A targeted likelihood estimation comparing cefepime and piperacillin/tazobactam in critically ill patients with community-acquired pneumonia (CAP).

Cefepime and piperacillin/tazobactam are antimicrobials recommended by IDSA/ATS guidelines for the empirical management of patients admitted to the intensive care unit (ICU) with community-acquired pneumonia (CAP). Concerns have been raised about which should be used in clinical practice. This study aims to compare the effect of cefepime and piperacillin/tazobactam in critically ill CAP patients through a targeted maximum likelihood estimation (TMLE). A total of 2026 ICU-admitted patients with CAP were included. Among them, (47%) presented respiratory failure, and (27%) developed septic shock. A total of (68%) received cefepime and (32%) piperacillin/tazobactam-based treatment. After running the TMLE, we found that cefepime and piperacillin/tazobactam-based treatments have comparable 28-day, hospital, and ICU mortality. Additionally, age, PTT, serum potassium and temperature were associated with preferring cefepime over piperacillin/tazobactam (OR 1.14 95% CI [1.01-1.27], p = 0.03), (OR 1.14 95% CI [1.03-1.26], p = 0.009), (OR 1.1 95% CI [1.01-1.22], p = 0.039) and (OR 1.13 95% CI [1.03-1.24], p = 0.014)]. Our study found a similar mortality rate among ICU-admitted CAP patients treated with cefepime and piperacillin/tazobactam. Clinicians may consider factors such as availability and safety profiles when making treatment decisions.

Population Pharmacokinetic Model of Piperacillin in Critically Ill Patients and Describing Interethnic Variation Using External Validation.

Objectives: This study aimed to develop a piperacillin population PK model for critically ill Brazil-ian patients and describe interethnic variation using an external validation. Methods: Plasma samples were obtained from 24 ICU patients during the fifth day of piperacillin treatment and assayed by HPLC-UV. Population pharmacokinetic modelling was conducted using Pmetrics. Empiric dose of 4 g IV 6- and 8-hourly were simulated for 50 and 100% fT > MIC and the probabil-ity of target attainment (PTA) and the fractional target attainment (FTA) determined. Results: A two-compartment model was designed to describe the pharmacokinetics of critically ill Brazillian patients. Clearance and volume of distribution were (mean ± SD) 3.33 ± 1.24 L h−1 and 10.69 ± 4.50 L, respectively. Creatinine clearance was positively correlated with piperacillin clearance and a high creatinine clearance was associated with lower values of PTA and FTA. An external vali-dation was performed using data from two different ethnic ICU populations (n = 30), resulting in acceptable bias and precision. Conclusion: The primary pharmacokinetic parameters obtained from critically ill Brazilian patients were similar to those observed in studies performed in critically ill patients of other ethnicities. Based on our results, the use of dose adjustment based on creati-nine clearance is required in Brazilian patients.

Exantema intertriginoso y flexural simétrico por fármacos: presentación de un caso / Symmetrical drug-related intertriginous and flexural exanthema: a case report

Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) is a benign, self-limited, immune-mediated, symmetric erythematous rash involving the buttocks and other intertriginous/flexural areas, observed after systemic exposure to a drug in an individual with or without prior sensitization. We present a 70-year old patient, who presented SDRIFE after the administration of piperacillin-tazobactam which improved rapidly after its suspension.

El exantema intertriginoso y flexural simétrico relacionado con fármacos (SDRIFE, por su sigla en inglés) es una erupción eritematosa simétrica, inmunomediada, benigna y autolimitada, que compromete glúteos y otras áreas intertriginosas, flexurales o ambas, y que se observa luego de la exposición sistémica a un fármaco en un individuo con sensibilización previa o sin ella. Se comenta el caso clínico de un paciente de 70 años de edad, que presentó SDRIFE posterior a la administración de piperacilina-tazobactam y que mejoró rápidamente luego de su suspensión.

Efetividade da infusão estendida de Piperacilina-tazobactana - Meropenem no tratamento de pacientes sépticos adultos queimados através da modelagem farmacocinética farmacodinâmica, PK/P / Meropenem and piperacillin/tazobactam by extended infusion and PK/PD approach for drug effectiveness

Introdução: Meropenem (MER) e Piperacilina/Tazobactana (PTZ) são agentes antimicrobianos largamente prescritos para pacientes grandes queimados internados em Unidade de Terapia Intensiva (UTI) com infecções nosocomiais causadas por Gram-negativos sensíveis CIM 2 mg/L, Enterobacteriaceae, EB e Non-enterobacteriaceae, NEB. A síndrome da resposta inflamatória sistêmica (SRIS) que ocorre durante o choque séptico no grande queimado pode causar alteração na farmacocinética do paciente em terapia intensiva, de modo que a dose recomendada pode não atingir o alvo desejado contra Gram-negativos de sensibilidade intermediária CIM >2 mg/L. Objetivo: Investigar a efetividade dos beta-lactâmicos piperacilina e meropenem na infusão estendida comparada à infusão intermitente recomendada, para os pacientes sépticos grandes queimados através da abordagem farmacocinética-farmacodinâmica (PK/PD). Ética, casuística e procedimentos: Autor e co-autores declararam não haver conflito de interesse. O protocolo foi aprovado, registro CAAE 07525118.3.0000.0068. No presente protocolo de estudo investigaram-se 36 pacientes sépticos grandes queimados, ambos os gêneros (12F/24M) em terapia intensiva do choque séptico com piperacilina-tazobactana 4,5g q6h ou meropenem 1g q8h. Os pacientes incluídos foram estratificados em dois grupos com base na administração através da infusão intermitente, 0,5 h (G1) ou da infusão estendida, 3 h (G2), ambos com 16 pacientes cada. Duas amostras sanguíneas (1,5mL/cada) foram coletadas no estado de equilíbrio (Steady State), 3ª e 5ª hora do início da infusão. Os níveis séricos de PTZ e MER foram mensurados através de cromatografia líquida, e a farmacocinética (PK) dos dois grupos de pacientes foi comparada aos dados reportados em voluntários sadios. A abordagem PK/PD foi aplicada para avaliação da cobertura do antimicrobiano a partir da estimativa do índice de predição de efetividade (% fΔT>CIM) e da probabilidade de alcançar o alvo terapêutico (PTA) com base no alvo PK/PD recomendado, 100%fΔT>CIM. Resultados e discussão: As características de admissão dos pacientes G1/G2 foram expressas através de mediana e interquartil: Clcr 115 (90-148) / 127 (90-170) ml/min; 30 (24-31) / 27 (24- 33,5) anos, 70 (61-75) / 71 (65-75) kg, 30 (20-42) / 33,9 (18-38,4)% área total de superfície queimada, SAPS3 53 (45-57) / 48 (37,8-59,5). Na admissão dos pacientes na UTI registrou-se G1/G2: trauma térmico (17/16), trauma elétrico (1/2), lesão inalatória (11/11), ventilação mecânica (16/9) e vasopressores foram necessários em 15/8 pacientes, G1/G2. Ocorreram diferentes alterações na farmacocinética dos dois beta-lactâmicos após a infusão estendida versus a infusão intermitente quando comparadas com dados relatados em voluntários sadios. Evidenciou-se prolongamento da meia vida decorrente do aumento do volume de distribuição. Estes resultados impactaram diferentemente a cobertura. O monitoramento de biomarcadores inflamatórios expressos em medianas (G1/G2) evidenciou aumento do PCR: 232/183mg/L e leucocitose (leucócitos 11/14 mil cel/mm3, neutrófilos 9/10 mil cel/mm3) na fase precoce do choque séptico. Relativamente à microbiologia dos isolados, a erradicação dos patógenos ocorreu para todos os pacientes após a infusão estendida contra Gram-negativos sensíveis (CIM: 2 mg/L), e de sensibilidade intermediária (CIM 4mg/L) como a K. pneumoniae e P. aeruginosa, enquanto a infusão intermitente garantiu erradicação de patógenos apenas até CIM 2 mg/L. Conclusão: Evidenciou-se a superioridade da infusão estendida frente à infusão intermitente na cobertura dos dois antimicrobianos, no alvo terapêutico considerado 100%fΔT>CIM. Registraram-se alterações na farmacocinética destes agentes nos pacientes frente aos dados reportados para voluntários sadios. Diferença significativa entre grupos (G1/G2) foi encontrada com relação meia vida biológica, e ao volume de distribuição tanto pata a piperacilina quanto para o meropenem

