Pharmaceutical care for a patient with paroxysmal spasms of extremities caused by ceftazidime-avibactam / 中国药房

OBJECTIVE To explore the role of clinical pharmacists in identifying paroxysmal spasms caused by drugs， and provide reference for rational drug use. METHODS Retrospective analysis was conducted on pharmaceutical care provided by clinical pharmacists for a patient with ceftazidime-avibactam （CZA-AVI） induced paroxysmal spasms. The clinical pharmacists identified， analyzed and summarized the clinical manifestations， risk factors and treatment methods of the nervous system toxicity caused by antibacterial drugs. According to the patient’s clinical symptoms and test results， the clinical pharmacists recommended temporarily discontinuing the use of polymyxin B and montelukast sodium， and halving the dose of CZA-AVI. The physicians did not adopt the recommendation to halve the dose of CZA-AVI， and when the patient’s neurologic toxicity did not improve， the clinical pharmacists again recommended discontinuing CZA-AVI， which was accepted by the physicians. RESULTS Clinical pharmacists analyzed the condition and checked related drugs that caused paroxysmal spasms of extremities one by one， and finally determined that CZA-AVI might be the drug that caused paroxysmal spasms of extremities in the patient. After stopping the drug， the patient’s symptoms improved and was transferred to a community hospital for rehabilitation treatment. CONCLUSIONS The dose of CZA-AVI should be adjusted according to the renal function and the neurotoxicity should be guarded against， especially for patients with advanced age， renal insufficiency， and the combined use of multiple drugs related to nephrotoxicity and neurotoxicity.

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.

Advances in the treatment of KPC-producing Klebsiella pneumoniae infec-tion / 中国感染控制杂志

In recent years,the isolation rate of carbapenem-resistant Klebsiella pneunoniae(CRKP)in China has increased year by year.Due to its multidrug resistance and high mortality in patients,CRKP brings severe challen-ges to the clinical treatment.The major mechanism of drug resistance in CRKP is the production of carbapenemases,with Ambler A,B,and D being the common types while Ambler type C comparativly rare.Klebsiella pneumoniae carbapenemase(KPC)is the most common carbapenemase,which belongs to type A.KPC-producing Klebsiella pneumoniae(KPC-KP)widely spreads in the world,with very limited number of effective clinical drugs.In this re-view,advances in the treatment KPC-KP were summarized to provide reference for clinical treatment.

Septicaemia due to Vibrio vulnificus: A tropical infection not to be taken lightly

@#Vibrio vulnificus is a halophilic gram-negative bacillus that can cause fulminant septicaemia in immunocompromised patients. A 67-year-old man who was immunosuppressed as a result of cytotoxic chemotherapy presented with a brief history of fever, lethargy, myalgia, and reduced oral intake. He had recently travelled to the beach to consume seafood. His blood pressure was 81/47 mm Hg, necessitating fluid resuscitation followed by inotropic support and admission to the intensive care unit. His blood culture was positive for curved gram-negative bacilli. The isolate was oxidase-positive and produced an acid butt with an alkaline slant in triple sugar iron agar. Matrix-assisted laser desorption ionization-time of flight mass spectrometry conclusively identified the isolate as V. vulnificus. Intravenous ceftazidime plus ciprofloxacin were administered, and by the fifth day of admission, he was successfully transferred out to the general ward. In total, the patient completed a 14-day course of antibiotic therapy.

Novas variantes de KPC em isolados do Complexo Klebsiella pneumoniae resistentes à ceftazidima-avibactam / New KPC variants in ceftazidime-avibactam-resistant K. pneumoniae Complex isolates

O Complexo K. pneumoniae (C-Kp) é o principal grupo de bacilos Gram-negativos responsáveis por infecções nosocomiais graves em todo o mundo e o tratamento empírico dessas infecções usualmente inclui os carbapenêmicos. O principal mecanismo de resistência a essa classe de antimicrobianos é a expressão de carbapenemases, e no Brasil, mais frequentemente as do tipo KPC. Em março de 2019 a ceftazidima-avibactam foi disponibilizada para uso clínico no Brasil, sendo amplamente utilizada no tratamento infecções causadas por bacilos gram-negativos produtores de KPC. Diversos países já relataram a presença de K. pneumoniae produtores de KPC resistentes à ceftazidima-avibactam. No entanto, há poucos relatos dessa ocorrência no Brasil. O objetivo deste trabalho foi caracterizar genotipicamente e fenotipicamente isolados do C-Kp produtores de KPC, resistentes à ceftazidima-avibactam. No período de julho/2019 a julho/2021, 46 isolados do C-Kp, um por paciente, foram detectados em diferentes sítios de infecção ou culturas de vigilância de pacientes internados em hospitais privados de seis estados brasileiros. Os isolados tiveram seu genoma completo sequenciado nas plataformas MiSeq e MinION para determinação da variante alélica de blaKPC e avaliação do seu contexto genético. As taxas de resistência ao ertapenem e à ceftazidima-avibactam foram calculadas a partir de banco de dados. A clonalidade dos isolados foi avaliada por PFGE e MLST. A localização plasmidial do gene blaKPC foi confirmada por conjugação e/ou transformação. A concentração inibitória mínima (CIM) para betalactâmicos foi determinada por microdiluição em caldo segundo o BrCAST. Ensaios imunocromatográficos, NG-Test CARBA-5 e O.K.N.V.I. RESIST-5, foram avaliados quanto à sua performance na detecção de variantes KPC. A taxa de resistência ao ertapenem entre isolados do C-Kp aumentou 15,6% em 2019 para 27,3% em 2021. A taxa de resistência à ceftazidima-avibactam entre isolados do C-Kp resistentes ao ertapenem aumentou de 4,2% em 2019 para 17,2% em 2021. Onze isolados apresentaram novas variantes de KPC designadas KPC-103 a KPC-108 e KPC-139 a KPC-143. Os demais isolados apresentavam variantes de KPC já descritas, sendo a KPC-33 a variante mais frequente (36%). Quinze grupos clonais foram identificados, sendo que a maioria dos isolados pertencia ao ST11. O grupo clonal A foi o mais numeroso e pertencia ao ST258. A principal variante detectada nesse grupo foi a KPC-33. Diferentes grupos de incompatibilidade foram identificados em plasmídeos alberguando blaKPC, sendo os grupos IncN (n=12) e IncF, com replicons FII(K)-FIB (n=11), os grupos mais frequentes, seguido de InX3-IncU (n=9) e IncQ1 (n=1). Dos 46 isolados resistentes à ceftazidima-avibactam, 36 foram capazes de transferir o gene blaKPC para cepas receptoras. A maioria dos isolados foi sensível dose padrão ou sensível aumentabdo exposição ao meropenem e apresentaram redução significativa da CIM quando o avibactam foi adicionado ao aztreonam. O NG-Test CARBA-5 detectou 12 das 24 variantes testadas enquanto que o O.K.N.V.I. RESIST-5 detectou apenas nove variantes. A grande diversidade de variantes KPC, e a predominância do grupo clonal ST11, e da KPC- 33 retratam um cenário preocupante no Brasil

