Multicenter study on the efficacy and safety of 3 kinds of Cephalosporin for injection from centralized procurement or non-centralized procurement / 中国药房

OBJECTIVE To compare the efficacy and safety of Cefazolin sodium for injection， Cefuroxime sodium for injection， and Ceftazidime for injection from nationally organized centralized drug procurement （hereinafter referred to as “centralized procurement”） and non-centralized procurement in patients with bacterial infection. METHODS The case data of hospitalized patients who had used 3 kinds of Cephalosporins for injection from centralized procurement or non-centralized procurement in the treatment of bacterial infections were retrospectively collected from 19 medical institutions in Kunming from January 2020 to September 2022. After balancing the baseline differences between the groups with the propensity score matching method， the effectiveness and safety differences of 3 kinds of Cephalosporins for injection from centralized procurement or non- centralized procurement were compared respectively. RESULTS After balancing the baseline differences among the groups， 394 cases in each group of Cefazolin sodium for injection from centralized procurement or non-centralized procurement， 472 cases in each group of Cefuroxime sodium for injection from centralized procurement or non-centralized procurement， 504 cases in group of Ceftazidime for injection from centralized procurement and 590 cases in group of non-centralized procurement were included in the analysis. In terms of effectiveness， there were no significant differences in clinical response rate， 72 h response rate， bacterial clearance rate， and the recovery rate of body temperature， white blood cell count， neutrophil count， neutrophil percentage， C-reactive protein， procalcitonin recovery between the centralized procurement group and non-centralized procurement group of Cefazolin sodium for injection and Cefuroxime sodium for injection （P＞0.05）. The proportion of patients in centralized procurement group of Ceftazidime for injection with C-reactive protein restored to normal reference range was significantly higher than that in non-centralized procurement group （46.9% vs. 27.9%， P＜0.05）， but there were no statistically significant differences in other effectiveness indicators among groups （P＞0.05）. In terms of safety， there was no statistical difference in the incidence of adverse drug reactions between centralized procurement group and non-centralized procurement group of 3 kinds of Cephalosporins for injection （P＞0.05）； the incidence of platelet count reduction in centralized procurement group of Cefazolin sodium for injection was significantly higher than non-centralized procurement group （20.7% vs. 7.1%， P＜0.05）， the incidence of eosinophilia elevation in centralized procurement group of Ceftazidime for injection was significantly higher than non-centralized procurement group （5.3% vs. 1.9%， P＜0.05）. In addition， there was no statistically significant difference in the abnormal rates of other laboratory indicators among the three types of injection Cephalosporins （P＞ 0.05）. CONCLUSIONS The efficacy of 3 kinds of Cephalosporin for injection from centralized procurement is not inferior to non- centralized procurement varieties， and the safety is equivalent to that of non-centralized procurement varieties.

Ceftazidima/avibactam frente a otros antimicrobianos para el tratamiento de bacteriemias por Enterobacterales productores de carbapenemasa KPC: datos de la vida real en un hospital universitario de Argentina

Introducción: Las bacteriemias por Enterobacterales productores de carbapenemasa KPC (EPC-KPC) presentan una mortalidad elevada y opciones terapéuticas limitadas. Objetivos: Describir y comparar la evolución de los pacientes con bacteriemia por EPC-KPC tratados con ceftazidima/avibactam (CA) frente a otros antimicrobianos (OA). Pacientes y Métodos: Estudio prospectivo y retrospectivo de casos y controles. Se incluyeron pacientes adultos con bacteriemia por EPC-KPC, con una proporción entre casos tratados con CA y controles tratados con OA. de 1:2. Se analizaron variables clínicas, epidemiológicas y de evolución. Resultados: Se incluyeron 48 pacientes (16 CA y 32 OA). Los casos se encontraban más frecuentemente neutropénicos (50 vs.16%, p = 0,012); asimismo, presentaron medianas de score de APACHE II más altas y de score de Pitt más bajas. El 65% de la cohorte total presentó un foco clínico y Klebsiellapneumoniae fue el microorganismo más frecuentemente aislado. Los casos recibieron una mayor proporción de tratamiento antimicrobiano empírico adecuado (81 vs. 53%, p = 0,05). La antibioterapia dirigida en casos y controles fue combinada en 38 y 91%, p = 0,009. Los casos presentaron menor mortalidad al día 7 y al día 30 relacionada a infección (0 vs. 22%, p = 0,04 y 0 vs. 34%, p = 0,008). Solo los controles desarrollaron shock, ingresaron a la unidad de cuidados intensivos y presentaron bacteriemia de brecha. Conclusión: CA mostró beneficio clínico frente a OA para el tratamiento de pacientes con bacteriemia por EPC-KPC.

