Piperacillin-tazobactam Treatment Research Articles

Comparative Impact of an Optimized PK/PD Target Attainment of Piperacillin-Tazobactam vs. Meropenem on the Trend over Time of SOFA Score and Inflammatory Biomarkers in Critically Ill Patients Receiving Continuous Infusion Monotherapy for Treating Documented Gram-Negative BSIs and/or VAP.

(1) Background: The advantage of using carbapenems over beta-lactam/beta-lactamase inhibitor combinations in critically ill septic patients still remains a debated issue. We aimed to assess the comparative impact of an optimized pharmacokinetic/pharmacodynamic (PK/PD) target attainment of piperacillin-tazobactam vs. meropenem on the trend over time of both Sequential Organ Failure Assessment (SOFA) score and inflammatory biomarkers in critically ill patients receiving continuous infusion (CI) monotherapy with piperacillin-tazobactam or meropenem for treating documented Gram-negative bloodstream infections (BSI) and/or ventilator-associated pneumonia (VAP). (2) Methods: We performed a retrospective observational study comparing critically ill patients receiving targeted treatment with CI meropenem monotherapy for documented Gram-negative BSIs or VAP with a historical cohort of critical patients receiving CI piperacillin-tazobactam monotherapy. Patients included in the two groups were admitted to the general and post-transplant intensive care unit in the period July 2021-September 2023 and fulfilled the same inclusion criteria. The delta values of the SOFA score between the baseline of meropenem or piperacillin-tazobactam treatment and those at 48-h (delta 48-h SOFA score) or at 7-days (delta 7-days SOFA) were selected as primary outcomes. Delta 48-h and 7-days C-reactive protein (CRP) and procalcitonin (PCT), microbiological eradication, resistance occurrence, clinical cure, multi-drug resistant colonization at 90-day, ICU, and 30-day mortality rate were selected as secondary outcomes. Univariate analysis comparing primary and secondary outcomes between critically ill patients receiving CI monotherapy with piperacillin-tazobactam vs. meropenem was carried out. (3) Results: Overall, 32 critically ill patients receiving CI meropenem monotherapy were compared with a historical cohort of 43 cases receiving CI piperacillin-tazobactam monotherapy. No significant differences in terms of demographics and clinical features emerged at baseline between the two groups. Optimal PK/PD target was attained in 83.7% and 100.0% of patients receiving piperacillin-tazobactam and meropenem, respectively. No significant differences were observed between groups in terms of median values of delta 48-h SOFA (0 points vs. 1 point; p = 0.89) and median delta 7-days SOFA (2 points vs. 1 point; p = 0.43). Similarly, no significant differences were found between patients receiving piperacillin-tazobactam vs. meropenem for any of the secondary outcomes. (4) Conclusion: Our findings may support the contention that in critically ill patients with documented Gram-negative BSIs and/or VAP, the decreases in the SOFA score and in the inflammatory biomarkers serum levels achievable with CI piperacillin-tazobactam monotherapy at 48-h and at 7-days may be of similar extent and as effective as to those achievable with CI meropenem monotherapy provided that optimization on real-time by means of a TDM-based expert clinical pharmacological advice program is granted.

Predictive Value of CRP, PCT and ESR on Piperacillin-Tazobactam in Treating Chronic Obstructive Pulmonary Disease with Pneumonia.

