with abdominal sepsis.

Topics: Abdominal Abscess; Adult; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Penicillanic Acid; Peritonitis; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sepsis

Topics: Anti-Bacterial Agents; Emergency Service, Hospital; Humans; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Sepsis

There is a paucity of published data to evaluate the efficacy and safety of imipenem, cefepime and piperacillin/tazobactam dosing regimens against bloodstream infections caused by Klebsiella aerogenes (BSIs-Kae) and Enterobacter cloacae complex (BSIs-Ecc) in patients with various degrees of renal function.. Pathogens were isolated from China's blood bacterial resistant investigation network. The dosing regimens of imipenem, cefepime and piperacillin were simulated with intermittent infusion and extended infusion. Monte Carlo simulation was performed to calculate the probability of target attainment and a cumulative fraction of response (CFR) against BSIs-Kae/Ecc.. Cefepime, not piperacillin/tazobactam, can be a reasonable carbapenem-sparing option in empirically treating BSIs-Kae/Ecc.

Topics: Anti-Bacterial Agents; Cefepime; Enterobacter; Humans; Imipenem; Microbial Sensitivity Tests; Monte Carlo Method; Piperacillin, Tazobactam Drug Combination; Sepsis

To evaluate the association between early and cumulative beta-lactam pharmacokinetic/pharmacodynamic (PK/PD) parameters and therapy outcomes in bloodstream infection (BSI).. Early and cumulative achievement of fT

Topics: Adult; Anti-Bacterial Agents; beta-Lactams; Critical Illness; Humans; Meropenem; Microbial Sensitivity Tests; Middle Aged; Piperacillin, Tazobactam Drug Combination; Sepsis

Delay to first antibiotic dose in patients with sepsis has been associated with increased mortality. Second dose antibiotic delay has also been linked to worsened patient outcomes. Optimal methods to decrease second dose delay are currently unclear. The primary objective of this study was to evaluate the association between updating an emergency department (ED) sepsis order set design from one-time doses to scheduled antibiotic frequencies and delay to administration of second piperacillin-tazobactam dose.. This retrospective cohort study was conducted at eleven hospitals in a large, integrated health system and included adult patients treated in the ED with at least one dose of piperacillin-tazobactam ordered through an ED sepsis order set over a two year period. Patients were excluded if they received less than two doses of piperacillin-tazobactam. Midway through the study period, the enterprise-wide ED sepsis order set was updated to include scheduled antibiotic frequencies. Two patient cohorts receiving piperacillin-tazobactam were compared: those in the year before the order set update and those in the year post-update. The primary outcome was major delay, defined as an administration delay >25% of the recommended dosing interval, which was evaluated with multivariable logistic regression and interrupted time series analysis.. 3219 patients were included: 1222 in the pre-update group and 1997 in the post-update group. The proportion of patients who experienced major second dose delay was significantly lower in the post-update group (32.7% vs 25.6%, p < 0.01; adjusted OR 0.64, 95% CI 0.52 to 0.78). No between-group difference was detected in the slope of monthly major delay frequency, but there was a significant level change (post-update change -10%, 95% CI -17.9% to -1.9%).. Including scheduled antibiotic frequencies in ED sepsis order sets is a pragmatic mechanism to decrease delays in second antibiotic doses.

Topics: Adult; Anti-Bacterial Agents; Emergency Service, Hospital; Humans; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Sepsis; Tazobactam

Despite improvements in perioperative mortality, the incidence of postoperative surgical site infection (SSI) remains high after pancreatoduodenectomy. The effect of broad-spectrum antimicrobial surgical prophylaxis in reducing SSI is poorly understood.. To define the effect of broad-spectrum perioperative antimicrobial prophylaxis on postoperative SSI incidence compared with standard care antibiotics.. Pragmatic, open-label, multicenter, randomized phase 3 clinical trial at 26 hospitals across the US and Canada. Participants were enrolled between November 2017 and August 2021, with follow-up through December 2021. Adults undergoing open pancreatoduodenectomy for any indication were eligible. Individuals were excluded if they had allergies to study medications, active infections, chronic steroid use, significant kidney dysfunction, or were pregnant or breastfeeding. Participants were block randomized in a 1:1 ratio and stratified by the presence of a preoperative biliary stent. Participants, investigators, and statisticians analyzing trial data were unblinded to treatment assignment.. The intervention group received piperacillin-tazobactam (3.375 or 4 g intravenously) as perioperative antimicrobial prophylaxis, while the control group received cefoxitin (2 g intravenously; standard care).. The primary outcome was development of postoperative SSI within 30 days. Secondary end points included 30-day mortality, development of clinically relevant postoperative pancreatic fistula, and sepsis. All data were collected as part of the American College of Surgeons National Surgical Quality Improvement Program.. The trial was terminated at an interim analysis on the basis of a predefined stopping rule. Of 778 participants (378 in the piperacillin-tazobactam group [median age, 66.8 y; 233 {61.6%} men] and 400 in the cefoxitin group [median age, 68.0 y; 223 {55.8%} men]), the percentage with SSI at 30 days was lower in the perioperative piperacillin-tazobactam vs cefoxitin group (19.8% vs 32.8%; absolute difference, -13.0% [95% CI, -19.1% to -6.9%]; P < .001). Participants treated with piperacillin-tazobactam, vs cefoxitin, had lower rates of postoperative sepsis (4.2% vs 7.5%; difference, -3.3% [95% CI, -6.6% to 0.0%]; P = .02) and clinically relevant postoperative pancreatic fistula (12.7% vs 19.0%; difference, -6.3% [95% CI, -11.4% to -1.2%]; P = .03). Mortality rates at 30 days were 1.3% (5/378) among participants treated with piperacillin-tazobactam and 2.5% (10/400) among those receiving cefoxitin (difference, -1.2% [95% CI, -3.1% to 0.7%]; P = .32).. In participants undergoing open pancreatoduodenectomy, use of piperacillin-tazobactam as perioperative prophylaxis reduced postoperative SSI, pancreatic fistula, and multiple downstream sequelae of SSI. The findings support the use of piperacillin-tazobactam as standard care for open pancreatoduodenectomy.. ClinicalTrials.gov Identifier: NCT03269994.

Topics: Adult; Aged; Anti-Bacterial Agents; Cefoxitin; Humans; Male; Pancreatic Fistula; Pancreaticoduodenectomy; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sepsis; Surgical Wound Infection

As causative pathogens are not usually identified at the time of initiating antibiotics in sepsis, carbapenems are commonly used as an initial treatment. To reduce indiscriminate use of carbapenems, the efficacy of alternative empiric regimens, such as piperacillin-tazobactam and the fourth-generation cephalosporins, should be elucidated. This study aimed to evaluate survival effect associated with carbapenems as initial therapy for sepsis compared with these antibiotics.. Multicenter retrospective observational study.. Tertiary hospitals in Japan.. Adult patients diagnosed as having sepsis from 2006 to 2019.. Administration of carbapenems as initial antibiotic therapy.. This study used data of adult patients with sepsis extracted from a large-scale database in Japan. Patients were divided into two groups as follows: patients receiving carbapenems and patients receiving noncarbapenem broad-spectrum beta-lactam antibiotics as initial treatment. In-hospital mortality was compared between the groups by a logistic regression model adjusted by an inverse probability treatment weighting using propensity scores. To evaluate heterogeneity of effects according to patient characteristics, we also fitted logistic models in several subgroups. Among 7,392 patients with sepsis, 3,547 patients received carbapenems, and 3,845 patients received noncarbapenem agents. The logistic model showed no significant association between carbapenem therapy and lower mortality (adjusted OR 0.88, p = 0.108). Subgroup analyses suggested that there were significant survival benefits associated with carbapenem therapy in patients with septic shock, in ICUs, or with mechanical ventilation ( p for effect modifications: < 0.001, 0.014, and 0.105, respectively).. Compared with the noncarbapenem broad-spectrum antibiotics, carbapenems as an initial therapy for sepsis were not associated with significantly lower mortality.