Background: KPC-producing Enterobacterales bacteremia (KPCCPE) is associated with a high mortality rate and limited therapeutic options. Aim: To describe and compare the outcome of patients with KPC-CPE bacteremia treated with ceftazidime/avibactam (CA) versus other antibiotics (OA). Methods: Prospective and retrospective cases and control study performed in adult patients with KPC-CPE bacteremia, with a 1:2 ratio between cases treated with CA. and controls treated with OA. Clinical, epidemiological, and outcome variables were analyzed. Results: Forty-eight patients (16 CA and 32 OA) were included. Cases were more frequently neutropenic (50 vs. 16%, p = 0.012), presented higher median APACHE II score and lower Pitt score. Of the total cohort, 65% had a clinical source, and Klebsiella pneumoniae was the most frequently isolated microorganism. Cases received more adequate empirical antibiotic treatment (81 vs. 53%, p = 0.05). Targeted antibiotic therapy in cases and controls was combined in 38 and 91%, p = 0.009. Cases had a lower 7-day mortality and 30-day infection-related mortality (0 vs. 22%, p = 0.04 and 0 vs. 34%, p = 0.008). Only controls developed shock, were admitted to the intensive care unit, and had breakthrough bacteremia. Conclusion: CA. showed clinical benefit over OA in the treatment of patients with EPC-KPC bacteremia.

Uso de ceftazidima-avibactam en una recién nacida prematura con infección urinaria bacteriémica por Klebsiella pneumoniae productora de carbapenemasa

Los recién nacidos tienen un alto riesgo de morbimortalidad asociada a infecciones durante su estancia en unidades de cuidado intensivo neonatal, a lo que se asocia un aumento progresivo de infecciones por microorganismos multi-resistentes que requiere el uso de nuevos antimicrobianos. Presentamos el caso de una recién nacida de pretérmino de 36 semanas que cursó con una infección del tracto urinario bacteriémica por Klebsiella pneumoniae productora de carbapenemasa tratada de forma efectiva con 14 días de cefazi- dima-avibactam, sin efectos adversos observados. Según nuestro conocimiento, este es el primer caso reportado en nuestro país del uso de este antimicrobiano en población neonatal. Se necesita más información sobre la eficacia y seguridad de ceftazidima-avibactam en este grupo de pacientes.

Neonates are high risk patients regarding morbimortality secondary to infections during their neonatal intensive care unit stay, which is associated to a progressive increase in the report of multidrug resistant organism infections, that require the use of new antimicrobial. We report the case of a 36-week preterm with an urinary tract infection with bacteriemia caused by carbapenemase- producing Klebsiella pneumoniae treated effectively with 14 day of ceftazidime-avibactam, without observed adverse effects. To our knowledge, this is the first case report in our country of the use of this antibiotic in neonatal population. More information is needed regarding efficacy and safety of ceftazidime-avibactam in this group of patients.

Epidemiology and in vitro activity of ceftazidime-avibactam and comparator agents against multidrug-resistant isolates of Enterobacterales and Pseudomonas aeruginosa collected in Latin America as part of the ATLAS surveillance program in 2015‒2020

Abstract Introduction The incidence of antimicrobial resistance is increasing in many parts of the world. The focus of this report is to examine changes in antimicrobial resistance epidemiology among clinical isolates of Enterobacterales and Pseudomonas aeruginosa collected in six Latin American countries as part of the Antimicrobial Testing Leadership and Surveillance (ATLAS) program from 2015 to 2020, with a focus on the in vitro activity of ceftazidime-avibactam against Multidrug-Resistant (MDR) isolates. Methods Non-duplicate, clinical isolates of Enterobacterales (n= 15,215) and P. aeruginosa (n= 4,614) collected by 40 laboratories in Argentina, Brazil, Chile, Colombia, Mexico, and Venezuela, from 2015 to 2020, underwent centralized Clinical Lab Standards Institute (CLSI) broth microdilution susceptibility testing. Minimum Inhibitory Concentration (MIC) values were interpreted using 2022 CLSI breakpoints. An MDR phenotype was defined by resistance to ≥ 3 of seven sentinel agents. Results In total, 23.3% of Enterobacterales and 25.1% of P. aeruginosa isolates were MDR. Annual percent MDR values for Enterobacterales were stable from 2015 to 2018 (21.3% to 23.7% year) but markedly increased in 2019 (31.5%) and 2020 (32.4%). Annual percent MDR values for P. aeruginosa were stable from 2015 to 2020 (23.0% to 27.6% year). Isolates were divided into two 3-year time-periods, 2015‒2017 and 2018‒2020, for additional analyses. For Enterobacterales, 99.3% of all isolates and 97.1% of MDR isolates from 2015‒2017 were ceftazidime-avibactam-susceptible compared to 97.2% and 89.3% of isolates, respectively, from 2018‒2020. For P. aeruginosa, 86.6% of all isolates and 53.9% of MDR isolates from 2015‒2017 were ceftazidime-avibactam-susceptible compared to 85.3% and 45.3% of isolates, respectively, from 2018‒2020. Among individual countries, Enterobacterales and P. aeruginosa collected in Venezuela showed the greatest reductions in ceftazidime-avibactam susceptibility over time. Conclusion MDR Enterobacterales increased in Latin America from 22% in 2015 to 32% in 2020 while MDR P. aeruginosa remained constant at 25%. Ceftazidime-avibactam remains highly active against all clinical isolates of both Enterobacterales (97.2% susceptible, 2018‒2020) and P. aeruginosa (85.3%), and inhibited more MDR isolates (Enterobacterales, 89.3% susceptible, 2018‒2020; P. aeruginosa, 45.3%) than carbapenems, fluoroquinolones, and aminoglycosides.