The goal of this paper was to investigate the predictive value on the efficacy of C-reactive protein (CRP), procalcitonin (PCT), and erythrocyte sedimentation rate (ESR) on piperacillin-tazobactam in the treatment of patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) complicated with pneumonia. From January 2018 to May 2021, 52 AECOPD patients (AECOPD group) and 91 AECOPD patients with pneumonia (pneumonia group) were enrolled, and the levels of CRP, PCT, and ESR were compared. The pneumonia group was divided into a mild group and a severe group, and the correlation between the levels of CRP, PCT, and ESR and the severity of pneumonia was analyzed. The patients in the pneumonia group were treated with piperacillin and tazobactam, and the clinical efficacy of CRP, PCT, and ESR levels was analyzed. The pneumonia group, particularly the severe subtype, had higher CRP, PCT, and ESR than the AECOPD group. CRP, PCT, and ESR levels were related to the severity of pneumonia and were negatively associated with the efficacy of piperacillin and tazobactam. The AUC of the combined detection of CRP, PCT, and ESR levels was greater than 0.8 to evaluate the efficacy of piperacillin-tazobactam treatment. CRP ≥ 67.19 mg/L, PCT ≥ 1.73 ng/mL, and ESR ≥ 29.42 mm/hour were the related factors affecting the efficacy of piperacillin-tazobactam. CRP, PCT, and ESR levels are related to the severity of AECOPD complicated with pneumonia, and have value in evaluating the efficacy of piperacillin-tazobactam.

Antibiotic Stewardship in Treatment of Osteoarticular Infections Based on Local Epidemiology and Bacterial Growth Times.

Incubation for 14 days is recommended for the culture of microorganisms from osteoarticular infections (OAI), but there are no recommendations for postoperative antibiotic stewardship concerning empirical antimicrobial therapy (EAT), while prolonging broad-spectrum EAT results in adverse effects. The aim of this study was to describe the local OAI epidemiology with consideration of bacterial growth times to determine which antibiotic stewardship intervention should be implemented in cases of negative culture after 2 days of incubation. We performed a 1-year, single-center, noninterventional cohort study at the Pitié-Salpêtrière hospital OAI reference center. Samples were taken as part of the local standard of care protocol for adult patients who underwent surgery for OAI (native or device related) and received EAT (i.e., piperacillin-tazobactam plus daptomycin [PTD]) following surgery. The time to culture positivity was monitored daily. Overall, 147 patients were recruited, accounting for 151 episodes of OAI, including 112 device-related infections. Microbiological cultures were positive in 144 cases, including 42% polymicrobial infections. Overall, a definitive microbiological result was obtained within 48 h in 118 cases (78%) and within 5 days in 130 cases (86%). After 5 days, only Gram-positive bacteria were recovered, especially Cutibacterium acnes, Staphylococcus spp., and Streptococcus spp. Overall, 90% of culture-positive OAI were correctly treated with the locally established EAT. EAT guidance for OAI was in agreement with our local epidemiology. Our results supported antibiotic stewardship intervention consisting of stopping piperacillin-tazobactam treatment at day 5 in cases of negative culture. IMPORTANCE Osteoarticular infections (OAI) remain challenging to diagnose and to treat. One of the issues concerns postoperative empirical antimicrobial therapy (EAT), which is usually a combination of broad-spectrum antibiotics. This EAT is maintained up to 2 weeks, until the availability of the microbiological results (identification and drug susceptibility testing of the microorganisms responsible for the OAI). Our results provide new data that will help to improve OAI management, especially EAT. Indeed, we have shown that antibiotic stewardship intervention consisting of stopping the antibiotic targeting Gram-negative bacteria included in the EAT could be implemented in cases where culture is negative after 5 days of incubation. The benefits of such an antibiotic stewardship plan include improved patient outcomes, reduced adverse events (including Clostridioides difficile infection), improvement in rates of susceptibilities to targeted antibiotics, and optimization of resource utilization across the continuum of care.

Piperacillin/tazobactam-induced coagulopathy in a patient through a vitamin K-dependent mechanism

Haematologic side effects associated with piperacillin/tazobactam (PTZ) treatment are rare but can be fatal. The exact mechanism by which PTZ causes haemorrhages has not been determined. We report the case...