Topics: Adult; Anti-Bacterial Agents; Carbapenems; Hospital Mortality; Humans; Monobactams; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Sepsis; Treatment Outcome

Carbapenems (CR) have traditionally been the first line treatment for bacteremia caused by AmpC-producing Enterobacterales. However, CR have a high ecological impact, and carbapenem-resistant strains continue rising. Thus, other treatment alternatives like Piperacillin-Tazobactam (P-T) or Cefepime (CEF) and oral sequential therapy (OST) are being evaluated.. We conducted a retrospective, single-centre observational study. All adult patients with AmpC-producing Enterobacterales bacteremia were included. The primary endpoint was clinical success defined as a composite of clinical cure, 14-day survival, and no adverse events. We evaluated the evolution of patients in whom OST was performed.. Seventy-seven patients were included, 22 patients in the CR group and 55 in the P-T/CEF group (37 patients received CEF and 18 P-T). The mean age of the patients was higher in the P-T/CEF group (71 years in CR group vs. 76 years in P-T/CEF group, p = 0.053). In the multivariate analysis, age ≥ 70 years (OR 0.08, 95% CI [0.007-0.966], p = 0.047) and a Charlson index ≥ 3 (OR 0.16, 95% CI [0.026-0.984], p = 0.048), were associated with a lower clinical success. Treatment with P-T/CEF was associated with higher clinical success (OR 7.75, 95% CI [1.273-47.223], p = 0.026). OST was performed in 47% of patients. This was related with a shorter in-hospital stay (OST 14 days [7-22] vs. non-OST 18 days [13-38], p = 0.005) without difference in recurrence (OST 3% vs. non-OST 5%, p = 0.999).. Targeted treatment with P-T/CEF and OST could be safe and effective treatments for patients with AmpC-producing Enterobacterales bacteremia.

Topics: Adult; Aged; Bacteremia; Carbapenems; Cefepime; Humans; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Sepsis

Knowledge on the tissue penetration of piperacillin-tazobactam in children with sepsis is lacking. In this study, the feasibility and performance of microdialysis experiments were explored in septic piglets and children as part of a translational research project.. Multiple-day microdialysis investigations were performed in muscle tissue of 22 piglets (of which 11 were septic) and 6 children with sepsis. An in vitro experiment preceded the (pre)clinical trials to derive optimal experimental settings and calibration technique. Linear mixed-effects models quantified the impact of sepsis on relative recovery (RR) and intercatheter, interindividual, interoccasion, and residual variability.. In vivo microdialysis was well tolerated in piglets and children, with no significant adverse events reported. Using identical experimental settings, lower RR values were recorded in healthy and septic piglets (range: piperacillin, 17.2-29.1% and tazobactam, 23.5-29.1%) compared with the in vitro experiment (piperacillin, 43.3% and tazobactam, 55.3%), and there were unacceptably low values in children with sepsis (<10%). As a result, methodological changes were made in the pediatric trial. Realistic tissue concentration-time curves were derived in piglets and children. In piglets, sepsis reduced the RR. The greatest contributors to RR variability were residual (>40%) and interoccasion (>30%) variability. The internal standard method was the preferred calibration technique in both piglets and children.. Microdialysis is a safe and applicable method for the measurement of tissue drug concentrations in piglets and children. This study demonstrated the impact of experimental settings, sepsis, and target population on individual RR.

Topics: Animals; Anti-Bacterial Agents; Child; Humans; Microdialysis; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sepsis; Swine; Tazobactam

Cefepime and piperacillin-tazobactam are commonly administered to hospitalized adults for empirical treatment of infection. Although piperacillin-tazobactam has been hypothesized to cause acute kidney injury and cefepime has been hypothesized to cause neurological dysfunction, their comparative safety has not been evaluated in a randomized clinical trial.. To determine whether the choice between cefepime and piperacillin-tazobactam affects the risks of acute kidney injury or neurological dysfunction.. The Antibiotic Choice on Renal Outcomes (ACORN) randomized clinical trial compared cefepime vs piperacillin-tazobactam in adults for whom a clinician initiated an order for antipseudomonal antibiotics within 12 hours of presentation to the hospital in the emergency department or medical intensive care unit at an academic medical center in the US between November 10, 2021, and October 7, 2022. The final date of follow-up was November 4, 2022.. Patients were randomized in a 1:1 ratio to cefepime or piperacillin-tazobactam.. The primary outcome was the highest stage of acute kidney injury or death by day 14, measured on a 5-level ordinal scale ranging from no acute kidney injury to death. The 2 secondary outcomes were the incidence of major adverse kidney events at day 14 and the number of days alive and free of delirium and coma within 14 days.. There were 2511 patients included in the primary analysis (median age, 58 years [IQR, 43-69 years]; 42.7% were female; 16.3% were Non-Hispanic Black; 5.4% were Hispanic; 94.7% were enrolled in the emergency department; and 77.2% were receiving vancomycin at enrollment). The highest stage of acute kidney injury or death was not significantly different between the cefepime group and the piperacillin-tazobactam group; there were 85 patients (n = 1214; 7.0%) in the cefepime group with stage 3 acute kidney injury and 92 (7.6%) who died vs 97 patients (n = 1297; 7.5%) in the piperacillin-tazobactam group with stage 3 acute kidney injury and 78 (6.0%) who died (odds ratio, 0.95 [95% CI, 0.80 to 1.13], P = .56). The incidence of major adverse kidney events at day 14 did not differ between groups (124 patients [10.2%] in the cefepime group vs 114 patients [8.8%] in the piperacillin-tazobactam group; absolute difference, 1.4% [95% CI, -1.0% to 3.8%]). Patients in the cefepime group experienced fewer days alive and free of delirium and coma within 14 days (mean [SD], 11.9 [4.6] days vs 12.2 [4.3] days in the piperacillin-tazobactam group; odds ratio, 0.79 [95% CI, 0.65 to 0.95]).. Among hospitalized adults in this randomized clinical trial, treatment with piperacillin-tazobactam did not increase the incidence of acute kidney injury or death. Treatment with cefepime resulted in more neurological dysfunction.. ClinicalTrials.gov Identifier: NCT05094154.

Topics: Acute Kidney Injury; Adult; Anti-Bacterial Agents; Cefepime; Coma; Delirium; Drug Therapy, Combination; Female; Humans; Kidney; Male; Middle Aged; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Sepsis

Late-onset sepsis is common in extremely low birth weight (ELBW) infants, and it leads to the use of antibiotics to cover resistant organisms, which can be nephrotoxic. Here we have investigated the role of vancomycin plus piperacillin-tazobactam on the rate of acute kidney injury (AKI).. In a retrospective case-control study, medical records of all ELBW infants who were admitted to our Neonatal Intensive Care Unit (NICU) with late onset sepsis who were prescribed vancomycin plus piperacillin-tazobactam were reviewed for demographics, clinical characteristics, use of potential nephrotoxic medications and outcomes.. During the study period, 264 patients were admitted, of whom 28.4%(75/264) received vancomycin plus piperacillin-tazobactam and were matched with 64 controls. There were no differences in gestational age or birth weight between cases and controls [688±160 vs. 689±162 grams (p = 0.99), and 24.7±1.8 vs. 24.7±1.6 weeks (p = 0.99) respectively]. There was no difference in the rate of sepsis between cases and controls [76%(55/72) vs. 64%(41/64) respectively, p = 0.11]. Infants exposed to vancomycin plus piperacillin-tazobactam had a higher percentage of concomitant use of vasopressors and amphotericin. To adjust for confounders, a logistic regression analysis was conducted with AKI as the dependent variable. Use of vasopressors and vancomycin plus piperacillin-tazobactam were the only risk factors associated with AKI with an adjusted OR (95%CI) of 4.08 (1.90-8.74), p < 0.001; and 2.87 (1.26-6.53), p = 0.01 respectively.. The use of vancomycin plus piperacillin-tazobactam in ELBW infants is associated with an increased risk for AKI.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Case-Control Studies; Drug Therapy, Combination; Female; Humans; Infant, Extremely Low Birth Weight; Infant, Newborn; Male; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Sepsis; Vancomycin

Topics: Anti-Bacterial Agents; Drug Monitoring; Drug Therapy, Combination; Humans; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sepsis

Topics: Anti-Bacterial Agents; Drug Monitoring; Drug Therapy, Combination; Humans; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sepsis

Topics: Anti-Bacterial Agents; Humans; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sepsis