The K. pneumoniae Complex (C-Kp) is the main group of gram-negative bacilli responsible for serious nosocomial infections worldwide and the empirical treatment of these infections usually includes carbapenems. The main mechanism of resistance to this class of antimicrobials is the expression of carbapenemases, and in Brazil, more frequently the KPC type. In March 2019, ceftazidime-avibactam was available for clinical use in Brazil, being widely used to treat infections caused by KPC-producing gram-negative bacilli. Several countries have already reported the presence of KPC-producing K. pneumoniae resistant to ceftazidime-avibactam; however, there are few reports of this occurrence in Brazil. This work aimed to genotypically and phenotypically characterize KPC-producing C-Kp isolates resistant to ceftazidimeavibactam. From July 2019 to July 2021, 46 C-Kp isolates, one per patient, were detected in different sites of infection or surveillance cultures from patients admitted to private hospitals in six Brazilian states. The isolates had their complete genome sequenced on the MiSeq and MinION platforms to determine the allelic variant of blaKPC and evaluate its genetic context. Resistance rates to ertapenem and ceftazidime-avibactam were calculated from a database. The clonality of the isolates was evaluated by PFGE and MLST. The plasmid location of the blaKPC gene was confirmed by conjugation and/or transformation. The minimal inhibitory concentrations for beta-lactams were determined by broth microdilution according to BrCAST. Immunochromatographic assays, NG-Test CARBA-5 and O.K.N.V.I. RESIST-5, were evaluated for its performance in detecting KPC variants. The resistance rate to ertapenem among C-Kp isolates increased from 15.6% in 2019 to 27.3% in 2021. The resistance rate to ceftazidime-avibactam among ertapenem-resistant C-Kp isolates increased from 4.2% in 2019 to 17.2% in 2021. Eleven isolates showed new KPC variants designated KPC-103 to KPC-108 and KPC-139 to KPC-143. The remaining isolates presented previously described KPC variants, with KPC-33 being the most common variant (36%). Fifteen clonal groups were identified, with most isolates belonging to ST11. Different incompatibility groups were identified in plasmids harboring blaKPC, with the IncN (n=12) and IncF groups, with FII(K)-FIB(n=11) replicons, being the most frequent groups, followed by InX3-IncU (n= 9) and IncQ1 (n=1). All IncX3-IncU plasmids were approximately 46 kb in size and were identified among isolates belonging to the largest identified clonal group (A) and ST258. The main variant detected in this group was KPC-33. Of the 46 ceftazidime-avibactam-resistant isolates, 36 were able to transfer the blaKPC gene to recipient strains. Most isolates were susceptible standard dose or susceptible increased exposure to meropenem and showed a significant decrease in MIC when avibactam was added to aztreonam. The NG-Test CARBA-5 was able to detect 12 of the 24 variants evaluated while the O.K.N.V.I. RESIST-5 detected only nine variants. The great diversity of KPC variants, the predominance of the ST11 clonal group, and KPC-33 portray a worrying scenario in Brazil

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 / Ceftazidime/avibactam versus other antibiotics for the treatment of KPC carbapenemase-producing Enterobacterales bacteremia: real-life data from a university hospital in 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 / Use of ceftazidime-avibactam in a preterm infant with urinary tract infection with bacteremia caused by carbapenemase-producing Klebsiella pneumoniae

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.

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.

Drug resistance mechanism of carbapenem-resistant Klebsiella pneumoniae to ceftazidime/avibactam and progress in clinical treatment / 中华微生物学和免疫学杂志

Klebsiella pneumoniae is one of the common pathogens causing hospital-acquired infection. With the wide use of carbapenem in recent years, carbapenem-resistant Klebsiella pneumoniae (CRKP) has emerged around the world. Carbapenemase production is the main cause of resistance to carbapenem antibiotics in Klebsiella pneumoniae. More than 70% of Klebsiella pneumoniae strains produce carbapenemase. Ceftazidime/avibactam (CAZ/AVI) can effectively treat CRKP infection, especially those caused by CRKP that can produce Klebsiella pneumoniae carbapenemase (KPC) or oxaclillinase (OXA)-48. However, it has been reported that CAZ/AVI-resistant CRKP strains have emerged. In this paper, the epidemiology, risk factors, resistance mechanism and treatment of CAZ/AVI-resistant CRKP were summarized to provide reference for clinical treatment.

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.

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).

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.

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.

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

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.