Evaluation of in-vitro susceptibility of ß-lactam-resistant Gram-negative bacilli to ceftazidime-avibactam and ceftolozane-tazobactam from clinical samples of a general hospital in southern Brazil

ABSTRACT Background: The spread of carbapenemase- and extended-spectrum β-lactamase (ESBL)-producing gram-negative bacilli (GNB) represent a global public health threat that limits therapeutic options for hospitalized patients. This study aimed to evaluate the in-vitro susceptibility of β-lactam-resistant GNB to ceftazidime-avibactam (C/A) and ceftolozane-tazobactam (C/T), and investigate the molecular determinants of resistance. Methods: Overall, 101 clinical isolates of Enterobacterales and Pseudomonas aeruginosa collected from a general hospital in Brazil were analyzed. Susceptibility to the antimicrobial agents was evaluated using an automated method, and the minimum inhibitory concentrations (MIC50/90) of C/A and C/T were determined using Etest®. The β-lactamase-encoding genes were investigated using polymerase chain reaction. Results: High susceptibility to C/A and C/T was observed among ESBL-producing Enterobacterales (100% and 97.3% for CLSI and 83.8% for BRCAST, respectively) and carbapenem-resistant P. aeruginosa (92.3% and 87.2%, respectively). Carbapenemase-producing Klebsiella pneumoniae exhibited high resistance to C/T (80%- CLSI or 100%- BRCAST) but high susceptibility to C/A (93.4%). All carbapenem-resistant K. pneumoniae isolates were susceptible to C/A, whereas only one isolate was susceptible to C/T. Both antimicrobials were inactive against metallo-β-lactamase-producing K. pneumoniae isolates. Resistance genes were concomitantly identified in 44 (44.9%) isolates, with bla CTX-M and bla SHV being the most common. Conclusions: C/A and C/T were active against microorganisms with β-lactam-resistant phenotypes, except when resistance was mediated by metallo-β-lactamases. Most C/A- and C/T-resistant isolates concomitantly carried two or more β-lactamase-encoding genes (62.5% and 77.4%, respectively).

Efficacy and safety of ceftazidime and avibactam sodium in the treatment of carbapenem-resistant organism infection / 中国药房

OBJECTIVE To observe the efficacy and safety of ceftazidime and avibactam sodium （CAZ/AVI） in the treatment of carbapenem-resistant organism （CRO） infection. METHODS The information of patients with CRO infection admitted to the Second Affiliated Hospital of Soochow University from September 2019 to March 2022 was collected， and the patients were retrospectively divided into observation group （48 cases） and control group （48 cases） according to the treatment plan. The control group was given Polycolistin B sulfate for injection intravenously at a dose of 500 000 U every 12 hours； no dose adjustment was performed in patients with renal insufficiency or receiving continuous renal replacement therapy （CRRT）. The observation group was given continuous micropump of CAZ/AVI for injection intravenously at a dose of 2.5 g every 8 hours for 2 continous hours； among them， the patients with renal insufficiency received an adjusted dose based on creatinine clearance， and no dose adjustment was performed in patients receiving CRRT. The clinical efficacy and microbiological efficacy as well as body temperature， white blood cell （WBC）， C-reactive protein （CRP） and procalcitonin （PCT） before and after treatment were compared between 2 groups. The prognosis and the occurrence of adverse drug reactions were recorded. The factors influencing the clinical efficacy were screened by Logistic regression analysis. RESULTS The effective rate and microbial clearance rate of the observation group were significantly higher than the control group （P＜0.05）. After treatment， body temperature， PCT and CRP of 2 groups were significantly lower than before treatment， and CRP of the observation group was significantly lower than the control （No.SDFEYJLC2105） group （P＜0.05）. There was no statistically significant differencebetween the two groups in terms of rehabilitation discharge rate， the proportion of patients transferred to general wards，the proportion of dead patients， and the total incidence ofadverse drug reactions （P＞0.05）. CAZ/AVI and prolonging therapy duration were more likely to achieve clinical benefits （odds ratios of 1.146， 7.707，P＜0.05）， while lung infection and CRRT may be independent risk factors for treatment failure （odds ratios of 0.182， 0.236， P＜0.05）. CONCLUSIONS CAZ/AVI has good efficacy and safety in the treatment of CRO infection， the appropriate extension of antibacterial treatment time can achieve a higher clinical response rate， while lung infection or CRRT may lead to treatment failure.

Real-world study of ceftazidime-avibactam in the treatment of multidrug-resistant gram-negative bacterial infections / 中国临床药理学与治疗学