Vancomycin plus piperacillin-tazobactam (VPT) is a commonly used antimicrobial regimen for septic patients. VPT is more nephrotoxic than other regimens such as vancomycin plus cefepime (VC) when given over several days. This risk of nephrotoxicity is less clear when VPT is given for initial empiric therapy in sepsis and de-escalated quickly based on evolving clinical information. The objective of this study was to assess nephrotoxicity among septic patients empirically treated with either VPT or VC at initial clinical presentation. We conducted a retrospective study of septic patients who received VPT or VC within 12 h of presentation to the emergency department. The primary outcomes were acute kidney injury (AKI) and renal recovery 72 h after presentation. For the total of 418 patients, 306 received VPT and 112 received VC. Rates of AKI at 72 h were 15.2% for VPT patients and 11.0% for VC patients [p = 0.44]. Among patients with AKI at presentation, 16.3% of VPT patients had AKI at 72 h compared to 8.9% of VC patients [p = 0.19]. Among those without AKI at presentation, 14.2% VPT patients and 16.7% VC patients had AKI at 72 h [p = 0.71]. Renal recovery rates for patients with AKI at presentation were 42.3% for VPT patients versus 40.3% for VC patients [p = 0.78]. In-hospital renal replacement therapy occurred in 6.2% VPT patients and 0.9% VC patients [p = 0.024]. Therefore, initial empiric therapy with VPT in sepsis may not confer increased risk of AKI when de-escalated appropriately.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Cefepime; Drug Therapy, Combination; Female; Humans; Male; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Sepsis; Vancomycin

Early-onset sepsis (EOS) is a common disease in neonates with a high morbidity and mortality rate. Piperacillin/tazobactam has been used extensively and empirically for EOS treatment without clinically validated dosing regimens, although the population pharmacokinetics (PPK) of piperacillin in neonates has been reported. Therefore, we wanted to study the effectiveness and tolerance of a PPK model-based dosing regimen of piperacillin/tazobactam in EOS patients.. A prospective, single-centre, phase II clinical study of piperacillin/tazobactam in neonates with EOS was conducted. The dosing regimen (90 mg·kg. A total of 52 neonates were screened and 49 neonates completed their piperacillin/tazobactam treatment course and were included in this analysis. The median (range) values of postmenstrual age were 33.57 (range 26.14-41.29) weeks. Forty-seven (96%) neonates reached their PD target. Eight (16%) neonates experienced treatment failure clinically. The mean (SD, range) duration of treatment and length of hospitalization were 100.1 (62.2, 36.2-305.8) hours and 31 (30, 5-123) days. There were no obvious adverse events and no infection-related deaths occurred in the first month of life.. A model-based dosing regimen of piperacillin/tazobactam was evaluated clinically, was tolerated well and was determined to be effective for EOS treatment.

Topics: Anti-Bacterial Agents; Humans; Infant; Infant, Newborn; Microbial Sensitivity Tests; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Sepsis

In the treatment of septic patients, the prediction of a pathogen's susceptibility to piperacillin

Topics: Anti-Bacterial Agents; Escherichia coli; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Klebsiella pneumoniae; Microbial Sensitivity Tests; Piperacillin, Tazobactam Drug Combination; Pseudomonas aeruginosa; Reproducibility of Results; Sepsis

The SEP-1 measures have tied financial reimbursement to the treatment of patients with severe sepsis and septic shock. The purpose of this study was to assess the impact of a SEP-1 initiative on the utilization of broad-spectrum combination therapy (BSCT) in the emergency department (ED).. This was an IRB-approved, retrospective evaluation of adult patients who received vancomycin plus an antipseudomonal beta-lactam for a urinary tract infection (UTI) or skin or soft tissue infection (SSTI) in the ED. The primary outcome was the proportion of patients in which use of BSCT was considered appropriate based on clinical criteria. Secondary outcomes included door to antibiotic order time, door to administration time, proportion of patients continued on BSCT upon admission, duration of BSCT, and in-hospital mortality.. A total of 400 patients were included in the analysis. Following SEP-1 implementation, appropriate use of BSCT decreased by 12%, with 54% of patients in the pre-SEP-1 group meeting clinical criteria compared to 42% in the post-SEP-1 group (p = 0.028). In the subgroup of patients with a suspected UTI the appropriate use of BSCT declined by 25% (40% vs 15%, p = 0.005). The median door to first antibiotic administration time was not significantly different between groups (63 min vs 61 min, p = 0.091).. The implementation of the SEP-1 mandated measures was associated with an increase in the unnecessary use of BSCT. Additionally, no difference was seen in time to antibiotic administration. The results of this study demonstrate the negative impact that the SEP-1 mandate may have on antimicrobial utilization within the ED.

Topics: Adult; Aged; Anti-Bacterial Agents; Aztreonam; beta-Lactams; Cefepime; Centers for Medicare and Medicaid Services, U.S.; Early Diagnosis; Early Medical Intervention; Emergency Service, Hospital; Female; Guideline Adherence; Hospital Mortality; Hospitalization; Humans; Male; Medical Overuse; Meropenem; Middle Aged; Patient Care Bundles; Piperacillin, Tazobactam Drug Combination; Reimbursement Mechanisms; Retrospective Studies; Sepsis; Shock, Septic; Soft Tissue Infections; Time-to-Treatment; United States; Urinary Tract Infections; Vancomycin

Beta-lactam anti-infective levels after standard dosing have been shown to be subtherapeutic when renal clearance is augmented.. To determine if piperacillin and meropenem are found to be in their therapeutic range in infected critically ill patients when administered by continuous intravenous infusion (CII) assisted by a therapeutic drug monitoring (TDM) report issued by the pharmacy service.. This prospective non-controlled intervention study evaluated septic patients in an intensive care unit. Patients received a loading dose of meropenem or piperacillin-tazobactam and the antibiotics were afterwards administered by CII. Blood concentrations were determined by high-performance liquid chromatography assays. The adequacy of β-lactam therapy in the cohort subjected to intervention was assessed by determining whether plasma levels during CII were >4 times the informed minimum inhibitory concentration during the first 96 hours of treatment.. A total of 124 patients were subject to TDM during antibiotic treatment but, for the analysis of the fulfilment of pharmacodynamic requirements, data from 31/124 (25%) were excluded. Of the whole cohort of treatment courses, 57/93 (61.3%) reached the target level. Plasma levels were adequate in 41/70 (58.6%) and 16/23 (69.6%) of the patients treated with piperacillin-tazobactam and meropenem, respectively. Globally, recommendations based on TDM results were followed in 35/93 (37.6%) of the treatment courses.. The results of the study show that, in critically ill patients with sepsis, there is a significant proportion of treatment courses where target levels are not reached even if the antibiotics are administered by CII and TDM support is provided by the pharmacy service. This TDM support should be offered on a real-time basis to be really useful.

Topics: Aged; Anti-Bacterial Agents; Cohort Studies; Critical Illness; Drug Monitoring; Female; Humans; Infusions, Intravenous; Male; Meropenem; Middle Aged; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Sepsis

We describe a rare case of bloodstream infection and disseminated septic arthritis in a relatively fit and well 73-year-old retired farmer and gamekeeper, due to the zoonotic organism

Topics: Aged; Animals; Anti-Bacterial Agents; Arthritis, Infectious; Bacterial Zoonoses; Cattle; Decompression, Surgical; Discitis; Humans; Male; Piperacillin, Tazobactam Drug Combination; Rehabilitation; Sepsis; Streptococcal Infections; Streptococcus equi; Therapeutic Irrigation; Treatment Outcome

Survival Sepsis Campaign (SSC) guidelines have recommended broad-spectrum antibiotics prescriptions to cover the possible pathogenic microorganisms. However, mortality from sepsis is still high, as about one quarter of cases are thought to result in death. We analyzed nationwide health claims data of universal health insurance systems in Japan. Our aim was to describe the antibiotics prescriptions and underlying conditions of Japanese sepsis patients. In addition, we analyzed the factors associated with 30-day mortality. A total of 1188 patients aged ≥15 years were entered, of which 80.1% were ≥65 years old. Broad-spectrum antibiotics were prescribed for 53.8%. Carbapenem, Piperacillin Tazobactam and Anti-pseudomonas Cephalosporin were prescribed for 30.8%, 13.0% and 12.2% of the patients, respectively. (Some patients were counted twice) The overall 30-day mortality rate was 21.3%. Risk factors associated with 30-day mortality were examined by Cox proportional hazards regression analysis. Age of ≥85 years, malignancy, chronic kidney disease (CKD), shock and respiratory failure were selected as risk factors, but broad-spectrum antibiotics was not included. Sepsis is mostly observed in those aged 65 years and over. The rates of broad-spectrum antibiotics were restricted, and antibiotics were also not necessarily prescribed on the basis of SSC guidelines. However, broad-spectrum antibiotics did not improve the treatment outcome. Aging and underlying conditions like malignancy, CKD, shock and respiratory failure were poor prognostic factors.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Carbapenems; Humans; Japan; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Sepsis