Outcomes analysis in patients with extended-spectrum beta-lactamase bacteremia empirically treated with piperacillin/tazobactam versus carbapenems

Infections caused by extended-spectrum beta-lactamase (ESBL)-producing bacteria are associated with worse outcomes and have limited treatment options. Carbapenems remain the drug of choice for these infections due to evidence of a mortality benefit and the mixed clinical efficacy associated with piperacillin/tazobactam (PTZ). Though definitive treatment for ESBL infections is well defined, evidence for appropriate empiric therapy remains inconclusive, and the role of rapid molecular assays that identify ESBL has not been evaluated. This multicenter retrospective study at nine Baylor Scott & White Health sites included patients who had positive blood cultures with ESBL-producing bacteria identified by rapid molecular assay and were empirically prescribed PTZ or carbapenems. A total of 117 patients were included in the study; 66 received empiric PTZ and 51 received carbapenems. Results showed no difference in hospital mortality (3% vs 7.8%, P = 0.4), hospital length of stay (6.1% vs 5.9%, P = 0.88), intensive care unit length of stay (4.7% vs 3.3%, P = 0.39), or recurrent ESBL bacteremia (7.6% vs 7.8%, P = 0.99) between the PTZ and carbapenem empiric treatment groups, respectively. In the era of rapid molecular assays, these results suggest that empiric PTZ use and avoidance of empiric carbapenem therapy in the first 24 hours of infection can be considered until a microbiological diagnosis is confirmed.

Pediatric acute kidney injury induced by concomitant vancomycin and piperacillin-tazobactam.

Vancomycin is very commonly used in combination with piperacillin-tazobactam (PTZ) as the initial empiric treatment for moderate-severe infection, whenever coverage for both methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa is required. The combination of vancomycin and PTZ in adults has recently been reported to significantly increase the risk of acute kidney injury (AKI) relative to vancomycin monotherapy; such reports in pediatrics, however, are sparse. A retrospective chart review was conducted of pediatric patients, aged 0-14 years, who were admitted to the general wards or intensive care unit and developed AKI after receiving vancomycin and PTZ concomitantly for >48h. AKI is defined as a decrease in estimated glomerular filtration rate ≥50% from baseline. Cases were identified by reviewing the Adverse Drug Reaction program database at King Saud University Medical City in Saudi Arabia from January 2015 to June 2016. Eight children admitted to the present hospital and who received concomitant vancomycin and PTZ treatment for pneumonia (n = 7) or febrile neutropenia (n = 1) developed drug-induced nephrotoxicity. Drug Interaction Probability Scale (DIPS) score for causation assessment was 9 in all cases (highly probable). Caution in utilizing the combination of vancomycin and PTZ is warranted in pediatric patients. Health-care professionals should be vigilant if this combination is to be initiated, and ensure close monitoring of renal function. Antibiotic therapy de-escalation should be considered as soon as culture results are available.

Clinical profile and successful outcomes of conservative and minimally invasive treatment of emphysematous pyelonephritis.

IntroductionEmphysematous pyelonephritis (EPN) is a rare clinical entity, characterized by gas in the renal system, due to an acute, fulminant and potentially fatal necrotizing process with varying clinical presentations. It is much more aggressive than uncomplicated pyelonephritis, with the mortality of 20–40% in the contemporary meta-analysis.Material and methodsA retrospective record review of inpatients at the Institute of Nephro Urology, Bangalore, India (2007–2014), who were treated after EPN was diagnosed with the aid of a CT (computed tomography) scan.ResultsSixty-six patients (M:F 27:39) treated for EPN over the past seven years with the mean (±SD) age of 52.32 (±12.48) years were analyzed. Median (interquartile range) duration of hospital stay was 8 (11.25) days with 4 (6%) patients requiring intensive care unit admission (median, IQR = 5.5, 1.5 days) of whom two passed away due to septicemia. Fifty-six (84.85%) patients were diabetics, forty (60.6%) patients had estimated glomerular filtration rate (eGFR) <60 ml/min/1.7 3 m2, 6 (9.1%) patients had eGFR <30 ml/min/1.73 m2 including 3 (4.5%) with eGFR <15 ml/min/1.73 m2 requiring hemodialysis and twenty-two (33%) had thrombocytopenia. Fifty (75.76%) patients were classified as Huang and Tseng Class 2, 7 (10%) as Class 3 with perinephric abscess requiring open drainage and 9 (13.64%) had bilateral EPN (Class 4). Majority (43; 65%) responded to piperacillin-tazobactam treatment. Double J stenting was done in 17 (25.76%) patients, percutaneous drainage in 5 (7.58%) patients and nephrectomy in 2 (3%) patients.ConclusionsAlthough EPN historically carries high morbidity and mortality, modern day medical management with timely intervention in the form of urinary drainage is effective and curative in most patients resulting in a low mortality rate.