AIM: To describe and evaluate the clinical characteristics, treatment management and clinical outcomes of ceftazidime-avibactam (CZA) in the treatment of patients with multidrug-resistant gram-negative bacterial (MDR-GNB) infections. METHODS: A retrospective cohort study was performed on patients hospitalized in the Affiliated Hospital of Xuzhou Medical University from September 2019 to December 2021. Adult patients who received CZA for ≥ 72 hours consecutively were eligible for inclusion. The primary outcome was clinical failure, defined as a composite of 30-day all-cause mortality, microbiological failure and / or failure to resolve or improve signs and symptoms of infection during treatment with CZA. RESULTS: A total of 198 patients with MDR-GNB infections were described and evaluated, including 132 in the carbapenem-resistant Enterobatceriaceae (CRE) cohort and 66 in the Pseudomonas spp. cohort. The main infection sites were lung infection (92.42%), abdominal infection (10.61%), and intracranial infection (10.61%), among which 63 patients (31.82%) were positive for blood culture. Clinical failure, 30-day all-cause mortality and microbiological failure occurred in 61 (30.81%), 33(16.67%) and 11(5.56%) patients, respectively. Body mass index (BMI), acute physiology and chronic health evaluation scoring system (APACHE Ⅱ) and polymicrobial infections were positively associated with clinical outcome failureadjusted OR 1.109, 95%CI 1.017, 1.209; adjusted OR 1.071, 95%CI 1.015, 1.129; adjusted OR 2.844, 95%CI 1.391, 5.814, however, initiation of CZA within 48 hours of admission was protective (adjusted OR 0.424, 95%CI 0.205, 0.879). A total of 15 patients had adverse reactions possibly related to CZA, including 2 cases of rash, 6 cases of nausea and vomiting, and 7 cases of antibiotic-related diarrhea. CONCLUSION: CZA can be used to treat infections caused by a range of MDR-GNB, including Pseudomonas spp. and CRE.

Non-bacteremia liver abscess caused by Burkholderia pseudomallei from a tertiary teaching hospital in Malaysia: a case report and literature review

@#Melioidosis is endemic in Southeast Asia, including Malaysia. Liver abscess is not uncommon in melioidosis, but it is usually associated with bacteremia. We presented a case of a 55-year-old gentleman with underlying end-stage renal failure who presented with non-specific abdominal pain for three months. Initial blood investigations showed leukocytosis and increased C-reactive protein. Computed tomography (CT) of the abdomen revealed multiple hypodense lesions in the liver and spleen. The culture of the liver specimen obtained through the ultrasound-guided isolated Burkholderia pseudomallei. He was given an adjusted dose of intravenous ceftazidime due to underlying renal failure. Melioidosis serology also returned positive for IgM with titer >1:1280. His blood cultures were reported negative three times. Despite on antibiotics for five weeks, there was no significant improvement of the liver abscesses was observed. He was unfortunately infected with the SARS-CoV-2 virus during his admission and passed away due to severe COVID-19 pneumonia.

Real-life comparison of three intravitreal antibiotic drug regimens in endophthalmitis

Purpose: Real?life comparison of three intravitreal drug regimens used in cases of endophthalmitis at a tertiary care center in India. Methods: In this prospective, comparative study, patients of bacterial endophthalmitis were grouped according to intravitreal antibiotic drug regimens into Group 1 (ceftazidime and vancomycin), Group 2 (piperacillin + tazobactam and vancomycin), and Group 3 (imipenem and vancomycin). Forty?eight hours after injection nonresponding/worsening patients underwent vitrectomy. Vitreous samples were subjected to microbiological and pharmacokinetic tests. Results: A total of 64 patients were included and divided into Group 1: 29, Group 2: 20, and Group 3: 15 cases. Also, 75% of patients were post?surgical endophthalmitis, whereas 25% were post?traumatic. Improvement in vision (V90?0) and vision at 3 months (V90) were comparable between the three groups. Visual recovery was poorer in post?traumatic cases. In post?surgical cases, visual recovery was poorer in those presenting beyond 72 h of onset of symptoms (P = 0.0002). Polymerase chain reaction (PCR) positivity (66%) was higher than BACTECTM (33%) and culture (14%). Antibiotic resistance was comparable amongst the three groups. Most patients (62/64) further underwent vitrectomy. Ceftazidime and vancomycin achieved vitreous concentrations more than the minimum inhibitory concentration (MIC) at 48 h after the first injection. Conclusion: The choice of antibiotics did not affect the rate of vitrectomy and final vision in a real?life scenario. Ceftazidime and vancomycin can still be used as first?line intravitreal antibiotics owing to their comparable microbial sensitivity profile and adequate ocular bioavailability

Mecanismos de resistencia bacteriana frente a ceftazidima avibactam. Revisión Sistemática / Mechanisms of bacterial resistance against ceftazidime avibactam. Systematic Review / Mecanismos de resistência bacteriana contra ceftazidima avibactam. Revisão sistemática

La resistencia a los antibióticos representa una problemática a nivel mundial determinada por la capacidad que poseen las bacterias para desarrollar mecanismos de resistencia que les permitan adaptarse y sobrevivir en el entorno en el que se desenvuelven. La combinación ceftazidima-avibactam (CAZ/AVI) desde su aprobación en 2015 por la Food and Drug Administration (FDA) ha demostrado ser muy eficiente frente a bacilos Gram negativos productores de carbapenemasas, pero al igual que otras estrategias frente a bacterias multirresistentes no está exenta del desarrollo de mecanismos de resistencia. Métodos. Se realizó una revisión sistemática de la literatura en las bases de datos Web of Science, PubMed y Scopus siguiendo la metodología PRISMA, se incluyeron 29 artículos en los que se reportó la resistencia a CAZ/AVI en aislados clínicos. Resultados. los mecanismos de resistencia más relevantes fueron las mutaciones en el gen blaKPC en la posición 179 (D179Y) en el bucle conservado omega estimulada por la exposición previa a CAZ/AVI, generando de esta forma nuevas variantes como blaKPC-31 y blaKPC-33. Conclusiones. la evidente presencia de mecanismos de resistencia a CAZ/AVI a pesar de ser una combinación de uso relativamente reciente hace un llamado al uso adecuado de esta combinación.