Optimisation of antibiotic therapy for extracorporeal membrane oxygenation (ECMO) patients remains a pharmacological challenge. The objective of this study was to observe the plasma concentrations of commonly used antibiotics in intensive care for patients treated with extracorporeal membrane oxygenation.. The PHARMECMO study was a pilot, prospective study, conducted in a cardiac surgery intensive care unit. Every adult patient under ECMO support, with known or suspected sepsis and receiving antibiotic therapy, was eligible for inclusion. Plasma concentrations of antibiotics were determined by a combination of liquid chromatography and mass spectrometry.. Forty-four eligible patients were enrolled for 68 inclusions on a twelve-month period. For the association piperacillin-tazobactam (n=19), 68.7% of CT50 and 93.7% of Cmin reached the pharmacokinetic goals defined (64 mg.L-1 for CT50 and 16 mg.L-1 for Cmin). For cefotaxime (n=12), the pharmacokinetic goals (4 mg.L-1 for CT50 and 1 mg.L-1 for Cmin) were achieved in 100% of the cases for CT50 and in 81.8% of the cases for Cmin. Regarding imipenem (n=10), the pharmacokinetic goals were 16 mg.L-1 for CT50 and 4 mg.L-1 for Cmin. Only one CT50 was above 16 mg.L-1. For Cmin, 60% of the doses did not reach the target concentration. In our 10 patients, only one patient was considered as reaching the pharmacokinetic goals. Finally, for amikacin (n=6), four Cmax (66.7%) were infra-therapeutics for a target between 60 and 80 mg.L-1.. These preliminary results suggest that therapeutic drug monitoring could optimise the achievement of pharmacokinetic objectives associated with an effective antibiotic therapy. For most patients, the recommended doses of imipenem and amikacin did not achieve the pK targets.

Topics: Aged; Amikacin; Anti-Bacterial Agents; Cefotaxime; Cilastatin, Imipenem Drug Combination; Coronary Care Units; Drug Monitoring; Extracorporeal Membrane Oxygenation; Female; Gentamicins; Humans; Male; Middle Aged; Pilot Projects; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Sepsis; Tobramycin

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

Gram-negative organisms (GNOs) have increasing resistance rates to levofloxacin at Virginia Commonwealth University Health System (VCUHS), where levofloxacin is the most common agent added to provide double coverage of gram-negative infections. The goal of this study was to determine the adequacy of empiric gram-negative coverage for septic patients at our institution.. A retrospective review of patients admitted to VCUHS, from January 1, 2014, to December 31, 2014, with a diagnosis of sepsis, severe sepsis, or septic shock and documented infection, was performed to determine the adequacy of various empiric antibiotic combinations.. Of 219 patients who met the inclusion criteria, 56% of patients received monotherapy and 21% of patients received combination therapy (2 antibiotics) covering GNOs. GNOs (84%) were susceptible to piperacillin-tazobactam. When used in combination with cefepime and meropenem, levofloxacin did not increase coverage. However, levofloxacin provided an 8% increase in coverage and gentamicin provided an additional 13% increase in coverage, respectively, when used in combination with piperacillin-tazobactam.. Among septic patients at VCUHS, gentamicin provided increased gram-negative coverage when compared with levofloxacin. Although susceptibility to piperacillin-tazobactam alone was relatively low, the combination of piperacillin-tazobactam and gentamicin provided nearly equivalent coverage to meropenem and gentamicin.

Topics: Academic Medical Centers; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Cefepime; Cephalosporins; Female; Gram-Negative Bacteria; Humans; Levofloxacin; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Sepsis; Shock, Septic; Virginia; Young Adult

Results of a study of rates of acute kidney injury (AKI) in pediatric patients treated with vancomycin plus piperacillin-tazobactam or vancomycin plus alternative antipseudomonal β-lactams (APBLs) are reported.. A retrospective, single-center cohort study was performed. Pediatric patients were included in the study cohort if they received combination therapy for at least 48 hours, had documented baseline and follow-up serum creatinine levels, and had a documented serum vancomycin trough concentration. The primary outcome was the frequency of AKI, defined as a 50% or greater increase in serum creatinine concentration from baseline or an increase of at least 0.5 mg/dL from baseline. The secondary outcome was time to AKI onset.. A total of 474 patients were included. Among 100 patients who received vancomycin plus piperacillin-tazobactam, the rate of AKI was higher than the rate in the group treated with vancomycin plus alternative APBLs (27% versus 7%, p < 0.0001). The median time to AKI onset was shorter in the piperacillin-tazobactam group versus the alternative APBL group (3.8 versus 7.9 days, p = 0.0065). Patients who were administered piperacillin-tazobactam were almost 6 times as likely to develop AKI (odds ratio [OR], 5.955; 95% confidence interval [CI], 2.774-12.784), and patients who had a maximum vancomycin trough concentration greater than 20 mg/L were 7.5 times as likely to develop AKI (OR, 7.552; 95% CI, 3.625-15.734).. Pediatric patients treated with concomitant vancomycin and piperacillin-tazobactam had a higher rate of AKI, with faster AKI onset, than those who received vancomycin in combination with other APBLs.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Child; Creatinine; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Male; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Sepsis; Time Factors; Vancomycin

To determine the frequency and cause of inadequate initial antibiotic therapy with vancomycin and piperacillin-tazobactam in patients with severe sepsis and septic shock in the emergency department (ED), characterize its impact on patient outcomes, and identify patients who would benefit from an alternative initial empiric regimen.. Retrospective cohort study conducted between 2012 and 2015 in which 342 patients with culture-positive severe sepsis or septic shock who received initial vancomycin and piperacillin-tazobactam were reviewed to determine appropriateness of antimicrobial therapy, risk factors for inappropriate use, and outcome data. Univariate and multivariate regression analyses were determined to identify associations between inappropriate antibiotic use and outcomes and to identify risk factors that may predict which patients would benefit from an alternative initial regimen.. Vancomycin and piperacillin-tazobactam were inappropriate for 24% of patients with severe sepsis or septic shock, largely due to non-susceptible infections, particularly ESBL organisms and Clostridium difficile. Risk factors included multiple sources of infection (OR 4.383), admission from a skilled nursing facility (OR 3.763), a history of chronic obstructive pulmonary disease (COPD) (OR 3.175), intra-abdominal infection (OR 2.890), and immunosuppression (OR 1.930). We did not find a mortality impact.. Vancomycin and piperacillin-tazobactam were an inappropriate antibiotic combination for approximately 24% of patients with either severe sepsis or septic shock in the ED. Patients with known COPD, residence at a skilled nursing facility, a history concerning for Clostridium difficile, and immunosuppression would benefit from an alternative regimen. Future prospective studies are needed to validate these findings.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; California; Drug Therapy, Combination; Emergency Service, Hospital; Female; Hospital Mortality; Humans; Inappropriate Prescribing; Male; Middle Aged; Multivariate Analysis; Piperacillin, Tazobactam Drug Combination; Regression Analysis; Retrospective Studies; Sepsis; Shock, Septic; Vancomycin

In older adults, few studies confirm that adequate concentrations of antibiotics are achieved using current dosage regimens of intravenous β-lactam antibiotics. Our objective was to investigate trough concentrations of cefotaxime, meropenem, and piperacillin in older adults hospitalized with infection. We included 102 patients above 70 years of age. Total trough antibiotic concentrations were measured and related to suggested target intervals. Information on antibiotic dose, patient characteristics, and 28-day outcomes were collected from medical records and regression models were fitted. Trough concentrations for all three antibiotics exhibited considerable variation. Mean total trough concentrations for cefotaxime, meropenem, and piperacillin were 6.5 mg/L (range 0-44), 3.4 mg/L (range 0-11), and 30.2 mg/L (range 1.2-131), respectively. When a target range of non-species-related breakpoint - 5× non-species-related breakpoint was applied, only 36% of patients had both values within the target range. Regression models revealed that severe sepsis was associated with varying concentration levels and increasing age and diminishing kidney function with high concentration levels. The study was not powered to demonstrate consequences in clinical outcomes. Conclusively, in older adults treated with cefotaxime, meropenem, or piperacillin-tazobactam, trough antibiotic concentrations varied considerably. Better predictors to guide dosing regimens of β-lactam antibiotics or increased use of therapeutic drug monitoring are potential ways to address such variations.