Background: Meropenem (MER) and Piperacillin/Tazobactam (PTZ), antimicrobial betalactam agents are widely prescribed to burn patients from the Intensive Care Unit (ICU) with nosocomial infections caused by Gram-negative strains. Change in the pharmacokinetics of critically ill patient occurs during the systemic inflammatory response syndrome (SIRS) at the course of septic shock. Then, the recommended dose administered by intermittent infusion, 0.5 hr cannot reach the target against gram-negative strains MIC > 2 mg/L. Subject: To investigate drug effectiveness of the beta-lactams piperacilin and meropenem in extended infusion compared to the recommended intermittent infusion in critically ill septic burn patients using pharmacokinetic-pharmacodynamic (PK/PD) approach. Ethics, Casuistry and Methods: All authors declared there is no conflict of interests. Ethical approval CAAE, register 07525118.3.0000.0068. It was investigated in the study protocol 36 septic burn patients of both genders (12M / 24F), undergoing antimicrobial therapy with PTZ 4.5 g q6h or MER 1g q8h. Based on the chosen antimicrobial therapy and drug infusion prescribed by the physician, patients were stratified in groups with intermittent 0.5h infusion (G1) or with the extended 3h infusion (G2), both groups with 16 patients each. Two blood samples were collected at the steady state (1.5mL / each), at the 3rd and 5th hrs of starting the infusion. Serum levels were measured by liquid chromatography. Pharmacokinetics (PK) of MER or PTZ was compared to data reported in healthy volunteers for both groups of patients. PK/PD approach was applied to estimate the drug effectiveness index (fΔT> MIC) and to assess the probability of target attained (PTA) based on the recommended PK/PD target, 100% fΔT> MIC. Results and discussion: Characteristics of patients admission G1/G2 were: Clcr 115(90- 148)/127(90-170) ml/min; 30(24-31)/27(24-34) yrs, 70(61-75)/71(65-75) kg, 30(20- 42)/33.9(18-38.4)% total burn surface area, SAPS3 53(45-57)/48(37.8-59.5), medians (interquartile): thermal trauma occurred (17/16), electric trauma (1/2), inhalation injury (11/11), mechanical ventilation (9/16) and vasopressors required in 15/8 patients. It was demonstrated that different PK changes occurred for both beta-lactam agents after the extended or intermittent infusion by comparison with data reported in healthy volunteers. PK changes were related to the prolongation of biological half-life and increases on volume of distribution with impact on pharmacodynamics. On the other hand, meropenem total body clearance reduced by 50% at the earlier period of septic shock could be explained by the reduction of MER-transporters expression in the tubular renal secretion, once only patients with renal function preserved were included in the study protocol. Inflammatory biomarkers increased at the earlier period of septic shock: C-rp 232/183mg/L; leukocytes 11/14*103cel/mm3, neutrophils 9/10*103cel/mm3, medians, G1/G2. Clinical and microbiological cure was obtained for all patients of G1 against MIC < 2mg/L after intermittent 0.5 h infusion; while PK/PD target was attained for G2 patients undergoing antimicrobial therapy with MER or PTZ by extended infusion against gram negative strains K. pneumoniae, P. aeruginosa up to MIC 4mg L. Conclusion: Superiority of the extended infusion over intermitent infusion was obtained for the two antimicrobials was evidenced, in the therapeutic target considered 100%fΔT>CIM. Changes in the pharmacokinetics of these agents were recorded in patients compared to data reported for healthy volunteers. A significant difference between groups (G1/G2) was found in relation to biological half-life and volume of distribution for both piperacillin and meropenem

Evaluation of the effect of antibiotics used during parenteral nutrition treatment on Candidemia