Outpatient management of pediatric acute mastoiditis

ObjectiveEvaluate the Montreal Children's Hospital experience with outpatient management of uncomplicated acute mastoiditis with parenteral antibiotic therapy alone and determine if it is a safe alternative to inpatient management. Subjects and methodA retrospective review of pediatric patients diagnosed with acute mastoiditis at a tertiary care pediatric hospital between 2013 and 2015 was performed. Patients with syndromes, immunodeficiency, cholesteatoma, chronic otitis media, cochlear implant in the affected ear, or incidental mastoid opacity were excluded. Results56 children age 6 months to 15 years old were treated for acute mastoiditis, including 29 hospitalizations and 27 outpatients. Patients managed as outpatient with daily intravenous ceftriaxone had a 93% cure rate. Eighteen hospitalized and one outpatient had complications of acute mastoiditis. Children with complications were more likely to be febrile (p = 0.045). Two patients failed outpatient therapy and were admitted; one for myringotomy and piperacillin-tazobactam treatment and one required a mastoidectomy. 4/27 children treated as outpatient underwent myringotomy and tube insertion, 2 underwent myringotomy and tube along with admission and 21 did not require tube insertion. The average total duration of intravenous antibiotic therapy was respectively 4.9 and 18.9 days in the outpatient and hospitalized group. The average duration of admission was 5.9 days. ConclusionOutpatient medical therapy of uncomplicated pediatric mastoiditis is safe, successful, and efficient. Benefits include efficient use of surgical beds, cost savings and patient and family convenience. Careful patient selection and close monitoring are keys for successful outcome.

Effects of One-Week Empirical Antibiotic Therapy on the Early Development of Gut Microbiota and Metabolites in Preterm Infants

The early postnatal period is the most dynamic and vulnerable stage in the assembly of intestinal microbiota. Antibiotics are commonly prescribed to newborn preterm babies and are frequently used for a prolonged duration in China. We hypothesized that the prolonged antibiotic therapy would affect the early development of intestinal microbiota and their metabolites. To test this hypothesis, we analyzed the stool microbiota and metabolites in 36 preterm babies with or without antibiotic treatment. These babies were divided into three groups, including two groups treated with the combination of penicillin and moxalactam or piperacillin-tazobactam for 7 days, and the other group was free of antibiotics. Compared to the antibiotic-free group, both antibiotic-treated groups had distinct gut microbial communities and metabolites, including a reduction of bacterial diversity and an enrichment of harmful bacteria such as Streptococcus and Pseudomonas. In addition, there was a significant difference in the composition of gut microbiota and their metabolites between the two antibiotic-treated groups, where the piperacillin-tazobactam treatment group showed an overgrowth of Enterococcus. These findings suggest that prolonged antibiotic therapy affects the early development of gut microbiota in preterm infants, which should be considered when prescribing antibiotics for this population.

Targeted Metabolomics Analysis Identifies Intestinal Microbiota-Derived Urinary Biomarkers of Colonization Resistance in Antibiotic-Treated Mice.