Antibiotic resistance represents a worldwide problem determined by the ability of batteries to develop resistance mechanisms that allow them to adapt and survive in the environment in which they operate. Since its approval in 2015 by the Food and Drug Administration (FDA), the ceftazidime-avibactam (CAZ/AVI) combination has proven to be very efficient against Gram-negative bacilli that produce carbapenemase, but like other strategies against multiresistant bacteria, it is not exempt from the development of resistance mechanisms. Methods. a systematic review of the literature was carried out in the Web of Science, PubMed and Scopus databases following the PRISMA methodology, including 29 articles in which resistance to CAZ/AVI was reported in clinical isolates. Results. The most relevant resistance mechanisms were mutations in the blaKPC gene at position 179 (D179Y) in the conserved omega loop, stimulated by previous exposure to CAZ/AVI, thus generating new variants such as blaKPC-31 and blaKPC-33. Conclusions. The evident presence of resistance mechanisms to CAZ/AVI, despite being a combination of relatively recent use, calls for the appropriate use of this combination.

A resistência aos antibióticos representa um problema mundial determinado pela capacidade das bactérias desenvolverem mecanismos de resistência que lhes permitem adaptar-se e sobreviver no ambiente em que operam. Desde sua aprovação em 2015 pela Food and Drug Administration (FDA), a combinação ceftazidima-avibactam (CAZ/AVI) tem se mostrado muito eficiente contra bacilos Gram-negativos produtores de carbapenemases, mas como outras estratégias contra bactérias multirresistentes, é não isentos do desenvolvimento de mecanismos de resistência. Métodos. Foi realizada uma revisão sistemática da literatura nas bases de dados Web of Science, PubMed e Scopus seguindo a metodologia PRISMA, incluindo 29 artigos nos quais foi relatada resistência ao CAZ/AVI em isolados clínicos. Resultados. Os mecanismos de resistência mais relevantes foram mutações no gene blaKPC na posição 179 (D179Y) na alça ômega conservada, estimuladas pela exposição prévia ao CAZ/AVI, gerando novas variantes como blaKPC-31 e blaKPC-31. 33. Conclusões. A evidente presença de mecanismos de resistência ao CAZ/AVI, apesar de ser uma combinação de uso relativamente recente, exige o uso adequado dessa combinação.

Susceptibility testing for aztreonam plus ceftazidime/avibactam combination: A general guidance for clinical microbiology laboratories in India

Metallo beta-lactamases-producing Gram-negative infection is often challenging and there is no defined treatment option. In recent years, the combination of aztreonam with ceftazidime-avibactam has gained much clinical attention mainly for MBL-producing Enterobacterales, while MBL-producing P. aeruginosa and A. baumannii are likely to be resistant. A consensus susceptibility testing method for this triple combination has yet to be recommended. Various methods such as broth disk elution, disk stacking, gradient strip stacking, and strip crossing have been proposed for testing this combination. Among them, broth disk elution and strip based testing methods showed good correlation with the broth micro-dilution method.

In vitro activity of ceftazidime-avibactam against Gram-negative strains in patients with complicated urinary tract infection and complicated intra-abdominal infection in Colombia 2014-2018

ABSTRACT Ceftazidime/avibactam (CAZ/AVI) has excellent in vitro activity against enterobacterales and Pseudomonas aeruginosa. The study aimed to analyze the in vitro antimicrobial activity of CAZ/AVI and other antibiotics against isolates of enterobacterales and P. aeruginosa from patients with complicated urinary tract infection (cUTI) and complicated intra-abdominal infection (cIAI) in Colombian hospitals between 2014 and 2018, using the Antimicrobial Testing Leadership and Surveillance (ATLAS) database. Enterobacterales and P. aeruginosa samples were obtained from patients with cUTI and cIAI. Susceptibility was determined using The Clinical and Laboratory Standards Institute (CLSI) breakpoints. Meropenem-non-susceptible isolates were screened for extended-spectrum b-lactamase (ESBL) production. Isolates that were positive for ESBL activity were examined by Multiplex Polymerase Chain Reaction (Multiplex PCR) to detect genotypic resistance. A total of 565 Enterobacterales and 95 P. aeruginosa from patients with cUTI and 345 Enterobacterales and 65 P. aeruginosa from patients with cIAI were isolated. In vitro activity showed susceptibility to CAZ/AVI greater than 99% for Enterobacterales and in lower percentages for P. aeruginosa in cUTI (78.46%) and cIAI (83.33%). CAZ/AVI showed good in vitro activity against multidrug-resistant (MDR) Enterobacterales and P. aeruginosa in patients with cUTI and cIAI.