SUMMARY OBJECTIVE: Parenteral nutrition is an important risk factor for candidemia. In this risk analysis study, the effect of previous antibiotic administration apart from the length of hospital stay, duration of Parenteral nutrition treatment, and Candida score parameters on developing candidemia was evaluated in the non-neutropenic patients receiving Parenteral nutrition treatment. METHODS: In this double center, retrospective, and cross-sectional study, the data of patients who received Parenteral nutrition treatment were collected. Patients with or without candidemia after the initiation of Parenteral nutrition treatment were compared in terms of demographic features, Candida score, length of hospital stay, duration of Parenteral nutrition treatment, and previous use of antibiotics. Then, predictor factors affecting the probability of candidemia during Candida growth time were determined by the Cox regression analysis. RESULTS: A total of 148 patients (59.5% males) were included and 16 (10.81%) of these had candidemia after initiation of parenteral nutrition treatment. The median (min-max) duration of parenteral nutrition treatment was 11 (4-72) days and the Candida growth time was 13 (7-29) days. Statistically significant differences were found between patients with or without candidemia groups in terms of length of hospital stay (p<0.001), duration of parenteral nutrition treatment (p<0.001), and Candida score (p<0.001). To determine the effect of these variables and antibiotics on candidemia, length of hospital stay [Hazard Ratio 1.030; p=0.021] and piperacillin-tazobactam (Hazard Ratio 5.626; p=0.030) were found significant and independent risk factors on the development of candidemia. CONCLUSION: There are some well-known risk factors including length of hospital stay, duration of Parenteral nutrition treatment, and Candida score; the potential impact of piperacillin-tazobactam administration should also be considered since they may be effective on the development of candidemia.

Risk Factors of Death in Bloodstream Infections Caused by AmpC ß-Lactamase-Producing Enterobacterales in Patients with Neoplasia.

PURPOSE: The infections caused by ESCPM Enterobacterales (Enterobacter spp., Serratia spp., Citrobacter spp., Providencia spp. and Morganella spp.) have limited therapeutic options. Patients with neoplastic diseases are particularly vulnerable to bloodstream infections (BSIs). OBJECTIVE: To analyze determinant factors of death in patients with neoplasia complicated with BSI caused by ESCPM Enterobacterales. PATIENTS AND METHODS: A cohort study of patients aged 18 years or older with neoplasia and BSI due to ESCPM group was conducted at the Cancer Hospital I of the National Cancer Institute, Brazil, from September 2012 to December 2017. The variables associated with death were analyzed using multivariate logistic regression. RESULTS: Of the 103 patients included in the cohort, 67.0% were male, the median age was 63 years and 67.0% had solid tumors. Of the 107 BSI episodes evaluated, 70.1% were hospital-acquired infections, 54.2% were secondary to extravascular focus of infection, gastrointestinal tract (19.6%), mainly. Enterobacter spp. (n: 49, 45.4%) was the most frequent agent isolated followed by Serratia spp. (n: 34, 31.5%), Morganella morganii (n: 16, 14.9%), Citrobacter freundii. (n: 7, 6.5%) and Providencia spp. (n: 2, 1.8%). Ten (9.3%) BSI episodes were caused by multidrug-resistant ESCPM Enterobacterales (MDR-ESCPM). The 7-day and 30-day mortality were 9.3% and 21.5%, respectively. The BSIs caused by MDR-ESCPM were independently associated with 7-day death (OR = 21.62 95% CI: 1.81-258.51 P = 0.01). Monotherapy with piperacillin-tazobactam tended to be associated with 7-day death (OR = 10.46 95% CI: 0.97-112.91 P = 0.05) and 30-day death (OR = 2.73 95% CI: 0.96-7.70 P = 0.05). CONCLUSION: BSIs due to ESCPM group have high mortality and when caused by MDR-ESCPM are independently associated with 7-day death. The possible association of piperacillin-tazobactam monotherapy for BSI-ESCPM with death needs to be better studied.

Eficacia y seguridad del tratamiento empírico con piperacilina/tazobactan como monoterapia en episodios de neutropenia y fiebre en niños con cáncer: revisión sistemática y meta-análisis / Efficacy and safety of empirical treatment with piperacillin/tazobactan as monotherapy in episodes of neutropenia and fever in children with cancer: systematic review and meta-analysis

INTRODUCCIÓN: La neutropenia febril en niños con patología oncohematològica requiere un tratamiento empírico precoz y adecuado. Esta revisión sistemática se realizó para evaluar si piperacilina/tazobactam (PTZ) monoterapia es más efectiva y segura que los comparadores, en niños con episodios de neutropenia febril de causa oncológica. MATERIAL Y MÉTODOS: Se realizó una búsqueda bibliográfica en Embase, MEDLINE utilizando los términos de búsqueda (('febrile neutropenia' OR hemato oncology OR haemato oncology OR 'immunocompromised host' OR 'immunocompromised patient' OR 'chemotherapy-induced febrile neutropenia') AND (piperacillin OR tazobactam OR 'piperacillin plus tazobactam' OR 'piperacillin/tazobactam' OR 'piperacillin-tazobactam' OR tazocin OR 'piperacillin-tazobactam drug combination')). El criterio de valoración de eficacia fue la incidencia de fracaso terapéutico. El punto final de seguridad fue la ausencia de cualquier efecto adverso (EA). RESULTADOS: Se identificaron 1.388 estudios, de los cuales se incluyeron 11 que cumplían los criterios de elegibilidad. Los estudios presentaron notable homogeneidad ( I 2 0%) y no se detectó sesgo de publicación (p 0,36). El riesgo de fracaso terapéutico de PTZ no fue mayor que en los comparadores (RR global: 0,94; IC95% 0,83 a 1,07) como tampoco lo fue, la incidencia de EA. CONCLUSIONES: El riesgo de fracaso terapéutico no fue superior para la PTZ como monoterapia frente a los comparadores

BACKGROUND: Febrile neutropenia in children with onco-hematological diseases is an important cause of morbidity and mortality and requires early and adequate empirical treatment. This systematic review was conducted to evaluate if piperacillin/ tazobactan (PTZ) monotherapy leads to a lower incidence of therapeutic failures than comparators. METHODS: A literature search was carried out in Embase, and MEDLINE databases using the search terms ('febrile neutropenia' OR hemato oncology OR haemato oncology OR 'immunocompromised host' OR 'immunocompromised patient' OR 'chemotherapy-induced febrile neutropenia') AND (piperacillin OR tazobactam OR 'piperacillin plus tazobactam' OR 'piperacillin/tazobactam' OR 'piperacillin-tazobactam' OR tazocin OR 'piperacillin-tazobactam drug combination')), Efficacy endpoint was treatment failure rate. The safety end-point was absence of any adverse effects (AE). RESULTS: Eleven studies were included. No heterogeneity was detected ( I 2 0%). The risk of failure was not superior for piperacillin/tazobactan to comparators (Global RR: 0.94; IC95% 0.83 a 1.07). Rates of adverse events were similar among studies. No publication bias was detected (p 0.36). CONCLUSIONS: This systematic review and meta-analysis showed that treating episodes of febrile neutropenia in oncology pediatric patients, the risk of failure for PTZ was not superior to comparators. Adverse events were similar to the comparators.