Antibiotics excreted into the intestinal tract may disrupt the microbiota that provide colonization resistance against enteric pathogens and alter normal metabolic functions of the microbiota. Many of the bacterial metabolites produced in the intestinal tract are absorbed systemically and excreted in urine. Here, we used a mouse model to test the hypothesis that alterations in levels of targeted bacterial metabolites in urine specimens could provide useful biomarkers indicating disrupted or intact colonization resistance. To assess in vivo colonization resistance, mice were challenged with Clostridium difficile spores orally 3, 6, and 11 days after the completion of 2 days of treatment with piperacillin-tazobactam, aztreonam, or saline. For concurrent groups of antibiotic-treated mice, urine samples were analyzed by using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to quantify the concentrations of 11 compounds targeted as potential biomarkers of colonization resistance. Aztreonam did not affect colonization resistance, whereas piperacillin-tazobactam disrupted colonization resistance 3 days after piperacillin-tazobactam treatment, with complete recovery by 11 days after treatment. Three of the 11 compounds exhibited a statistically significant and >10-fold increase (the tryptophan metabolite N-acetyltryptophan) or decrease (the plant polyphenyl derivatives cinnamoylglycine and enterodiol) in concentrations in urine 3 days after piperacillin-tazobactam treatment, followed by recovery to baseline that coincided with the restoration of in vivo colonization resistance. These urinary metabolites could provide useful and easily accessible biomarkers indicating intact or disrupted colonization resistance during and after antibiotic treatment.

Randomized controlled trial of piperacillin-tazobactam, cefepime and ertapenem for the treatment of urinary tract infection caused by extended-spectrum beta-lactamase-producing Escherichia coli

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

Top Guns: The "Maverick" and "Goose" of Empiric Therapy.

Vancomycin and piperacillin-tazobactam are commonly used first guns in the empiric management of critically ill patients. Current studies suggest an increased prevalence of acute kidney injury with concomitant use, however, these studies are few and limited by small sample size. The purpose of this study was to compare the prevalence of nephrotoxicity after treatment with vancomycin alone and concomitant vancomycin and piperacillin-tazobactam treatment at our institution. Concomitant vancomycin and piperacillin-tazobactam-treated patients will experience greater prevalence of nephrotoxicity compared with vancomycin-only treated patients. This was a retrospective cohort of patients treated with vancomycin for gram-positive or mixed infections in our facility from 2005 to 2009 who were not receiving hemodialysis at the time of admission. Included patients were stratified by treatment with vancomycin, vancomycin/piperacillin-tazobactam, or vancomycin/an alternative gram-negative rod (GNR) antibiotic. p values for categorical variables were computed using χ(2) while continuous variables were computed using Kruskal-Wallis. Variables deemed statistically significant (< 0.05) were included in the multivariable, log-binomial regression model. Relative risk (RR) and 95% confidence intervals (CI), and p values were computed using a generalized estimating equation (GEE) approach with robust standard errors (i.e., Huber White "sandwich variance" estimates) to accommodate a correlated data structure corresponding to multiple episodes of infection per individual. A total of 530 patients with 1,007 episodes of infection, were treated with vancomycin (150 patients/302 episodes of infection), vancomycin/piperacillin-tazobactam (213 patients/372 episodes of infection), or vancomycin/GNR alternative (167 patients/333 episodes of infection). Patient demographics, comorbidities, sites of infection, and organisms of infection were compared among groups. After adjusting for statistically significant variables, neither vancomycin/piperacillin-tazobactam (RR = 1.1, 95% CI = 0.99-1.2; p = 0.073) nor vancomycin/GNR alternative (RR = 1.1, 95% CI = 0.98-1.2; p = 0.097) were found to be associated with an increased risk for nephrotoxicity compared with vancomycin alone. A difference in nephrotoxicity was not observed between vancomycin and vancomycin/piperacillin-tazobactam-treated patients at our institution. Concomitant use as empiric therapy is appropriate, although larger sample sizes are needed to analyze closely this relation among at-risk subsets of this population.

Serum Galactomannan Screening for Diagnosis of Invasive Pulmonary Aspergillosis in Children After Stem Cell Transplantation or with High-Risk Leukemia