Topics: Aged; Aged, 80 and over; Analysis of Variance; Bacterial Infections; beta-Lactams; Cefotaxime; Drug Monitoring; Female; Humans; Length of Stay; Male; Meropenem; Patient Readmission; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Sepsis; Sweden; Thienamycins

Sepsis is a common diagnosis in critical care with inpatient mortality rates up to 50%. Sepsis care is organized around source control, antibiotics, and supportive care. Drug disposition is deranged by changes in volume of distribution and regional blood flow, as well as multiple organ failure. Thus, assuring that each patient with sepsis attains pharmacokinetic targets is challenging. There is currently no commercially available FDA-approved assay to measure piperacillin-tazobactam, very commonly used as a beta-lactam/beta-lactamase inhibitor combination antibiotic in the intensive care unit (ICU).. Samples were prepared by ultrafiltration of plasma collected in lithium heparin Vacutainers. Separation was achieved by gradient elution on a C-18 column followed by UV detection at 214 nm. The method is validated in residual blood samples allowing investigators to exploit a waste product to develop insight into beta-lactam pharmacokinetics in the ICU.. Accuracy and precision were within the 25% CLIA error standard for other antibiotic assays. Free piperacillin concentrations were also in good agreement with total piperacillin concentrations measured in the same plasma by an assay in clinical use outside the United States.. We describe a method for measuring piperacillin and tazobactam that meets clinical validation standards. Quick turnaround time and excellent accuracy on a low-cost platform make this method more than adequate for use as a routine therapeutic drug monitoring tool.

Topics: Blood Specimen Collection; Chromatography, High Pressure Liquid; Chromatography, Reverse-Phase; Drug Monitoring; Humans; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sepsis; Tazobactam

The objective of this study was to evaluate AKI incidence with concomitant vancomycin and piperacillin/tazobactam (PTZ) compared to vancomycin and cefepime (FEP) in critically ill patients.. A retrospective, cohort study was conducted in adult critically ill patients from January 1, 2014 to December 31, 2017. The primary aim was to compare the incidence of AKI during concomitant therapy or until hospital discharge. Secondary analyses included AKI severity, time to AKI as well as recovery, and clinical outcomes.. Overall, 333 patients were evaluated. The AKI rate in the vancomycin/PTZ group and vancomycin/FEP group were similar (19.5% vs. 17.3%, respectively, p = .612). Renal replacement therapy (RRT) was initiated in 10.0% and 3.8% administered vancomycin/PTZ and vancomycin/FEP groups, respectively (p = .04). Multivariate regression found vancomycin/PTZ was not associated with an increased risk of developing AKI although the presence of shock was identified as an independent risk factor (odds ratio, 3.22; 95% CI, 1.66-6.26). No significant differences in hospital or ICU length of stay or in-hospital mortality were observed between study groups.. Concomitant PTZ and vancomycin in ICU patients was not associated with an increased risk of developing AKI compared to FEP and vancomycin combinations. More patients administered vancomycin/PTZ received RRT.

Topics: Acute Kidney Injury; Adult; Aged; Anti-Bacterial Agents; Cefepime; Critical Illness; Female; Humans; Incidence; Male; Middle Aged; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Sepsis

Myiasis; is defined as the infestation of dead or living tissues of humans and animals by the diptera larvae. It is prevalent all over the world, especially in tropical and subtropical countries with low socioeconomic status. Myiasis of humans has been associated with low socioeconomic status, alcoholism, mental or neurological diseases, poor personal hygiene, patients with varicose veins, diabetes, malnutrition, advanced stage cancer, pediculosis, immunosuppression, sexually transmitted disease, gingivitis and other oral cavity lesions. Myiasis is most commonly seen as skin invasion in the human body, but can be observed in many areas such as eye, ear, nose, throat, urogenital, intestinal, cerebral and tracheopulmonary. Tracheo pulmonary myiasis is a very rare condition. This report presents a case of pneumonia-associated sepsis in a patient with a tracheostomy accompanied by third-stage larval Sarcophagidae. A 51-year-old male patient developed hypoxic brain injury after myocardial infarction 10 months ago before his admission to the hospital. Tracheostomy and percutaneous endoscopic gastrostomy were performed. Shortness of breath and fever were present for five days. The patient has been admitted to the emergency service with the reason for the deterioration of the general situation. The patient was unconscious. Purulent secretion in the tracheostomy area and bilateral crepitation rales in the lung bases were detected. Leukocyte level was normal with C reactive protein (CRP) 14 mg/dl. Nodular infiltration was detected bilaterally in the middle and lower zones, more prominently in the right thoracic computerized tomography. Seftriaxon, moxifloxacin and fluid therapy were initiated in the patient who was admitted with pneumonia-related sepsis diagnosis. The tracheostomy cannula has changed. On the fourth day of admission, Sarcophagidae third stage larvae were detected in deep tracheal aspiration. Treatment of piperacillin/tazobactam and teicoplanin was started by discontinuing the current antibiotherapy of the patient who had no clinical response and elevated CRP level, 18 mg/dl. The patient was discharged on the 25th day of hospitalization with improved clinical and laboratory responses. Complete healing was observed in the control performed by the home care unit. Bed-dependent, lack of self-care, and poor tracheostomy hygiene were risk factors for this patient. In this case, fluid therapy and antibiotic treatment for sepsis was given but no treatment f

Topics: Animals; Humans; Hypoxia, Brain; Larva; Lung Diseases; Male; Middle Aged; Myiasis; Piperacillin, Tazobactam Drug Combination; Pneumonia; Sarcophagidae; Sepsis; Teicoplanin; Tracheostomy; Treatment Outcome

Topics: Abdominal Pain; Anti-Bacterial Agents; Bacteremia; Ceftriaxone; Fusobacterium Infections; Fusobacterium necrophorum; Humans; Liver Abscess; Male; Metronidazole; Middle Aged; Nausea; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sepsis; Treatment Outcome; Vomiting

Guidelines for the treatment of sepsis, febrile neutropenia, and hospital-acquired pneumonia caused by

Topics: Anti-Bacterial Agents; Cefepime; Ceftazidime; Cephalosporins; Ciprofloxacin; Drug Combinations; Drug Resistance, Multiple, Bacterial; Febrile Neutropenia; Humans; Iatrogenic Disease; Meropenem; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia; Practice Guidelines as Topic; Pseudomonas aeruginosa; Pseudomonas Infections; Sepsis; Tazobactam; Thienamycins; Tobramycin

Early administration of appropriate empiric antibiotics is essential for achieving the best possible outcomes in sepsis. Yet the choice of antibiotic therapy has become more challenging due to recent reports of nephrotoxicity with the combination of vancomycin and piperacillin/tazobactam, the "workhorse" regimen at many institutions. In this article we assess the evidence for nephrotoxicity and its possible mechanisms, provide recommendations for risk mitigation, address the advantages and disadvantages of alternative antibiotic choices, and suggest areas for future research.

Topics: Anti-Bacterial Agents; Combined Modality Therapy; Drug Therapy, Combination; Humans; Kidney; Kidney Diseases; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sepsis; Vancomycin

To determine if time to initial antimicrobial is associated with progression of severe sepsis to septic shock.. Retrospective cohort.. Six hundred fifty-six bed urban academic medical center.. Emergency department patients greater than or equal to 18 years old with severe sepsis and/or septic shock and antimicrobial administration within 24 hours. Patients with shock on presentation were excluded.. Not available.. We identified 3,929 severe sepsis patients, with overall mortality 12.8%. Nine hundred eighty-four patients (25.0%) progressed to septic shock. The median time to antimicrobial was 3.77 hours (interquartile range = 1.96-6.42) in those who progressed versus 2.76 hours (interquartile range = 1.60-4.82) in those who did not (p < 0.001). Multivariate logistic regression demonstrated that male sex (odds ratio = 1.18; 95% CI, 1.01-1.36), Charlson Comorbidity Index (odds ratio = 1.18; 95% CI, 1.11-1.27), number of infections (odds ratio = 1.05; 95% CI, 1.02-1.08), and time to first antimicrobial (odds ratio = 1.08; 95% CI, 1.06-1.10) were associated with progression. Each hour until initial antimicrobial administration was associated with a 8.0% increase in progression to septic shock. Additionally, time to broad-spectrum antimicrobial was associated with progression (odds ratio = 1.06; 95% CI, 1.05-1.08). Time to initial antimicrobial was also associated with in-hospital mortality (odds ratio = 1.05; 95% CI, 1.03-1.07).. This study emphasizes the importance of early, broad-spectrum antimicrobial administration in severe sepsis patients admitted through the emergency department, as longer time to initial antimicrobial administration is associated with increased progression of severe sepsis to septic shock and increased mortality.