Beta-lactams susceptibility testing of penicillin-resistant, ampicillin-susceptible Enterococcus faecalis isolates: a comparative assessment of Etest and disk diffusion methods against broth dilution.

This study aimed to evaluate the accuracy of disk diffusion and Etest methods, compared to that of the broth dilution reference method for identifying beta-lactam susceptibilities of Penicillin-Resistant, Ampicillin-Susceptible Enterococcus faecalis (PRASEF) isolates. Fifty-nine PRASEF and 15 Penicillin-Susceptible, Ampicillin-Susceptible E. faecalis (PSASEF) clinical nonrepetitive isolates were evaluated. The effectiveness of five beta-lactams (ampicillin, amoxicillin, imipenem, penicillin, and piperacillin) was tested. All antimicrobial susceptibility tests were performed and interpreted according to the Clinical and Laboratory Standards Institute guidelines. Interpretative discrepancies, such as essential agreement, categorical agreement, and errors, were assessed. The acceptability was ≥ 90% for both categorical agreement and essential agreement. Etest proved to be an accurate method for testing beta-lactam susceptibilities of the emerging PRASEF isolates, disk diffusion presented poor performance, particularly for imipenem and piperacillin.

Concentraciones plasmáticas de piperacilina/tazobactam en pacientes pediátricos críticos sometidos a ECMO: análisis preliminar / Plasmatic concentracion of piperacillin/tazobactam in pediatric patients on ECMO support: preliminary analysis

Resumen Introducción: Se desconocen las alteraciones farmacocinéticas de piperacilina/tazobactam (PT) en pacientes pediátricos que requieren de membrana de oxigenación extracorpórea (ECMO) y cómo dosificar adecuadamente dicho antimicrobiano. Objetivo: Describir las concentraciones plasmáticas (CP)y evaluar el cumplimiento del objetivo farmacocinético/famacodinámico de piperacilina en pacientes pediátricos en soporte con ECMO. Métodos: Presentamos tres pacientes pediátricos en tratamiento con PT que requirieran de ECMO en los que se midieron CP de piperacilina en la mitad del intervalo de dosificación mediante cromatografía liquida de alta resolución. Resultados: Las CP fueron 51,7-14,1 y 6,5 μg/mL para los pacientes A, B y C, respectivamente. Sólo se alcanzaron CP adecuadas en un paciente. Conclusión: Estos resultados preliminares sugieren que la disponibilidad de CP de piperacilina podría optimizar el cumplimiento de los objetivos farmacocinéticos/farmacodinámicos en pacientes pediátricos en soporte con ECMO.

Abstract Background: Pharmacokinetics and optimal dosing of piperacillin tazobactam (PT) have not been well studied in pediatric patients undergoing extracorporeal oxygenation membrane (ECMO). Aim: To describe piperacillin plasmatic concentration and evaluate achievement of pharmaccokinetic/pharmacodinamic objective in patients on ECMO support. Method: We report three pediatric patients admitted to the Pediatric Intensive Care Unit, treated with PT undergoing ECMO. Plasmatic concentrations of piperacillin were obtained in the middle of the dosing interval using high performance liquid chromatography. Results: Plasmatic concentrations were 51,7-14,1 and 6,5 μg/mL for patient A, B and C respectively. Only one patient reached adequate concentrations. Conclusion: These preliminary results suggest that availability of plasmatic concentrations of piperacillin could optimize the achievement of pharmacokinetic/pharmacodynamic objectives in pediatric patients on ECMO support.

Linguistic and cultural adaptation to the Portuguese language of antimicrobial dose adjustment software / Adaptação linguística e cultural para a língua portuguesa de um software para ajuste de dose de antimicrobianos

ABSTRACT Objective To adapt an antibiotic dose adjustment software initially developed in English, to Portuguese and to the Brazilian context. Methods This was an observational, descriptive study in which the Delphi method was used to establish consensus among specialists from different health areas, with questions addressing the visual and operational aspects of the software. In a second stage, a pilot experimental study was performed with the random comparison of patients for evaluation and adaptation of the software in the real environment of an intensive care unit, where it was compared between patients who used the standardized dose of piperacillin/tazobactam, and those who used an individualized dose adjusted through the software Individually Designed and Optimized Dosing Strategies. Results Twelve professionals participated in the first round, whose suggestions were forwarded to the software developer for adjustments, and subsequently submitted to the second round. Eight specialists participated in the second round. Indexes of 80% and 90% of concordance were obtained between the judges, characterizing uniformity in the suggestions. Thus, there was modification in the layout of the software for linguistic and cultural adequacy, minimizing errors of understanding and contradictions. In the second stage, 21 patients were included, and there were no differences between doses of piperacillin in the standard dose and adjusted dose Groups. Conclusion The adapted version of the software is safe and reliable for its use in Brazil.

RESUMO Objetivo Adaptar um software de ajuste de dose de antibióticos inicialmente elaborado em língua inglesa para o português e a conjuntura brasileira. Métodos Trata-se de estudo observacional, descritivo, em que foi utilizado o método Delphi para estabelecer consenso entre especialistas de diferentes áreas da saúde, com perguntas que abordaram os aspectos visuais e operacionais do software. Em uma segunda etapa, foi realizado um estudo piloto, experimental, com alocação aleatória dos pacientes, para avaliação e adaptação do software em ambiente real de uma unidade de tratamento intensivo, onde foram comparadas diferenças entre pacientes que utilizaram dose padronizada usual de piperacilina/tazobactam, e os que utilizaram a dose individualizada ajustada por meio do software Individually Designed Optimum Dosing Strategies. Resultados Participaram da primeira rodada 12 profissionais cujas sugestões foram encaminhadas ao desenvolvedor do software para adequação e ajustes, e posteriormente submetidas à segunda rodada. Oito especialistas participaram da segunda rodada. Foram obtidos índices de 80% e 90% de concordância entre os juízes, caracterizando uniformidade nas sugestões. Dessa forma, houve modificação no layout do software para adequação linguística e cultural, minimizando erros de entendimento e contradições. Na segunda etapa, foram incluídos 21 pacientes, e não houve diferenças entre doses de piperacilina nos grupos dose padronizada e dose ajustada. Conclusão A versão adaptada do software é segura e confiável para seu uso no Brasil.

