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.

Proposal of a clinical score to stratify the risk of multidrug-resistant gram-negative rods bacteremia in cancer patients

ABSTRACT Introduction: Multidrug-resistant gram-negative rods (MDR GNR) represent a growing threat for patients with cancer. Our objective was to determine the characteristics of and risk factors for MDR GNR bacteremia in patients with cancer and to develop a clinical score to predict MDR GNR bacteremia. Material and Methods: Multicenter prospective study analyzing initial episodes of MDR GNR bacteremia. Risk factors were evaluated using a multiple logistic regression (forward-stepwise selection) analysis including variables with a p < 0.10 in univariate analysis. Results: 394 episodes of GNR bacteremia were included, with 168 (42.6 %) being MDR GNR. Five variables were identified as independent risk factors: recent antibiotic use (OR = 2.8, 95 % CI 1.7-4.6, p = 0.001), recent intensive care unit admission (OR = 2.9, 95 % CI 1.1-7.8, p = 0.027), hospitalization ≥ 7 days prior to the episode of bacteremia (OR = 3.5, 95 % CI 2-6.2, p = 0.005), severe mucositis (OR = 5.3, 95 % CI 1.8-15.6, p = 0.002), and recent or previous colonization/infection with MDR GNR (OR = 2.3, 95 % CI 1.2-4.3, p = 0.028). Using a cut-off value of two points, the score had a sensitivity of 66.07 % (95 % CI 58.4-73.2 %), a specificity of 77.8 % (95 % CI 71.4-82.7 %), a positive predictive value of 68 % (95 % CI 61.9-73.4 %), and a negative predictive value of 75.9 % (95 % CI 71.6-79.7 %). The overall performance of the score was satisfactory (AUROC 0.78; 95 % CI 0.73-0.82). In the cases with one or none of the risk factors identified, the negative likelihood ratio was 0.18 and the post-test probability of having MDR GNR was 11.68 %. Conclusions: With the growing incidence of MDR GNR as etiologic agents of bacteremia in cancer patients, the development of this score could be a potential tool for clinicians.

Changes in Renal Function by Nebulized Colistimethate Treatment

BACKGROUND: Nebulized colistimethate is increasingly used, because there are problems such as renal dysfunction and low distribution within the lungs when colistimethate is administered intravenously. This study was designed to compare and analyze the changes in renal function by of nebulized colistimethate treatment for its safe administration. METHODS: This study retrospectively reviewed the electronic medical records of adult patients above 19 years old, receiving only the nebulized colistimethate at least 4 days in Yonsei university health system from Nov 2014 to Aug 2015. Acute kidney injury (AKI) was determined by using the RIFLE criteria (Risk, Injury, Failure, Loss and End-stage renal disease) according to serum creatinine (SCr) levels before and after use of nebulized colistimethate. RESULTS: 48 patients were included our study and their SCr increased significantly after nebulized colistimethate treatment (SCr₀ vs. SCr₁; 0.85±0.80 vs. 1.00±0.82 mg/dL, n=48, p0.05). The study has a significance in that it reviewed the safety of nebulized colistimethate only treatment to national patients, analyzing its nephrotoxicity. It has confirmed that nebulized colistimethate is a safer method than intravenous injection, and requires to establish a guideline for the use of nebulized colistimethate in further studies with broader patient groups. (a): SCr Male 0.68-1.19 mg/dL, Female 0.49-0.91 mg/dL

Infection with multidrug-resistant gram-negative bacteria in a pediatric oncology intensive care unit: risk factors and outcomes / Infecção por bactérias gram-negativas multirresistentes em uma unidade de terapia intensiva pediátrica oncológica: fatores de risco e resultados