Both transplanted and leukemia patients are at high risk (HR) for invasive pulmonary aspergillosis (IPA). Methods for rapid diagnosis are crucial. Our objective was to investigate the impact of serial serum galactomannan assay (GMA) screening on IPA diagnosis in children. Between January 2010 and December 2011, all children following stem cell transplantation (SCT) or with HR leukemia were prospectively included. Serum samples for GMA were taken once-twice weekly. Results >.5 were considered positive. Patients suspected of having IPA were stratified as possible, probable, and definite. Forty-six children (median age, 8 years) were included, 38 after SCT (32 allogeneic), 8 with HR leukemia. A total of 510 samples were taken; screening period was 1–6 months for 34 patients. GMA was negative in 28 patients, all but one without suspicion of IPA. Eighteen patients had positive GMA: while four (22%) were upgraded to probable IPA, fourteen (78%) were considered as false positives (FP), some associated with piperacillin-tazobactam treatment. GMA sensitivity and specificity were 0.8 and 0.66, respectively; positive- and negative-predictive values (PPV, NPV) were 0.22 and 0.96, respectively. GMA may have a role in evaluating HR children for IPA. Both NPV and FP rates are high. The cost benefit of early detection versus over-diagnosis should be further studied.

A Comparative Study of Piperacillin-Tazobactam With and Without Vancomycin as Empirical Therapy for Febrile Neutropenic Patients With Solid Tumor Malignancies.

BackgroundThe objective of this study was to evaluate the outcomes, mortality and toxicity associated with piperacillin-tazobactam (PT) and the addition of vancomycin (VM) to the empirical treatment of febrile neutropenic cancer patients.MethodA retrospective study on adult febrile neutropenic patients who were admitted between September 2008 and May 2013 with solid tumor malignancies was conducted at King Fahad Specialist Hospital Dammam, Saudi Arabia.ResultsOut of 86 febrile neutropenic patients, 60 patients were treated with PT group and 26 patients were with PT + VM group. The two groups were comparable in terms of outcome, mortality, nephrotoxicities and hepatotoxicities. The median duration of neutropenia in PT treatment group was 4 days (range 1 - 10) in the female and 7 days (range 1 - 13) in males while in PT + VM 6 days (range 1 - 5) in female and 7.5 days (range 1 - 6) in male with significance P = 0.007. There was no significant difference in terms of duration of fever and length of stay between the two treatment groups. There were no deaths reported during treatment in both groups. In PT, the microbial eradication was 27/40 (67.5%) patients (14/27 (51.9%) of female and 13/27 (48.1%) of male)), whereas it was 13/40 (32.5%) patients (9/13 (69.2%) of female and 4/13 (30.8%) of male)) in PT + VM group. Overall, there was no significant difference in terms of microbiological eradication between the two groups (OR: 1.22; 95% CI: 0.486 - 3.072; X2 stat: 0.182; P = 0.67). Response to therapy in clinically defined infections was higher 16/23 (69.56%) in PT treatment group than 7/23 (30.44%) in PT + VM group. But there was no significant difference between the two treatment groups in terms of clinically defined infections (OR: 1.013; 95% CI: 0.359 - 2.862; X2 stat: 0.001; P = 0.98). There was no significant difference in renal and liver functions between the two groups in terms of serum creatinine level and clearance, alkaline phosphate and alanine tranferase and gama glutamyl tranferase. The most commonly isolated organisms were Escherichais coli (eighteen isolates), Staphylococcus aureus (seven isolates), Streptococcus spp (six isolates) and Klebsiella pneumonia (four isolates). The overall success rate was similar in both treatment arms and treatment was well tolerated, with no severe adverse reactions reported.ConclusionAlthough the addition of VM might provide an additional value for coverage of gram-positive pathogens. This study demonstrates that there was no significant difference in terms of response rate in both treatment groups, which could be due to the low local methicillin-resistant Staphylococcus aureus (MRSA) rates and other resistant gram-positive organisms at our institution, stressing the importance of local antibiograms in developing empirical neutropenic fever protocols.