Piperacillin/tazobactam plus amikacin vs. piperacilin/tazobactam: treatment for children with febrile neutropenia / Piperacilina/tazobactam más amikacina vs. piperacilina/tazobactam: tratamiento en niños con neutropenia febril

Background: Pediatric patients with febrile neutropenia usually receive a combination of broad spectrum antimicrobials. Treatment without aminoglycoside seems to have advantages. Objective: To compare the efficacy of piperacillin/tazobactam plus amikacin versus piperacillin/tazobactam. Methods: Randomized, open label, controlled clinical trial. Sample size for an efficacy of 55%, and delta of 25%; 80 episodes were required for each group. Selection criteria were patients with febrile neutropenia, candidates to receive parenteral antimicrobial treatment; they were randomized to one of two groups, piperacillin/tazobactam plus amikacin (Group A), or piperacillin/tazobactam (Group B). The outcomes were failure, adverse events and death. Mantel-Haenszel chi squaretest and exact Fisher test were used. Reduction of relative and absolute risk (RRR and ARR), 95% confidence intervals (CI 95%) and number needed to treat (NNT) were calculated. Results: 88 Episodes were analyzed in group A and 76 in group B. There was no statistical difference in general characteristics of patients or type of infections. There was not significant statistical difference in: failure 31.8% group A, 30.2% group B (RR 1.05, CI 95% 0.66-1.66, p = 0.86), or adverse events (one in each group). The RRR was 1.5%, and ARR 2%, with a NNT of 67. Conclusion: Piperacillin/tazobactam without amikacin was as effective as combination therapy in pediatric patients with febrile neutropenia.

Introducción: los pacientes pediátricos con neutropenia febril habitualmente reciben una combinación de antimicrobianos de amplio espectro. La terapia sin aminoglucósido parece tener ventajas. Objetivo: comparar la eficacia de piperacilina/tazobactam más amikacina frente a la de piperacilina/tazobactam. Métodos: ensayo clínico controlado aleatorizado. Tamaño de muestra para una eficacia de 55%, y delta de 25%; se calcularon 80 episodios por grupo. Fueron seleccionados pacientes con neutropenia febril, candidatos a recibir antimicrobiano parenteral; se aleatorizaron a recibir piperacilina/tazobactam más amikacina (grupo A) o piperacilina/tazobactam (grupo B). Los desenlaces fueron falla, eventos adversos y muerte. Se emplearon las pruebas Chi cuadrada de Mantel-Haenszel y exacta de Fisher. Se calculó la reducción de riesgo relativo y absoluto (RRR y RRA), intervalos de confianza 95% (IC 95%) y número necesario a tratar (NNT). Resultados: se analizaron 88 episodios en el grupo A y 76 en el grupo B. No hubo diferencias estadísticas en características generales ni en el tipo de infecciones. No se encontró diferencia significativa en: falla 31.8% grupo A, 30.2% grupo B (RR 1.05, IC 95% 0.66-1.66, p = 0.86), ni en los eventos adversos (uno en cada grupo). La RRR fue de 1.5%, RRA de 2%, con un NNT de 67. Conclusión: la terapia con piperacilina/tazobactam sin amikacina fue tan efectiva como la terapia combinada para pacientes pediátricos con neutropenia febril.

Delftia acidovorans pneumonia with lung cavities formation / Neumonia con formación de cavidades pulmonares causada por Delftia acidovorans

Abstract Case Description: A 52-year-old female patient was admitted to our clinic with complaints of cough, sputum, fever and fatigue. The patient has been receiving immunosuppressive therapy for thrombocytopenic purpura for 5 years. Clinical Finding: Inspiratory crackles were heard on both hemithorax. Oxygen saturation measured with the pulse oximeter was 97%. Chest X-ray showed diffuse reticular opacities that were more prominent in the upper zones of both lungs. WBC counts were 17,600 mm3 and Platelet counts were 29,000 mm3. Thorax CT showed that there were many thin-walled cavities and millimetric nodules accompanied by ground-glass infiltrates in the upper and middle lobes. Gram staining of bronchial fluid, taken by bronchoscopy, revealed Gram-negative bacilli and intense polymorphonuclear leukocytes. The bacteria were defined as Delftia acidovorans by BD Phoenix automated system. Treatment and outcomes: The patient was hospitalized with suspicion of opportunistic pulmonary infections and cavitary lung disease. After the empirical treatment of intravenous piperacillin-tazobactam and oral clarithromycin, her clinical and radiological findings significantly regressed, and she was discharged with outpatient follow-up. Clinical Relevance: This is the first example of cavitary pneumonia due to Delftia acidovorans in an immunocompromised patient. We would like to emphasize that Delftia pneumonia should be considered in the differential diagnosis of pulmonary cavitary involvement in such patients.

Resumen Descripción del caso: Una mujer de 52 años llegó a la clínica con tos, esputo, fiebre y fatiga. El paciente estuvo recibiendo terapia inmunosupresora durante 5 años para el tratamiento de la púrpura trombocitopénica. Hallazgo clínico: se escucharon crepitaciones inspiratorias en ambos hemitórax. La saturación de oxígeno fue del 97%. La radiografía de tórax mostró opacidades reticulares difusas que eran más prominentes en las zonas superiores de ambos pulmones. Los recuentos de leucocitos fueron de 17,600 mm3 y los recuentos de plaquetas fueron de 29,000 mm3. La TC de tórax mostró muchas cavidades de pared delgada y nódulos milimétricos acompañados de infiltrados vitrales en los lóbulos superior y medio. La tinción de Gram del líquido bronquial reveló bacilos gramnegativos y leucocitos polimorfonucleares. Las bacterias fueron identificadas como Delftia acidovorans. Tratamiento y resultados: La paciente fue hospitalizado con una sospecha de infección oportunista pulmonar y enfermedad pulmonar cavitaria. Después del tratamiento empírico de piperacilina-tazobactam intravenosa y claritromicina oral, los síntomas y signos retrocedieron significativamente, y fue dada de alta con seguimiento ambulatorio. Relevancia clínica: este es el primer registro de neumonía cavitaria causado por Delftia acidovorans en una paciente inmunocomprometida. Enfatizamos que la neumonía por Delftia debe considerarse en el diagnóstico diferencial de la afectación de la cavidad pulmonar en tales pacientes.