ABSTRACT OBJECTIVE: This study aimed at evaluating the predictors and outcomes associated with multidrug-resistant gram-negative bacterial (MDR-GNB) infections in an oncology pediatric intensive care unit (PICU). METHODS: Data were collected relating to all episodes of GNB infection that occurred in a PICU between January of 2009 and December of 2012. GNB infections were divided into two groups for comparison: (1) infections attributed to MDR-GNB and (2) infections attributed to non-MDR-GNB. Variables of interest included age, gender, presence of solid tumor or hematologic disease, cancer status, central venous catheter use, previous Pseudomonas aeruginosa infection, healthcare-associated infection, neutropenia in the preceding 7 days, duration of neutropenia, length of hospital stay before ICU admission, length of ICU stay, and the use of any of the following in the previous 30 days: antimicrobial agents, corticosteroids, chemotherapy, or radiation therapy. Other variables included initial appropriate antimicrobial treatment, definitive inadequate antimicrobial treatment, duration of appropriate antibiotic use, time to initiate adequate antibiotic therapy, and the 7- and 30-day mortality. RESULTS: Multivariate logistic regression analyses showed significant relationships between MDR-GNB and hematologic diseases (odds ratio [OR] 5.262; 95% confidence interval [95% CI] 1.282-21.594; p = 0.021) and healthcare-associated infection (OR 18.360; 95% CI 1.778-189.560; p = 0.015). There were significant differences between MDR-GNB and non-MDR-GNB patients for the following variables: inadequate initial empirical antibiotic therapy, time to initiate adequate antibiotic treatment, and inappropriate antibiotic therapy. CONCLUSIONS: Hematologic malignancy and healthcare-associated infection were significantly associated with MDR-GNB infection in this sample of pediatric oncology patients.

RESUMO OBJETIVO: Este estudo visou a avaliar os preditores e resultados associados às infecções por bactérias gram-negativas multirresistentes (BGN-MR) em uma unidade de terapia intensiva pediátrica oncológica (UTIP). MÉTODOS: Foram coletados dados com relação a todos os episódios de infecção por BGN que ocorreram em uma UTIP entre janeiro de 2009 e dezembro de 2012. As infecções por BGN foram divididas em dois grupos para comparação: 1) infecções atribuídas a BGN-MR e 2) infecções atribuídas a BGN não multirresistente. As variáveis de interesse incluíram idade, sexo, presença de tumor sólido ou malignidade hematológica, câncer, uso de cateter venoso central, infecção anterior por Pseudomonas aeruginosa, infecção hospitalar, neutropenia nos sete dias anteriores, duração da neutropenia, tempo de internação antes da UTI, duração da internação na UTI e uso de quaisquer dos seguintes nos 30 dias anteriores: agentes antimicrobianos, corticosteroides, quimioterapia ou radioterapia. Outras variáveis incluíram: tratamento antimicrobiano inicial adequado, tratamento antimicrobiano definitivo inadequado, duração do uso de antibióticos adequados, tempo de início da terapia antibiótica adequada, mortalidade em sete dias e mortalidade em 30 dias. RESULTADOS: As análises de regressão logística multivariada mostraram relações significativas entre as BGN-MR e as doenças hematológicas (razão de chance (RC) 5,262; intervalo de confiança de 95% (IC de 95%) 1,282-21,594; p = 0,021) e infecções hospitalares (RC 18,360; IC de 95% 1,778-189,560; p = 0,015). Houve diferenças significativas entre os pacientes com BGN-MR e BGN não MR com relação às seguintes variáveis: recebimento de terapia antibiótica empírica inicial inadequada, tempo para início do tratamento antibiótico adequado e recebimento de terapia antibiótica inadequada. CONCLUSÕES: A malignidade hematológica e a infecção hospitalar foram significativamente associadas à infecção por BGN-MR nessa amostra de pacientes pediátricos oncológicos.

Phenotypic identification & molecular detection of blandm-1 gene in multidrug resistant Gram-negative bacilli in a tertiary care centre.

Background & objectives: Carbapenemase-producing Enterobacteriaceae isolates have been increasingly identified worldwide. Though molecular data regarding New Delhi metallo-beta-lactamase-1 (NDM-1) producers are available, data regarding their rate of infection in a hospital setting and percentage among different clinical isolates are scarce. Hence, this study was undertaken to determine the occurrence of blaNDM-1 gene among clinical isolates of multidrug resistant Gram-negative bacilli (MDRGNB) in a tertiary care centre in Bangalore, Karnataka, India. Methods: A total of 74 MDRGNB isolates were studied. These were screened for MBL production by phenotypic assays such as double disk synergy test (DDST) and Modified Hodge’s test (MHT). PCR was performed for the molecular detection of the gene and antibiograms were confirmed by automated bacteriology system. Results: Of the 74 MDRGNB isolates, 34 were positive for blaNDM-1 gene. All isolates were resistant to aztreonam and two isolates were resistant to tigecycline. Complete resistance to the tested carbapenems was seen in 28 (82.35%) of the positive isolates whereas variable carbapenem resistance was seen in six (17.64%) of the positive clinical isolates. Of the total 34 PCR positive isolates, 33 (97.05%) NDM-1 producers were identified by DDST and 26 (76.47%) by MHT as producers of MBL. Interpretation & conclusions: A high percentage of plasmid encoded NDM was noted in MDRGNB. Phenotypic and molecular screening should be employed along with routine antimicrobial susceptibility testing to reflect the true number of metallo-beta-lactamase producers.