Impacto da unitarização de ceftazidima + avibactam em um hospital público universitário durante a pandemia de COVID-19 / Impact of ceftazidime + avibactam unitarization in a university public hospital during the COVID-19 pandemic

Introdução: A pandemia de COVID-19 fez aumentar a demanda de medicamentos utilizados em hospitais, como a Ceftazidima + Avibactam. Nesse contexto, a Central de Misturas Intravenosas (CMIV) de um hospital público universitário passou a unitarizar as doses prescritas. O objetivo deste trabalho foi avaliar o impacto da unitarização no consumo deste antibacteriano de alto custo em um hospital público universitário. Métodos: Trata-se de uma análise farmacoeconômica de custos diretos, sobre a utilização de frascos-ampola de Ceftazidima + Avibactam no período de 01/07/2020 a 31/05/2021. Foram unitarizadas todas as doses que correspondiam a uma fração da dose total do frasco-ampola, em Cabine de Segurança Biológica classe II B2. Os frascos-ampola foram utilizados à exaustão, através do compartilhamento e organização dos horários de manipulação. Resultados: O número total de preparos realizados pela CMIV do referido hospital no período foi de 837. O consumo projetado sem a centralização dos preparos seria de 837 (um frasco por dose). Entretanto, o consumo real foi de 437 frascos. A eficiência de unitarização foi de 101%, com economia real de 400 frascos (R$ 244.832,00) para a instituição. Conclusão: A pandemia de COVID-19 sobrecarregou os sistemas de saúde do mundo todo, sendo que a atuação farmacêutica foi fundamental para garantir o acesso aos medicamentos essenciais. A CMIV assumiu a unitarização da Ceftazidima + Avibactam, antibiótico em risco de desabastecimento, gerando um consumo 47,8% menor, contribuindo para o acesso deste medicamento de forma ininterrupta durante os 11 meses avaliados na referida instituição.

Introduction: COVID-19 pandemic has increased the demand for drugs used in hospitals, such as Ceftazidime + Avibactam. In this context, the Central of Intravenous Admixtures (CMIV) of a public university hospital started to unitarize the prescribed doses. The objective of this study was to evaluate the impact of unitarization on the consumption of this high-cost antibacterial in a public university hospital. Methods: This is a pharmacoeconomic analysis of direct costs, on the Ceftazidime + Avibactam vials use, in the period from 07/01/2020 to 05/31/2021. All doses that corresponded to a fraction of the entire vial were unitarized in a Class II B2 Biological Safety Cabin. The vials were used to exhaustion, by sharing them, and organizing the manipulation schedules. Results: The total number of preparations made by the CMIV of that hospital in the period was 837 doses. The projected consumption would be 837 vials (one vial per dose). However, the actual consumption was 437 vials. The unitarization efficiency was of 101%, with real savings of 400 vials (R$ 244,832.00) for the institution. Conclusion: COVID-19 pandemic has overburdened health systems around the world, and pharmaceutical actions have been fundamental to guaranteeing access to essential medicines. CMIV took over the unitarization of Ceftazidime + Avibactam, an antibiotic at risk of shortages, leading to a 47.8% lower consumption, contributing to uninterrupted access to this drug during the 11 months evaluated at that institution.

Antibiotic susceptibility patterns of bacterial isolates of patients with upper respiratory tract infections

Abstract To evaluate the antibiotic susceptibility patterns in URTIs reporting to tertiary hospitals of Lahore. A cross-sectional study employing 259 culture sensitivity reports obtained from tertiary care hospitals of Lahore. Using SPSS, descriptive statistics were used to estimate frequencies and percentages. In URTIs, S. aureus (5%) was the frequent gram-positive isolate followed by MRSA (1.5%) and MSSA (1.5%), while P. aeruginosa (15.8%) was the prevalent gram-negative isolate followed by Klebsiella (13.1%) and E. coli (6.9%). Against P. aeruginosa, ceftazidime (7.7%), cefuroxime/ceftriaxone (4.6%), amoxicillin (4.3%) and ciprofloxacin (4.2%), were tested resistant, while imipenem (11.2%), ciprofloxacin (9.2%), amikacin (9.2%), meropenem/ levofloxacin/gentamicin (8.1%) and piptaz (6.9%) were found sensitive. Against Klebsiella, carbepenems (7.3%), amikacin (6.5%), ciprofloxacin (5.4%) and gentamicin (5%) were tested sensitive, whereas, ceftazidime (8.5%), ceftriaxone (5.8%), cefaclor (5.5%), ampicillin (4.6%), co-amoxiclave (4.2%) and ciftazidime/ciprofloxacin (3.8%) were found resistant. Overall, imipenem (35%), meropenem (30.8%) and amikacin (31.9%) were the three most sensitive antibiotics, while ceftazidime (25.4%), ceftriaxone (19.2%) and ampicillin (18.5%) were the three most resistant antibiotics. Data suggested that P.aeruginosa and Klebsiella, were the most frequent bacterial isolates in URTIs of Lahore. These isolates were resistant to ampicillin, cefuroxime and ceftazidime, but were sensitive to carbapenem and aminoglycosides

Treatment for abdominal infection caused by metallo- β-lactamase-producing Klebsiella pneumoniae in an infant after liver transplantation ：a case report and literature review / 中国药房