Topics: Adult; Aged; Anti-Bacterial Agents; Ceftriaxone; Comorbidity; Disease Progression; Female; Hospital Mortality; Humans; Length of Stay; Levofloxacin; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Sepsis; Sex Factors; Shock, Septic; Time Factors; Time-to-Treatment; Vasoconstrictor Agents

The pharmacokinetics of β-lactam antibiotics have not been well defined in critically ill patients with cirrhosis.. We reviewed data from critically ill patients with cirrhosis and matched controls in whom routine therapeutic drug monitoring of two broad-spectrum β-lactam antibiotics (piperacillin/tazobactam and meropenem) had been performed. Serum drug concentrations were measured twice by high-performance liquid chromatography. Antibiotic pharmacokinetics were calculated using a one-compartment model. We considered that therapy was adequate when serum drug concentrations were between 4 and 8 times the minimal inhibitory concentration of Pseudomonas aeruginosa during optimal periods of time for each drug (≥ 50% for piperacillin/tazobactam; ≥ 40% for meropenem).. We studied 38 patients with cirrhosis (16 for piperacillin/tazobactam and 22 for meropenem) and 38 matched controls. Drug dosing was similar in the two groups. The pharmacokinetics analysis showed a lower volume of distribution of meropenem (P = 0.05) and a lower antibiotic clearance of piperacillin/tazobactam (P = 0.009) in patients with cirrhosis than in the matched controls. Patients with cirrhosis were more likely than those without cirrhosis to have excessive serum β-lactam concentrations (P = 0.015), in particular for piperacillin/tazobactam.. Standard β-lactam antibiotics regimens resulted in excessive serum concentrations in two thirds of the patients with cirrhosis. This was particularly true for piperacillin/tazobactam, probably because of reduced drug clearance.

Topics: Aged; Anti-Bacterial Agents; Belgium; Case-Control Studies; Chromatography, High Pressure Liquid; Critical Illness; Databases, Factual; Drug Monitoring; Female; Humans; Liver Cirrhosis; Logistic Models; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Multivariate Analysis; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sepsis; Thienamycins

Topics: Acetone; Acidosis; Adult; Anti-Bacterial Agents; Blood Glucose; Confusion; Diabetes Complications; Fever; Fluid Therapy; Humans; Leg Injuries; Male; Methicillin-Resistant Staphylococcus aureus; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sepsis; Sodium Bicarbonate; Staphylococcal Infections; Vancomycin

Expanding antimicrobial resistance patterns in the face of stagnant growth in novel antibiotic production underscores the importance of antibiotic stewardship in which de-escalation remains an integral component. We measured the frequency of antibiotic de-escalation in a tertiary care medical center with an established antimicrobial stewardship program to provide a plausible benchmark for de-escalation.. A retrospective, observational study was performed by review of randomly selected electronic medical records of 240 patients who received simultaneous piperacillin/tazobactam and vancomycin from January to December 2011 at an 885-bed tertiary care medical center. Patient characteristics including antibiotic regimen, duration and indication, culture results, length of stay, and hospital mortality were evaluated. Antibiotic de-escalation was defined as the use of narrower spectrum antibiotics or the discontinuation of antibiotics after initiation of piperacillin/tazobactam and vancomycin therapy. Subjects dying within 72 h of antibiotic initiation were considered not de-escalated for subsequent analysis and were subtracted from the study population in determining a modified mortality rate.. The most commonly documented indications for piperacillin/tazobactam and vancomycin therapy were pneumonia and sepsis. Of the 240 patients studied, 151 (63%) had their antibiotic regimens de-escalated by 72 h. The proportion of patients de-escalated by 96 h with positive vs. negative cultures was similar, 71 and 72%, respectively. Median length of stay was 4 days shorter in de-escalated patients, and the difference in adjusted mortality was not significant (p = 0.82).. The empiric antibiotic regimens of approximately two-thirds of patients were de-escalated by 72 h in an institution with a well-established antimicrobial stewardship program. While this study provides one plausible benchmark for antibiotic de-escalation, further studies, including evaluations of antibiotic appropriateness and patient outcomes, are needed to inform decisions on potential benchmarks for antibiotic de-escalation.

Topics: Acute Disease; Aged; Anti-Bacterial Agents; Drug Resistance, Bacterial; Drug Therapy, Combination; Female; Hospital Mortality; Humans; Length of Stay; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia; Retrospective Studies; Sepsis; Vancomycin

Tungiasis is one of the neglected tropical diseases; it affects up to 40% of individuals living in societies with poor housing and sanitation standards. In endemic areas, Tunga infestation, which predominantly affects the periungual areas of the lower limbs in humans, is associated with considerable morbidity and poor quality of life.. A 78-year-old woman of African descent presented with pain, inflammation, suppuration, ulceration, and deformation of digits of all four limbs. She had a total of 1146 embedded sand fleas: 812 in lower limbs and 334 in her hands. She was febrile; her full blood count revealed pancytopenia and blood cultures were positive for Staphylococcus aureus and Streptococcus pyogenes isolates. Furthermore, she had severe hyponatremia. We applied 20% salicylated petroleum jelly followed by the manual removal of embedded sand fleas with a sterile needle. Intravenously administered piperacillin-tazobactam, topical ivermectin, ferrous sulfate, folic acid, tolvaptan, albendazole, multivitamins, and tetanus prophylaxis were instituted. She was discharged home after 16 days of hospitalization.. Tungiasis is a neglected disease of concern in underprivileged societies that is preventable and curable. Early recognition and prompt treatment is crucial to prevent complications in this disease which may potentially mimic other conditions resulting in erroneous management.

Topics: Aged; Animals; Anti-Bacterial Agents; Antidiuretic Hormone Receptor Antagonists; Benzazepines; Ectoparasitic Infestations; Extremities; Female; Ferrous Compounds; Folic Acid; Humans; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Poverty Areas; Quality of Life; Sepsis; Severity of Illness Index; Tanzania; Tetanus Toxoid; Tolvaptan; Treatment Outcome; Tunga; Tungiasis; Vitamins

Topics: Amikacin; Anti-Bacterial Agents; Brain Abscess; Drainage; Frontal Lobe; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Long Term Adverse Effects; Magnetic Resonance Imaging; Male; Neurosurgical Procedures; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sepsis; Serratia marcescens; Tomography, X-Ray Computed; Treatment Outcome

Most adult patients receiving extracorporeal membrane oxygenation (ECMO) require antibiotic therapy, however the pharmacokinetics of β-lactams have not been well studied in these conditions. In this study, data from all patients receiving ECMO support and meropenem (MEM) or piperacillin/tazobactam (TZP) were reviewed. Drug concentrations were measured 2h after the start of a 30-min infusion and just before the subsequent dose. Therapeutic drug monitoring (TDM) results in ECMO patients were matched with those in non-ECMO patients for (i) drug regimen, (ii) renal function, (iii) total body weight, (iv) severity of organ dysfunction and (v) age. Drug concentrations were considered adequate if they remained 4-8× the clinical MIC breakpoint for Pseudomonas aeruginosa for 50% (TZP) or 40% (MEM) of the dosing interval. A total of 41 TDM results (27 MEM; 14 TZP) were obtained in 26 ECMO patients, with 41 matched controls. There were no significant differences in serum concentrations or pharmacokinetic parameters between ECMO and non-ECMO patients, including Vd [0.38 (0.27-0.68) vs. 0.46 (0.33-0.79)L/kg; P=0.37], half-life [2.6 (1.8-4.4) vs. 2.9 (1.7-3.7)h; P=0.96] and clearance [132 (66-200) vs. 141 (93-197)mL/min; P=0.52]. The proportion of insufficient (13/41 vs. 12/41), adequate (15/41 vs. 19/41) and excessive (13/41 vs. 10/41) drug concentrations was similar in ECMO and non-ECMO patients. Achievement of target concentrations of these β-lactams was poor in ECMO and non-ECMO patients. The influence of ECMO on MEM and TZP pharmacokinetics does not appear to be significant.