Vigilancia institucional de la susceptibilidad antimicrobiana en patógenos de interés clínico / Institutional vigilance of antimicrobial susceptibility in pathogens of clinical interest

Introducción. El incremento en la resistencia de los microorganismos a los antibióticos ha provocado un aumento en la morbimortalidad de las infecciones, un mayor uso de antibióticos y el exceso en gastos de hospitalización. Por lo tanto, el objetivo de este trabajo fue describir la frecuencia de microorganismos patógenos y sus patrones de susceptibilidad bacteriana en cultivos de sangre, orina y de otros fluidos corporales en un hospital pediátrico de tercer nivel. Métodos. Se incluyeron en el estudio cepas de cultivos de sangre, orina, líquido cefalorraquídeo y otros, como pleural, pericárdico y peritoneal, de enero de 2010 a junio de 2011. La identificación y la susceptibilidad se obtuvieron utilizando el equipo Vitek 2XL, de acuerdo con las recomendaciones del Clinical and Laboratory Standards Institute . Resultados. Se aislaron e identificaron 7708 bacterias de 27,209 cultivos de muestras biológicas. Los microorganismos más frecuentes fueron Staphylococcus coagulasa negativa, Escherichia coli, Enterococcus spp, Staphylococcus aureus, Pseudomonas aeruginosa y Klebsiella pneumoniae . La actividad antimicrobiana en contra de los diferentes patógenos fue variable. Escherichia coli presentó la mayor resistencia a trimetoprima-sulfametoxazol (74%) y ampicilina-sulbactam (68%). Las mejores opciones resultaron nitrofurantoína e imipenen, con 84 y 100% de sensibilidad. La resistencia de Enterococcus faecium fue de 58% a vancomicina. Streptococcus pneumoniae presentó 100% de sensibilidad a vancomicina. Conclusiones. La frecuencia de patógenos provenientes de diferentes fluidos corporales no ha variado considerablemente. Sin embargo, el cambio más notable se observó en la resistencia, tanto en Gram positivos como en Gram negativos, en contra de los fármacos convencionales, así como en los considerados de amplio espectro.

Background. The increased resistance of microorganisms to antibiotics has led to an increase in morbidity and mortality from infections, increased use of antibiotics and excessive hospitalization costs. Therefore, the aim of this study was to describe the frequency of pathogens and bacterial susceptibility patterns in cultures of blood, urine and other body fluids in a tertiary pediatric hospital. We also aimed to determine the patterns of resistance in pathogens of clinical interest isolated in blood, urine and other sterile liquids in a pediatric teaching center and third-level hospital. Methods. The Institutional Antimicrobial Surveillance Program was established to monitor the predominant pathogens and antimicrobial susceptibility patterns of infections such as bacteremia, pneumonia and urinary infections. The species of each isolate was determined according to routine methodology and Vitek system from January 2010 to June 2011. Antimicrobial agents and susceptibility testing were determined using the Vitek 2XL according to the Clinical and Laboratory Standards Institute. Results. We recovered 7708 isolates from 27,209 cultures (28.3%). Gram negative represented 52.7%. A rank order showed Staphylococcus coagulase-negative , Escherichia coli, Enterococcus spp ., Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae and others. The antimicrobial susceptibility of the most frequently encountered pathogens was variable. E. coli showed the highest resistance to trimethopim-sulfamethoxazole and ampicillin-sulbactam (74 and 68%, respectively) finding the best option to be nitrofurantoin and imipenem with 84 and 100% sensitivity, respectively. Enterococcus faecium resistance was 58% vancomycin, and Streptococcus pneumoniae showed 100% sensitivity to vancomycin. Conclusions. This study emphasizes the problem of resistance and the needs to select an appropriate broad-spectrum empirical regimen guided by the knowledge of pathogen occurrences and local/regional/global resistance patterns. Such practices require the interrelation between clinical microbiology laboratories and hospital pharmacies.