PIPERACILLIN/TAZOBACTAM IN CONTINUOUS INFUSION VERSUS INTERMITTENT INFUSION IN CHILDREN WITH FEBRILE NEUTROPENIA.

Background: Febrile neutropenia (FN) is a common complication in children who receive chemotherapy for cancer. Objective: The objective of this study was to evaluate the clinical efficacy of the continuous versus intermittent infusion of piperacillin/tazobactam (TZP) in febrile neutropenic pediatric patients. Methods: This is a non-blinded randomized controlled clinical trial. Eligible group consisted of hemato-oncological patients with FN who were candidates to receive TZP. Patients were randomized to one of two groups: Group 1 received antibiotic treatment through intravenous intermittent infusion of TZP 300 mg/kg/day based on piperacillin, divided into four doses, not exceeding 16 g/day; Group 2 received an initial TZP loading dose of 75 mg/kg infusion over 30 min, and then a continuous infusion of TZP 300 mg/kg/day through central line with pump over 24 h. Results: There were 176 episodes that could be assessed, 100 in Group 1 and 76 in Group 2. There was no statistically significant difference in treatment failure in the experimental group (continuous infusion) compared with the intermittent group, 21% versus 13% (p = 0.15). The increase in the absolute risk reduction was 0.08% (95% confidence interval 0.12-0.30), and the number needed to treat was 12.4. One patient in each group died. Conclusions: There were no differences in fever resolution, clinical cure rate, or mortality when comparing the continuous with the intermittent TZP infusion.

Piperacillin/tazobactam in continuous infusion versus intermittent infusion in children with febrile neutropenia

Abstract Background Febrile neutropenia (FN) is a common complication in children who receive chemotherapy for cancer. Objective The objective of this study was to evaluate the clinical efficacy of the continuous versus intermittent infusion of piperacillin/tazobactam (TZP) in febrile neutropenic pediatric patients. Methods This is a non-blinded randomized controlled clinical trial. Eligible group consisted of hemato-oncological patients with FN who were candidates to receive TZP. Patients were randomized to one of two groups: Group 1 received antibiotic treatment through intravenous intermittent infusion of TZP 300 mg/kg/day based on piperacillin, divided into four doses, not exceeding 16 g/day; Group 2 received an initial TZP loading dose of 75 mg/kg infusion over 30 min, and then a continuous infusion of TZP 300 mg/kg/day through central line with pump over 24 h. Results There were 176 episodes that could be assessed, 100 in Group 1 and 76 in Group 2. There was no statistically significant difference in treatment failure in the experimental group (continuous infusion) compared with the intermittent group, 21% versus 13% (p = 0.15). The increase in the absolute risk reduction was 0.08% (95% confidence interval 0.12-0.30), and the number needed to treat was 12.4. One patient in each group died. Conclusions There were no differences in fever resolution, clinical cure rate, or mortality when comparing the continuous with the intermittent TZP infusion.

Delftia acidovorans pneumonia with lung cavities formation.

CASE DESCRIPTION: A 52-year-old female patient was admitted to our clinic with complaints of cough, sputum, fever and fatigue. The patient has been receiving immunosuppressive therapy for thrombocytopenic purpura for 5 years. CLINICAL FINDING: Inspiratory crackles were heard on both hemithorax. Oxygen saturation measured with the pulse oximeter was 97%. Chest X-ray showed diffuse reticular opacities that were more prominent in the upper zones of both lungs. WBC counts were 17,600 mm3 and Platelet counts were 29,000 mm3. Thorax CT showed that there were many thin-walled cavities and millimetric nodules accompanied by ground-glass infiltrates in the upper and middle lobes. Gram staining of bronchial fluid, taken by bronchoscopy, revealed Gram-negative bacilli and intense polymorphonuclear leukocytes. The bacteria were defined as Delftia acidovorans by BD Phoenix automated system. TREATMENT AND OUTCOMES: The patient was hospitalized with suspicion of opportunistic pulmonary infections and cavitary lung disease. After the empirical treatment of intravenous piperacillin-tazobactam and oral clarithromycin, her clinical and radiological findings significantly regressed, and she was discharged with outpatient follow-up. CLINICAL RELEVANCE: This is the first example of cavitary pneumonia due to Delftia acidovorans in an immunocompromised patient. We would like to emphasize that Delftia pneumonia should be considered in the differential diagnosis of pulmonary cavitary involvement in such patients.

DESCRIPCIÓN DEL CASO: Una mujer de 52 años llegó a la clínica con tos, esputo, fiebre y fatiga. El paciente estuvo recibiendo terapia inmunosupresora durante 5 años para el tratamiento de la púrpura trombocitopénica. HALLAZGO CLÍNICO: se escucharon crepitaciones inspiratorias en ambos hemitórax. La saturación de oxígeno fue del 97%. La radiografía de tórax mostró opacidades reticulares difusas que eran más prominentes en las zonas superiores de ambos pulmones. Los recuentos de leucocitos fueron de 17,600 mm3 y los recuentos de plaquetas fueron de 29,000 mm3. La TC de tórax mostró muchas cavidades de pared delgada y nódulos milimétricos acompañados de infiltrados vitrales en los lóbulos superior y medio. La tinción de Gram del líquido bronquial reveló bacilos gramnegativos y leucocitos polimorfonucleares. Las bacterias fueron identificadas como Delftia acidovorans. TRATAMIENTO Y RESULTADOS: La paciente fue hospitalizado con una sospecha de infección oportunista pulmonar y enfermedad pulmonar cavitaria. Después del tratamiento empírico de piperacilina-tazobactam intravenosa y claritromicina oral, los síntomas y signos retrocedieron significativamente, y fue dada de alta con seguimiento ambulatorio. RELEVANCIA CLÍNICA: este es el primer registro de neumonía cavitaria causado por Delftia acidovorans en una paciente inmunocomprometida. Enfatizamos que la neumonía por Delftia debe considerarse en el diagnóstico diferencial de la afectación de la cavidad pulmonar en tales pacientes.