Unexpected complication of intralesional injection of recombinant human epidermal growth factor: diabetic foot osteomyelitis

Dear Editors, A 66-year-old patient with type 2 diabetes mellitus of 13 years duration was referred to the Undersea and Hyperbaric department because of a swollen infected big toe that occurred during the course of intralesional parenteral epidermal growth factor (IP-EGF) treatment. The patient had a chronic non-healing plantar ulcer over the metatarsal head of the first toe for almost 5 years (Figure 1). He was scheduled to receive IP-EGF three times a week for 4weeks, but experienced complication following the third application. The treatment was stopped and the patient was referred for consultation. The patient had hypertension, congestive heart failure and chronic renal failure. On examination his peripheral pulses were impalpable and he had severe loss of foot sensation. The big toe was significantly swollen with increased temperature and marked hyperaemia (Figure 2). An X-ray showed osteomyelitis of the metatarsal head and phalanges of the hallux (Figure 3). The patient was hospitalised and received parenteral piperacillin–tazobactam treatment 4.5mg/kg three times a day for 3weeks. IP-EGF is a lyophilised formulation comprising human recombinant (rH-EGF). It has been introduced as a relatively safe drug with promising outcomes in the treatment of diabetic foot ulcers (1–3). The major concern regarding intralesional wound injections, however, is that they may have the potential to drive the superficial infection, as in our case, to deeper tissues. Alternate treatment opportunities other than intralesional approaches may be a rational approach to prevent such complications. In case of an absolute indication, changing the needle

Postoperative Stevens-Johnson syndrome secondary to piperacillin-tazobactam: A case report

Introduction: Toxic epidermal necrolysis (TEN) and Stevens–Johnson syndrome (SJS) are severe, potentially fatal cutaneous reactions to medications affecting only 1–2 per million individuals each year. They present as tenderness, erythema and blistering of both the skin and mucus membranes. We describe a case of Stevens–Johnson syndrome linked to piperacillin–tazobactam treatment, which is a previously unreported cause and a rare occurrence in postoperative patients. Case Report: A 37­year­old female with chronic pancreatitis post­total pancreatectomy with auto­islet transplant was re­admitted on postoperative day 12 with abdominal pain and leukocytosis. Her workup revealed a small intra­ abdominal fluid collection suspicious for an abscess and she was empirically started on piperacillin–tazobactam. She developed hives on her extremities with associated itching after four days of treatment. Piperacillin–tazobactam was discontinued, diphenhydramine was administered for symptomatic relief, and she was discharged on an oral regimen of ciprofloxacin and metronidazole. She returned the following day with a rash extending onto her chest, abdomen, feet, face, lips and mouth, with newly appeared bullae covering approximately 35–50% of body surface. A skin biopsy was consistent with SJS, with piperacillin–tazobactam identified as the likely causative agent. Conclusion: The most common medications linked to TEN/SJS are sulfonamide antibiotics (especially sulfamethoxazole/trimethoprim), cephalosporins, quinolones, allopurinol, carbamazepine, phenytoin, phenobarbital, and NSAIDs (oxicam­type). While medications the most common cause, mycoplasma pneumoniae and herpes simplex virus (HSV) have also been linked to SJS. The mortality rate of biopsy­ confirmed SJS ranges from 1–5%, whereas the mortality of TEN ranges from 25–35%. Though many patients experience pruritis and/or rashes as side­effects to medications given post­ operatively, it is important to keep in mind more serious reactions such as TEN and SJS as these conditions as they have a substantial associated morbidity and even mortality.

Assessment of Susceptibility, Pharmacodynamics, and Therapeutic Response for Interpretation of Piperacillin-Tazobactam &amp;lt;i&amp;gt;in Vitro&amp;lt;/i&amp;gt; Activity in the Treatment of &amp;lt;i&amp;gt;Pseudomonas aeruginosa&amp;lt;/i&amp;gt; Infection

Pseudomonas aeruginosa remains an important pathogen. Our purpose was to determine the minimum inhibitory con-centration (MIC) and pharmacodynamic (PD) parameters predicting a positive response to therapy with piperacil-lin-tazobactam. Medical records were retrospectively reviewed at 3 centers. Data were recorded to assess age, type of disease, renal function, weight (body mass), MIC, antimicrobial treatment, and clinical outcome. Success was response to piperacillin-tazobactam alone, or in combination with another active agent; failure was lack of response. Of 78 eva-luable patients, 63 responded (7 UTI; 56 non-UTI) and 15 did not; 26 responding received combination therapy and 37 monotherapy. Piperacillin-tazobactam treatment was successful in 53 of 63 of non-UTI disease with a MIC of ≤64/4 μg/mL, but in only 3 of 7 with a MIC of >64/4 μg/mL (P = 0.023); overall 9 of 10 infections by strains with MICs = 32 - 64 μg/mL had a successful outcome. Piperacillin estimated time above MIC at 20% separated those responding from those that did not (P = 0.019).