Topics: Adult; Anti-Bacterial Agents; beta-Lactams; Case-Control Studies; Extracorporeal Membrane Oxygenation; Female; Humans; Male; Meropenem; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pseudomonas Infections; Sepsis; Serum; Thienamycins; Treatment Outcome

The present study is a non-inferiority study based on a descriptive and comparative case series for comparison of generic vs. original intravenous antimicrobials in septic oncology patients at an oncology private ICU. 1906 cancer patients admitted to Arturo Lopez Perez Foundation, Chile, were included in this study. After recruitment, a first retrospective group of 206 septic cancer patients recorded from 1st January, 2008 until July 14th, 2010, treated with original antibiotics (cefoperazone-sulbactam, imipenem-cilastatin, piperacillin-tazobactam) were included for analyses and a second prospective group of 143 septic cancer patients recorded from July 15th, 2010 until January 02, 2013, treated with the same but generic antibiotics were also included for comparisons. The trial protocol was developed in accordance with Helsinki and Good Clinical Practices recommendations. The results of this study showed no significant differences between the 2 groups in days of treatment, rate of success and lab test determinations (white cell count, PCR and procalcitonin), with lower, but not significant, total bed days and CPU bed days for generic antibiotics. Therefore, we conclude that the safety and efficacy of the generic antibiotics cefactam®, imipen® and Piperazam® are not inferior to original antibiotics for the treatment of severe sepsis in hospitalised patients at the Arturo Lopez Perez Foundation.

Topics: Administration, Intravenous; Anti-Bacterial Agents; Cefoperazone; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drugs, Generic; Female; Humans; Imipenem; Male; Middle Aged; Oncology Service, Hospital; Penicillanic Acid; Pilot Projects; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Retrospective Studies; Sepsis; Sulbactam; Treatment Outcome

Piperacillin-tazobactam (PTZ) is frequently used as empirical and targeted therapy for Gram-negative sepsis. Time-dependent killing properties of PTZ support the use of extended-infusion (EI) dosing; however, studies have shown inconsistent benefits of EI PTZ treatment on clinical outcomes. We performed a retrospective cohort study of adult patients who received EI PTZ treatment and historical controls who received standard-infusion (SI) PTZ treatment for presumed sepsis syndromes. Data on mortality rates, clinical outcomes, length of stay (LOS), and disease severity were obtained. A total of 843 patients (662 with EI treatment and 181 with SI treatment) were available for analysis. Baseline characteristics of the two groups were similar, except for fewer female patients receiving EI treatment. No significant differences between the EI and SI groups in inpatient mortality rates (10.9% versus 13.8%; P = 0.282), overall LOS (10 versus 12 days; P = 0.171), intensive care unit (ICU) LOS (7 versus 6 days; P = 0.061), or clinical failure rates (18.4% versus 19.9%; P = 0.756) were observed. However, the duration of PTZ therapy was shorter in the EI group (5 versus 6 days; P < 0.001). Among ICU patients, no significant differences in outcomes between the EI and SI groups were observed. Patients with urinary or intra-abdominal infections had lower mortality and clinical failure rates when receiving EI PTZ treatment. We did not observe significant differences in inpatient mortality rates, overall LOS, ICU LOS, or clinical failure rates between patients receiving EI PTZ treatment and patients receiving SI PTZ treatment. Patients receiving EI PTZ treatment had a shorter duration of PTZ therapy than did patients receiving SI treatment, and EI dosing may provide cost savings to hospitals.

Topics: Aged; Anti-Bacterial Agents; Cost-Benefit Analysis; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Infusions, Intravenous; Length of Stay; Male; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Sepsis; Survival Analysis; Syndrome; Tertiary Healthcare

Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiological entity, associated with a vast array of medical conditions and a variety of presenting symptoms. There is a characteristic pattern of radiographic features alongside suggestive clinical manifestations, which lead to a diagnosis of PRES. This report describes the case of a 39 years old, previously normotensive woman, who presented on day 7 postpartum with generalised tonic clonic seizures, reduced conscious level and a history of blurred vision and headache. She was treated immediately as eclamptic and transferred to the intensive care unit for stabilisation. Following an inconclusive CT result, an MRI was performed 2 days after presentation, which demonstrated white matter changes consistent with those found in PRES. She made a full recovery and a repeat MRI scan 7 weeks later showed no progression of the lesions noted on the original scan.

Topics: Adult; Anti-Bacterial Agents; Antihypertensive Agents; Critical Care; Diagnosis, Differential; Female; Fluid Therapy; Follow-Up Studies; Headache; Humans; Labetalol; Magnesium Sulfate; Magnetic Resonance Imaging; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Posterior Leukoencephalopathy Syndrome; Postpartum Period; Seizures; Sepsis; Tomography, X-Ray Computed; Treatment Outcome

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

Sepsis is a potentially life-threatening condition that requires urgent management in an Emergency Department (ED). Evidence-based guidelines for managing sepsis have been developed; however, their integration into routine practice is often incomplete. Care maps may help clinicians meet guideline targets more often.. To determine if electronic clinical practice guidelines (eCPGs) improve management of patients with severe sepsis and septic shock (SS/SS).. The impact of an eCPG on the management of patients presenting with SS/SS over a 3-year period at a tertiary care ED was evaluated using retrospective case-control design and chart review methods. Cases and controls, matched by age and sex, were chosen from an electronic database using physician sepsis diagnoses. Data were compared using McNemar tests or paired t-tests, as appropriate.. Overall, 51 cases and controls were evaluated; the average age was 62 years, and 60% were male. eCPG patients were more likely to have a central venous pressure and central venous oxygen saturation measured; however, lactate measurement, blood cultures, and other investigations were similarly ordered (all p > 0.05). The administration of antibiotics within 3 h (63% vs. 41%; p = 0.03) and vasopressors (45% vs. 20%; p = 0.02) was more common in the eCPG group; however, use of corticosteroids and other interventions did not differ between the groups. Overall, survival was high and similar between groups.. A sepsis eCPG experienced variable use; however, physicians using the eCPG achieved more quality-of-care targets for SS/SS. Strategies to increase the utilization of eCPGs in Emergency Medicine seem warranted.

Topics: Aged; Anti-Bacterial Agents; Clinical Protocols; Disease Management; Emergency Service, Hospital; Female; Hospitals, Teaching; Humans; Internet; Male; Middle Aged; Penicillanic Acid; Pilot Projects; Piperacillin; Piperacillin, Tazobactam Drug Combination; Practice Guidelines as Topic; Sepsis; Shock, Septic; Treatment Outcome

Severe sepsis and septic shock can alter the pharmacokinetics of broad-spectrum β-lactams (meropenem, ceftazidime/cefepime, and piperacillin-tazobactam), resulting in inappropriate serum concentrations. Obesity may further modify the pharmacokinetics of these agents. We reviewed our data on critically ill obese patients (body mass index of ≥ 30 kg/m(2)) treated with a broad-spectrum β-lactam in whom therapeutic drug monitoring was performed and compared the data to those obtained in critically nonobese patients (body mass index of <25 kg/m(2)) to assess whether there were differences in reaching optimal drug concentrations for the treatment of nosocomial infections. Sixty-eight serum levels were obtained from 49 obese patients. There was considerable variability in β-lactam serum concentrations (coefficient of variation of 50% to 92% for the three drugs). Standard drug regimens of β-lactams resulted in insufficient serum concentrations in 32% of the patients and overdosed concentrations in 25%. Continuous renal replacement therapy was identified by multivariable analysis as a risk factor for overdosage and a protective factor for insufficient β-lactam serum concentrations. The serum drug levels from the obese cohort were well matched for age, gender, renal function, and sequential organ failure assessment (SOFA) score to 68 serum levels measured in 59 nonobese patients. The only difference observed between the two cohorts was in the subgroup of patients treated with meropenem and who were not receiving continuous renal replacement therapy: serum concentrations were lower in the obese cohort. No differences were observed in pharmacokinetic variables between the two groups. Routine therapeutic drug monitoring of β-lactams should be continued in obese critically ill patients.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; beta-Lactams; Case-Control Studies; Cefepime; Ceftazidime; Cephalosporins; Drug Monitoring; Enzyme Inhibitors; Female; Humans; Male; Meropenem; Middle Aged; Obesity; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Renal Replacement Therapy; Sepsis; Shock, Septic; Tazobactam; Thienamycins; Young Adult