Evaluación de susceptibilidad y respuesta al tratamiento con piperacilina/tazobactam en pacientes con infecciones por Escherichia coli productoras de β -lactamasas de espectro extendido (BLEE) CTX-M / Evaluation of susceptibility and response to therapy with piperacillin-tazobactam in patients with infections caused by Escherichia coli with extended-spectrum β -lactamase (ESBL) CTX-M

Resumen Introducción: En las infecciones por enterobacterias productoras de β-lactamasas de espectro extendido (BLEE), los β-lactámicos preferidos para tratamiento son los carbapenémicos. Sin embargo, estudios clínicos muestran eficacia de piperacilina/tazobactam en ciertas infecciones por Escherichia coli productoras de BLEE. Objetivo: Determinar la cura clínica y microbiológica con piperacilina/tazobactam en pacientes con infecciones por E. coli productoras de BLEE, tipo CTX-M. Materiales/Métodos: Estudio descriptivo, retrospectivo, con adultos internados en un hospital universitario. Incluimos infecciones del tracto urinario (ITU), intra-abdominales (IIA) e infecciones de tejidos blandos (ITB). Resultados: Estudiamos 40 pacientes, donde 65% correspondían a ITU, 25% IIA y 10 % ITB. La cura clínica global se logró en 89,4%, con mejores resultados en las ITU (100%), seguidas de ITB (80%) e IIA (70%). El 85% de las cepas tenía concentraciones inhibitorias mínimas (CIM) ≤ 8 μg/mL y 70% con CIM ≤ 4 μg/mL. La tasa de fracaso fue mayor en las infecciones con inóculos altos intraabdominales. La BLEE del tipo CTX-M-15 se encontró en 62,5%. Conclusiones: Piperacilina/tazobactam logró cura clínica y microbiológica, en pacientes con infecciones por E. coli productoras de BLEE susceptibles, especialmente en ITU e IPB y en menor medida en IIA.

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

Susceptibilidad de enterobacterias a piperacilina/tazobactam en un hospital pediátrico de Chile / Enterobacteriaceae susceptibility to piperacillin/tazobactam in a Chilean pediatric hospital

Resumen Introducción: Las enterobacterias son bacilos gram-negativos responsables de infecciones graves en el ser humano. Se reporta una susceptibilidad en Klebsiella pneumoniae de 79,4% a piperacilina/tazobactam (PIP/TAZO) en hospitales pediátricos de Chile, pero según nuestro conocimiento, no existen datos publicados a la fecha respecto a la susceptibilidad de otras enterobacterias a PIP/TAZO en la población pediátrica chilena. Objetivo: Determinar la susceptibilidad in vitro a PIP/TAZO en cepas obtenidas de infecciones por Enterobacteriaceae en un hospital pediátrico de Chile. Material y Método: Estudio descriptivo y prospectivo de cepas de Enterobacteriaceae en Hospital de Niños Roberto del Río (HRRIO) entre 1 de enero de 2013 y el 27 de agosto de 2014. Se definió la susceptibilidad a PIP/TAZO por método de gradiente (E-test®) según puntos de corte CLSI 2014. Resultados: Se incluyeron 163 casos. El promedio de edad fue de 4 años 15 días. 70,6% de sexo femenino. El 79,7% de las cepas fueron aisladas en urocultivos. La susceptibilidad de Enterobacteriaceae a PIP/TAZO fue 95,1% (n = 155). La susceptibilidad intermedia fue 1,8% (n = 3). Discusión: Los aislados estudiados presentan alta susceptibilidad a PIP/TAZO. Este hallazgo puede explicarse por la baja circulación de microrganismos productores de BLEE y el limitado uso de PIP/TAZO en esta población pediátrica.

Introduction: Enterobacteriaceae are a group of gram-negative rods that can cause serious infections in humans. A susceptibility in Klebsiella pneumoniae of 79.4% to piperacillin/tazobactam (PIP/TAZO) is reported in pediatric hospitals in Chile. There is no published data published to date regarding PIP/TAZO susceptibility to other Enterobacteriaceae species in this population. Aim: To measure the in vitro PIP/TAZO susceptibility in Enterobacteriaceae isolates from patients in a pediatric hospital in Chile. Methods: Descriptive and prospective study of Enterobacteriaceae positive cultures from patients assisting to the "Hospital de niños Roberto del Río" (HRRIO) between January 2013 and August 2014. PIP/TAZO susceptibility was established by gradient diffusion method (E-test®) according to the 2014 CLSI standards. Results: 163 cases were included. The average age was 4 years and 15 days. 70.6% were female. 79.7% of samples were urine cultures. PIP/TAZO susceptibility in Enterobacteriaceae was 95.1% (n = 155). The intermediate susceptibility was 1.8% (n = 3). Discussion: The isolates studied present high susceptibility to PIP/TAZO. This finding could be explained by the fact that this population has not been exposed to this antimicrobial therapy and also the low rates for ESBL in pediatric infections.

In vivo pharmacodynamics of piperacillin/tazobactam: implications for antimicrobial efficacy and resistance suppression with innovator and generic products.

Recent studies have shown that the pharmacodynamic (PD) index driving the efficacy of ß-lactam/ß-lactamase inhibitor combinations such as ceftazidime/avibactam and ceftolozane/tazobactam is the percentage of time the free inhibitor concentration is above a threshold (fT>threshold). However, data with piperacillin/tazobactam (TZP) are scarce. Here we aimed to assess the relationship between fT>threshold and TZP antibacterial efficacy by a population pharmacokinetic study in mice and dose-effect experiments in a neutropenic murine thigh infection model with two isogenic strains of Escherichia coli differentially expressing TEM-1 ß-lactamase. We also explored the dynamics of resistance selection with the innovator and a non-equivalent generic, extrapolated the results to the clinic by Monte Carlo simulation of standard TZP doses, and estimated the economic impact of generic-selected resistance. The fT>threshold index described well the efficacy of TZP versus E. coli, with threshold values from 0.5 mg/L to 2 mg/L and mean exposures of 42% for stasis and 56% for 1 log10 kill. The non-equivalent generic required a longer exposure (fT>threshold 33%) to suppress resistance compared with the innovator (fT>threshold 22%), leading to a higher frequency of resistance selection in the clinical simulation (16% of patients with the generic vs. 1% with the innovator). Finally, we estimated that use of TZP generics in a scenario of 25% therapeutic non-equivalence would result in extra expenses approaching US$1 billion per year in the USA owing to selection of resistant micro-organisms, greatly offsetting the savings gained from generic substitution and further emphasising the need for demonstrated and not assumed therapeutic equivalence.