OBJECTIVE To investigate the treatment plan for az treonam-resistant metallo- β-lactamase（MBL）-producing Enterobacteriaceae infection in pediatric solid organ transplant recipients. METHODS The clinical data of aztreonam-resistant MBL-producing Klebsiella pneumoniae caused intra-abdominal infection of an infant after liver transplantation were retrospectively analyzed. Abdominal infection occurred after operation. The pathogenic bacterium was MBL-producing K. pneumoniae . The drug sensitivity results showed that the infant was resistant to aztreonam. Based on the results of sensitivity test ，polymyxin B combined with tigecycline were selected as initial regimen. The treatment effect was poor ，with recurrent disease and shock spots. The clinical pharmacist assisted the clinician to formulate treatment regimen of ceftazidime avibactam 0.5 g，q8 h combined with aztreonam 0.18 g，q6 h. Relevant domestic and foreign literature were reviewed ，and the treatment plan of MBL-producing Enterobacteriaceae infection after solid organ transplantation was summarized. RESULTS & CONCLUSIONS The infant was finally cured and discharged with ceftazidime avibatan combined and aztreonam. Several foreign literature reported that ceftazidime avibactam combined with aztreonam could effectively treat the infection caused by aztreonam-resistant MBL-producing Enterobacteriaceae infection in patients with organ transplantation. It is expected to be an effective treatment for aztreonam-resistant MBL-producing Enterobacteriaceae infection in pediatric solid organ transplant recipients.

Costo-efectividad de ceftazidima/avibactam versus colistin + meropenem en el tratamiento de infecciones por enterobacterias resistentes a carbapenémicos en Chile / Cost-effectiveness of ceftazidime/avibactam versus colistin + meropenem for treatment of carbapenemic-resistant enterobacteria infections in Chile

INTRODUCCIÓN: Ceftazidima-avibactam (C/A), ha demostrado reducir las tasas de mortalidad y el riesgo de nefrotoxicidad, comparado con colistin, la terapia convencional. OBJETIVO: Estimar la costo-efectividad de C/A versus colistin + meropenem en el tratamiento de infecciones por Enterobacteriaceae resistentes a carbapenémicos (ERC) en Chile. MATERIAL Y MÉTODOS: Se adaptó un modelo económico tipo árbol de decisión. Se utilizó la perspectiva del pagador público, un horizonte de tiempo de 30 días con extrapolación a la expectativa de vida. La información clínica se derivó de un estudio observacional. Los costos de los medicamentos y de atención corresponden a reportes locales. Los resultados se expresan como razón de costo-efectividad incremental (RCEI) por año de vida ganado (AVG) y por año de vida ajustado por calidad (AVAC) en pesos chilenos y en dólares estadounidenses (US$ 1,00 = $792,2218). RESULTADOS: Se obtuvieron 8,65 y 6,48 AVGs y 6,44 y 4,27 AVACs, para C/A y colistin + meropenem, respectivamente. La RCEI estimada de C/A fue $940.488 (US$1.187,2) por AVG y $938.715 (US$1.184,9) por AVAC. DISCUSIÓN: Dada la falta de publicaciones o evidencia, el modelo se basa en un estudio observacional. C/A reduciría la proporción de muertes e incrementaría los AVG y los AVAC, resultando en una alternativa costo-efectiva versus colistin + meropenem para ERC.

BACKGROUND: Ceftazidime-avibactam (C/A), has shown reduction in mortality rates and risk of nephrotoxicity, compared to colistin, conventional therapy. AIM: To estimate the cost-effectiveness of C/A versus colistin + meropenem in the treatment of infections due to carbapenem-resistant Enterobacteriaceae (CRE) in Chile. METHODS: An economic decision tree type model was adapted. The perspective of the public payer was used with a time horizon of 30 days and extrapolation to life expectancy. The clinical information was derived from an observational study. Medication and care costs correspond to local reports. The results are expressed as incremental cost-effectiveness ratio (ICER) per life year gained (LYG) and per quality adjusted life year (QALY) in Chilean pesos and US dollars (US$ 1.00 = $792.2218). RESULTS: 8.65 and 6.48 LYGs and 6.44 and 4.27 QALYs were obtained, for C/A and colistin + meropenem, respectively. The estimated ICER for C/A was $940,488 (US$1,187.2) per AVG and $938,715 (US$1,184.9) per QALY. DISCUSSION: Given the lack of publications or evidence, the model is based on an observational study. C/A would reduce the death rate and increase LYGs and QALYs, resulting in a cost-effective alternative vs. colistin + meropenem for CRE.

Effect of donor-derived infection on clinical prognosis of kidney transplant recipients / 器官移植