We changed from ampicillin and gentamicin (AG) to piperacillin-tazobactam (PT) for routine treatment of suspected early-onset sepsis. The rationale for this change included ototoxic and renal toxic effects of gentamicin, resistance to gentamicin in late-onset infections and emergence of ampicillin resistant Escherichia coli. A before and after study was designed before the start of PT administration to monitor whether PT was associated with altered outcomes within the 501 to 1500 g birth weight (Very Low Birth Weight) population.. Both unmatched and matched comparisons of AG (2007 to 2009) and PT (2010 to 2011) exposed infants are reported. Cohorts were evaluated for initial effectiveness for congenital infections, subsequent morbidities and mortality.. Data from 714 patients were collected (499 AG and 215 PT in the unmatched and 301 AG and 183 PT in the matched cohorts). No significant differences in demographics or initial Apgar scores were noted in the unmatched or matched comparisons. There were significant differences in many of the outcomes of interest in both the matched and unmatched comparisons including less necrotizing enterocolitis (NEC) and less diaper rash with PT versus AG. The only adverse finding with PT was a small, but statistically significant elevation in alkaline phosphatase.. Use of PT as the initial empiric antibiotic for very low birth weight infants was not associated with adverse microbiological outcomes. There was no increase in major morbidities. Although outcomes were superior in ≤ 1500 g infants treated with PT when compared with AG, the study design does not allow us to conclude that others will see a reduction in NEC or diaper rash if they implement this alternative.

Topics: Alkaline Phosphatase; Ampicillin; Apgar Score; Diaper Rash; Female; Gentamicins; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Male; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Sepsis; Treatment Outcome

A 48-year-old lady who presented with sepsis secondary to a pelvi-ureteric junction obstruction was treated with an extended course of piperacillin/tazobactam. Four days after completing the course she developed thrombocytopaenia. Intravenous immunoglobulin was required to bring her platelet count back to normal. In the absence of other causes the authors believe that a delayed reaction to piperacillin/tazobactam was the cause of her thrombocytopaenia.

Topics: Anti-Bacterial Agents; Diagnosis, Differential; Female; Follow-Up Studies; Humans; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Platelet Count; Sepsis; Thrombocytopenia; Time Factors

A 10-year-old boy with acquired, very severe aplastic anemia developed acute lung injury after the administration of equine antithymocyte globulin, during conditioning for allogenic bone marrow transplantation. Limited cases of antithymocyte globulin-induced acute lung injury have been described in adults. The respiratory worsening was sudden and required mechanical ventilation. The clinical course was complicated by sepsis with Escherichia coli, vancomycin-resistant enterococci, and Stenotrophomonas maltophilia. Implications for treatment are discussed and earlier literature is reviewed.

Topics: Acute Lung Injury; Anemia, Aplastic; Animals; Anti-Bacterial Agents; Antilymphocyte Serum; Bacterial Infections; Bone Marrow Transplantation; Child; Cyclophosphamide; Horses; Humans; Male; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sepsis; Transplantation Conditioning; Vancomycin; Vidarabine

This study assessed the epidemiology and antimicrobial resistance of pathogens associated with bloodstream infections in Canadian hospitals between 2007 and 2009. Tertiary-care medical centers representing 8 of 10 Canadian provinces submitted bloodstream infection pathogens from patients attending hospital clinics, emergency rooms, medical/surgical wards, and intensive care units. Over 8,000 blood culture pathogens were collected. The 10 most common pathogens (representing 80.9% of all isolates) were Escherichia coli (1856 [22.6%]), Staphylococcus aureus (1457 [17.7%] including 1101 methicillin-susceptible Staphylococcus aureus and 356 methicillin-resistant Staphylococcus aureus), coagulase-negative staphylococci (907 [11.0%]), Klebsiella pneumoniae (600 [7.3%]), Streptococcus pneumoniae (470 [5.7%]), Enterococcus faecalis (360 [4.4%]), Pseudomonas aeruginosa (333 [4.0%]), viridans group streptococci (321 [3.9%]), Enterobacter cloacae (193 [2.3%]), and Streptococcus pyogenes (159 [1.9%]). The most active agents against Gram-negative bacilli were carbapenems (e.g., meropenem and ertapenem) and piperacillin-tazobactam, while for Gram-positive cocci, they were vancomycin, linezolid, and daptomycin.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Infective Agents; Blood; Canada; Candida; Carbapenems; Child; Child, Preschool; Drug Resistance, Bacterial; Drug Resistance, Fungal; Emergency Service, Hospital; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Infant; Infant, Newborn; Intensive Care Units; Microbial Sensitivity Tests; Middle Aged; Outpatient Clinics, Hospital; Patients' Rooms; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Polymerase Chain Reaction; Prevalence; Sepsis

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

In this study, an appropriate sepsis model was created in rats. Additionally, the effects of steroid treatments on survival, in connection with antibiotic treatment, were investigated. The sepsis model performed via intraperitoneal injection of 3 ml/kg fecal suspension was determined as the most appropriate model for our study. Fifteen rats were used to investigate the effect of piperacillin-tazobactam on sepsis treatment. Forty-five randomly selected rats were used to investigate the efficacy of the antibiotic-plus-steroid combination. The rats were divided into three groups of 15 rats each. Twelve hours after the administration of fecal suspension, methylprednisolone (MP) at the dose of 0.25, 0.5, and 2 mg/kg/day was given to each group, respectively, in addition to an antibiotic administered intravenously. In order to investigate the effect of steroids alone in the treatment of sepsis, 0.5 mg/kg/day MP was given intravenously to 15 rats, 12 h after the fecal suspension was administered. It was concluded that administration of MP alone shortens survival time in rats with sepsis, whereas antibiotic therapy alone increases survival time significantly in rats with sepsis. It was seen that the antibiotic-plus-steroid treatment increases survival significantly compared to rats with no treatment (p < 0.05). In addition, steroids, when added to an antibiotic treatment in sepsis, affect survival positively when compared to the group with antibiotic therapy alone, depending on the dose given. Although, not statistically significant, high doses decrease survival (p > 0.05), and very low doses increase survival and mean survival time (p > 0.05) on the basis of clinical observation and average life time. However, low doses were found to increase survival significantly (p < 0.05). We concluded that low-dose MP, in addition to the appropriate antibiotic therapy, is the optimal in the treatment of rats with intraabdominal sepsis.

Topics: Animals; Disease Models, Animal; Methylprednisolone; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Rats; Rats, Sprague-Dawley; Sepsis

Topics: Anti-Bacterial Agents; Exanthema; Humans; Infant, Newborn; Infant, Premature; Male; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sepsis; Tazobactam

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

Piperacillin/tazobactam (P/T) has been used in NICU since 1999 as part of the empirical treatment for presumed sepsis. We studied the microbiological and clinical efficacy and safety of P/T use in newborns with sepsis, using a retrospective analysis of medical records of all newborns treated with P/T (in association with amikacin) during 1999-2003. P/T plus amikacin was used for 353 episodes of presumed sepsis occurring in 252 newborns: 105 episodes occurred in 100 newborns treated for 5-14 d while in 248 (70%) episodes the treatment was discontinued after 2-3 d. 123 pathogens were isolated from the blood cultures (40 in the 5-14 d group and 83 in those treated for 2-3 d only). There were 56 Gram-negative, 55 Gram-positive and 12 Candida spp. isolates. Klebsiella spp. (40%) and E. coli (30%) were the most commonly isolated Gram-negative pathogens; coagulase-negative Staphylococcus (CONS) represented 95% of the Gram-positive pathogens isolated. Pathogen eradication was achieved within 48-72 h of therapy in 93% Gram-negative organisms. There were no clinical, laboratory or cranial ultrasound adverse effects associated with P/T use. We conclude that P/T in association with amikacin is microbiologically and clinically efficacious and safe in the treatment of sepsis in newborns.

Topics: Amikacin; Anti-Bacterial Agents; Drug Resistance, Bacterial; Drug Therapy, Combination; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Infant, Newborn; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Sepsis

We report the first case of Lemierre's disease caused by a co-infection with A. haemolyticum and F. necrophorum. A characteristic skin rash and predominant growth on multiple blood cultures suggests a causative role for Arcanobacterium. Failures of penicillin therapy in A. haemolyticum infections should be considered when the initial antibiotic regimen is chosen.

Topics: Actinomycetales; Actinomycetales Infections; Adult; Anti-Bacterial Agents; Drug Therapy, Combination; Fusobacterium Infections; Humans; Jugular Veins; Male; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sepsis; Thrombophlebitis; Vancomycin