A meta-analysis of piperacillin/tazobactam versus cefepime treatment in cancer patients with febrile neutropenia / Uma meta análise de piperacilina/tazobactam versus tratamento com cefepima em pacientes oncológicos com neutropenia febril

Febrile neutropenia (FN) causes a major threat to cancer patients after chemotherapy. Broadspectrum antibiotic treatment is a well-established practice for febrile neutropenia. Piperacillin/Tazobactam (P/T) is the frequently used antibiotic in most of FN cases, whereas the use of cefepime remains unclear regarding its potential risk. However, little systematic analysis has been conducted about comparison between these two drugs. Thus, we undertook this meta-analysis to compare these two monotherapies for febrile neutropenia. Through searching Pubmed, Google scholar, Medline databases, EMBASE, OvidSP, ScienceDirect, Web of science, and China Journal Net (CJN) databases, we used the keywords "(Piperacillin/Tazobactam AND cefepime) AND (febrile neutropenia) AND (cancer or tumor)". Only studies with randomized controlled trials were included in the meta-analysis. We screened out a total number of seven clinical trials. This meta-analysis supported that P/T treatment was superior to cefepime treatment based on the average OR comparison, without statistical significance (OR = 1.27, 95% confidence interval = 0.98 to 1.64, p = 0.07). We further divided the seven studies into two subgroups based on age and treatment time. The young group (age <= 19) showed no significant difference (OR = 1.10, p = 0.65). While the old group (age > 19) showed that P/T treatment was better than cefepime with statistical difference (OR = 1.44, p = 0.05). The short-term group (time <= 3 ds) showed P/T treatment was better than cefepime with statistical difference (OR = 1.40, p = 0.05). While in the long-term group (time > 5 ds), there was no significant difference between P/T and cefepime therapy (OR = 1.06, p = 0.79) Asymmetry in Funnel plots indicated no publication bias (CHI2 = 1.47, I2=0%, and p-value = 0.96) in this meta-analysis. It would be a good clinical trial to use P/T treatment to cure FN in cancer patients compared with cefepime treatment, especially in adult patients or patients with a short-term treatment period. This meta-analysis is practically important during antibiotic treatment in FN management.

A Neutropenia Febril (NF) apresenta-se como uma grande ameaça aos pacientes oncológicos após a quimioterapia. O tratamento antibiótico de amplo espectro é uma prática bem estabelecida para a neutropenia febril. Piperacilina/tazobactam (P/T) é o antibiótico frequentemente na maioria dos casos de NF, enquanto que o uso de cefepima permanece pouco claro em relação ao seu potencial risco. No entanto, pouca análise sistemática foi feita sobre a comparação entre esses dois fármacos. Assim, nós realizamos esta meta-análise para comparar estas duas monoterapias para a neutropenia febril. Através da pesquisa na Pubmed, Google Scholar, nas bases de dados da Medline, EMBASE, OvidSP, ScienceDirect, Web of science e nas bases de dados do China Journal Net (CJN), nós usamos as palavras-chave "(Piperacillin/Tazobactam AND cefepime) AND (febrile neutropenia) AND (cancer or tumor)". Apenas estudos com ensaios clínicos randomizados foram incluídos na meta-análise. Nós selecionamos um número total de sete ensaios clínicos. Esta meta-análise suportou que o tratamento com P/T foi superior ao tratamento com cefepima baseado na média da comparação OU (average OR comparision, em inglês), sem significância estatística (OR = 1.27, 95% confidence interval = 0.98 to 1.64, p = 0.07). Posteriormente, nós dividimos os sete estudos em dois subgrupos baseados na idade e no tempo de tratamento. O grupo jovem (idade <= 19) não mostrou uma diferença significativa (OR = 1.10, p = 0.65). Enquanto que o grupo mais velho (idade > 19) mostrou que o tratamento com P/T foi melhor do que o com cefepima com diferença estatística (OR = 1.44, p = 0.05). O grupo de curto prazo (tempo <= 3 ds*) mostrou que o tratamento com P/T foi melhor do que o com cefepima com diferença estatística (OR = 1.40, p = 0.05). Enquanto isso, no grupo de longo termo (tempo > 5 ds) não houve diferença significativa entre as terapias com P/T e Cefepima (OR = 1.06, p = 0.79). A assimetria nos gráficos de funil (funnel plots, em inglês) não indicaram viés de publicação (CHI2 = 1.47, I2=0%, and pvalue = 0.96) nesta meta-análise. Seria um bom ensaio clínico utilizar o tratamento P/T para curar NF em pacientes oncológicos comparados com o tratamento com cefepima, especialmente em pacientes adultos ou pacientes submetidos a um tratamento de curto prazo. Esta meta-análise é importante na prática durante o tratamento com antibióticos na administração de NF.

Impact of piperacillin-tazobactam shortage on meropenem use: implications for antimicrobial stewardship programs.

Drug shortages pose a clear detriment to antimicrobial stewardship (AS) efforts. Our objective was to evaluate the effect of a piperacillin-tazobactam shortage on meropenem use, related costs, and associated changes in AS activity. A quasi-experimental quality improvement review compared adult patients receiving meropenem ≥72h three months pre-shortage and three months during the shortage. 320 patients were included (pre-shortage: 103; shortage: 217). Baseline characteristics were similar, but the length of stay was slightly longer in pre-shortage [19 (11-32) days] versus shortage [16 (11-32) days] (p=0.094). In pre-shortage and shortage, median days of therapy and estimated meropenem cost were 7 (5-11) and 7 (5-10) and $309.93 ($173.60-$507.03) and $255.30 ($204.24-$424.31), respectively (p=0.411 and p=0.050). Frequency of ID consultation was similar (16.8% in pre- and 25.3% in shortage, p=0.091). AS interventions increased during the shortage period (99 in pre-shortage and 205 in shortage). De-escalation occurred in 19.4% versus 32.7% of the patients in pre-shortage and shortage (p=0.014). The piperacillin-tazobactam shortage was associated with a 111% increase in meropenem prescriptions despite active AS, but was not associated with changes in mortality, length of therapy, or meropenem costs. AS should be aware that shortages may require proactive countermeasures to avoid inappropriate antimicrobial use during shortage periods.