Objective To evaluate the effect of donor-derived infection (DDI) on clinical prognosis of kidney transplant recipients. Methods Clinical data of 82 donors from donation after citizen's death and 148 kidney transplant recipients were retrospectively analyzed. According to the culture results of the lavage fluid of donor kidney, all recipients were divided into the lavage fluid culture of donor kidney positive group (positive group, n=92) and lavage fluid culture of donor kidney negative group (negative group, n=56). All recipients were assigned into the DDI group (n=19) and non-DDI group (n=129) according to whether they developed DDI or not. The distribution and composition ratio of positive strains in the lavage fluid of donor kidney were analyzed. The incidence of postoperative infection and other complications was assessed in the recipients. Perioperative conditions of the recipients were statistically compared between the DDI and non-DDI groups. The treatment efficacy and clinical prognosis of DDI recipients were evaluated. Results Among 148 recipients, 92 obtained positive culture results in the lavage fluid of donor kidney. A total of 131 pathogenic strains were isolated, including 41.2% (54/131) of Gram-positive cocci, 48.9% (64/131) of Gram-negative bacilli and 9.9%(13/131) of fungi. Among 148 recipients, 52 cases were infected. And 45% (41/92) and 20% (11/56) of the recipients were infected in the positive and negative group, respectively. Statistical significance was noted between two groups (P=0.002). Surgical site was the most common infection site in 52 infected recipients, followed by the urinary system. Nineteen recipients developed DDI with an incidence rate of 12.8% and fatality of 16%. Compared with the non-DDI recipients, DDI recipients had significantly higher graft loss rate and fatality, and longer postoperative hospital stay (all P < 0.05). Eight cases presented with carbapenem-resistant Klebsiella pneumoniae (CRKP) infection, after treatment with tigecycline and/or polymyxin and carbapenems, 3 cases died, and 3 underwent kidney graft resection. In the other 8 recipients with CRKP infection, 2 cases were treated with ceftazidime-avibactam (CAZ-AVI) alone, 3 treated with CAZ-AVI combined with carbapenems, and 3 initially treated with tigecycline combined with carbapenems followed by CAZ-AVI for salvage treatment. After corresponding treatment, the recipients achieved long-term survival. Conclusions DDI may lead to severe complications, while early specific antibacterial treatment plays a positive role.

Endophthalmitis Caused by Mixed Infections in Silicone Oil-filled Eye:One Case Report / 中国医学科学院学报

The incidence of endophthalmitis after vitrectomy is extremely low,especially lower in silicone oil-filled eyes.Silicone oil exerts a toxic effect on the cell membranes of microorganisms and leads to the lack of nutrients.It is thus believed to inhibit the growth of bacteria and fungi.Endophthalmitis induced by mixed bacteria in silicone oil-filled eye has been rarely reported.We reviewed the clinical manifestations,diagnosis,and treatment of a patient with endophthalmitis caused by mixed infection of

The efficacy and safety of ceftazidime/avibactam therapy on carbapenem-resistant Enterobacteriaceae infections: a Meta-analysis / 药学实践杂志

Objective To systematically evaluate the efficacy and safety of ceftazidime/avibactam(CAZ/AVI) in the treatment of carbapenem-resistant Enterobacteriaceae(CRE) or carbapenem-resistance Klebsiella pneumonia (CRKP), and to provide evidence-cased reference for clinic therapy. Methods A comprehensive literature search from PubMed, Embase, the Cochrane Library, CBM, CNKI and VIP database was conducted for the CAZ/AVI therapy on CRE/CRKP infections published before May.2020. Two reviewers independently screened literatures according to the inclusion and exclusion criteria, extracted data, and assessed the methodological quality of the included studies. The results were analyzed by RevMan 5.3 statistical software. Results Five studies in English involving 392 patients were included for the analysis. In terms of effectiveness, the results showed CAZ/AVI group significantly increased the clinical cure rate[OR=3.57, 95% CI (2.03, 6.26), P<0.00001] compared with the control group. Also CAZ/AVI group significantly decreased the 28/30 day all-cause mortality [OR=0.27, 95% CI (0.14, 0.50), P<0.0001]. There were no significant difference between the two groups in the clinical remission rate [OR=1.92, 95% CI (0.93, 3.97), P=0.08] and the infection recurrence rate [OR=0.44, 95% CI (0.11, 1.85), P=0.26]. In terms of safety, the incidence of adverse events in CAZ/AVI group were lower than those in control group [OR=0.29, 95% CI (0.10, 0.80), P=0.02]. There was no significant difference between two groups in the incidence of serious adverse events[OR=0.33, 95% CI (0.09, 1.19), P=0.09]. Conclusion The current evidence shows that CAZ/AVI therapy has advantage in survival rate for the treatment of CRE/CRKP infections without increase of SAEs. Limited by the quality and quantity of the included studies, the above conclusions need to be verified with more high-quality RCTs.

Analysis of polymer impurities in ceftazidime raw materials and preparations / 药学学报

To establish a method for the determination of polymer impurities in ceftazidime raw materials and preparations, a ceftazidime degradation solution containing polymer impurities was prepared by forced polymerization. Polymer impurities in the degradation solution were separated and identified by high performance gel chromatography and the column switching-LC-MSn method. A new RP-HPLC method for ceftazidime polymer was established and validated with a Phenomenex Gemini-C18 column using a mobile phase gradient elution of 0.02 mol·L-1 phosphate buffer, methanol and acetonitrile. The results showed that when using this high performance gel chromatography method some small molecular weight impurities were co-eluted with the polymers, resulting in a poor specificity and poor quantitative accuracy. But when using the RP-HPLC method, four polymer impurities were detected in the 25-45 min time range with good specificity, sensitivity and robustness, including two ceftazidime dimers, trimers, and derivatives. Therefore, the described RP-HPLC method is suitable for the quality control of polymer impurities in ceftazidime, and ceftazidime degradation solution can be used as suitable solution for analysis of ceftazidime polymers.