False positive galactomannan Platelia due to piperacillin-tazobactam

Introduction Invasive aspergillosis is a serious disease, the lethality of which is important among hematology patients. Early diagnosis is crucial for treatment options and the prognosis. Detection of the antigen galactomannan is the most frequently used microbiological tools. But galactomannan detection may be falsely positive, and this false positivity has been associated with piperacillin-tazobactam treatment, the main antibiotic combination used in clinical hematology. Objective The purpose of our study, carried out from January 2009 to December 2010 at the Versailles hospital on in-patients with hematological disorders, was to evaluate the association between false galactomannan positivity and administration of piperacillin-tazobactam, and to study a possible variability of products issued by three manufacturers. Patients and method We noted that 207 patients were included ( n = 207), accounting for 69 false positive and 138 true negative results. The intrinsic galactomannan values in the study were sensitivity 100%, specificity 68%, positive and negative predictive values respectively 16%, 100%, and a likelihood positive and negative test at respectively 3.12, and 0. Results The statistical analysis did not determine any association between false positivity in galactomannan and piperacillin-tazobactam issued by two manufacturers ( P = 0.87 and P = 0.94). But, there was a significant association between false galactomannan positivity and piperacillin-tazobactam issued by the third manufacturer ( P = 0.02). Four of the 25 batches issued by this manufacturer were tested and negative “in vitro” for galactomannan. Discussion This study results suggest that the association between false galactomannan positivity and piperacillin-tazobactam is not longer systematic, but can still prevail depending on the manufacturers. It also confirmed the positive contribution of testing piperacillin-tazobactam batches “in vitro” before using the antibiotic.

Cholangitis with septic shock caused by Raoultella planticola

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

Systematic Review of Piperacillin-Induced Neutropenia

Because penicillin agents are implicated in granulopoiesis inhibition, healthcare professionals frequently consider discontinuation of such therapy in patients with decreasing white blood cell counts. No systematic review to date has described piperacillin and the patient population at risk for this adverse drug reaction (ADR). This review sought to assess the occurrence of piperacillin-induced neutropenia, describe characteristics of affected patients and assess the reporting modalities that most accurately classify this ADR. Case reports, cohort studies and clinical trials identified by comprehensive searches of PubMed and the US FDA Adverse Event Reporting System (AERS) database were reviewed for patient demographics, duration and dose of piperacillin or piperacillin-tazobactam treatment and the occurrence of neutropenia. Causality assessments were performed. Six published case reports, three cohort studies, 178 clinical trials and two compilations of phase I-III trials were reviewed. Review of case reports was notable in that the duration of beta-lactam therapy prior to the noting of leukopenia always exceeded 15 days. No deaths were recorded in this group. Among 13,816 patients enrolled in non-neutropenic fever studies, the occurrence of piperacillin-induced neutropenia was rare: five patients (0.04%) developed neutropenia; none died. The demographics for this group were poorly documented. Through the AERS database, we identified 366 unique cases of piperacillin or piperacillin-tazobactam-induced haematological abnormalities, including neutropenia (n = 183, 50.0%), leukopenia, (n = 99, 27%), agranulocytosis (n = 58, 15.8%) and others. In 62 cases, patients received between 1 and 14 days of therapy (mean 7.7 + 4.1 days). Overall, there were 82 (22.4%) deaths. Reports of haematological ADRs among patients receiving piperacillin or piperacillin-tazobactam are rare. Report of neutropenia associated with piperacillin usage prior to 15 days of therapy is a novel finding that requires further evaluation. Current reporting methods poorly characterise patient groups at risk.