scholarly journals Treatment of Extensively Drug-Resistant (XDR) Acinetobacter in US Veterans’ Affairs (VA) Medical Centers

2021 ◽  
Vol 1 (S1) ◽  
pp. s71-s71
Author(s):  
Margaret Fitzpatrick ◽  
Katie Suda ◽  
Linda Poggensee ◽  
Amanda Vivo ◽  
Geneva Wilson ◽  
...  
Keyword(s):  
Propensity Score ◽  
Combination Therapy ◽  
Medical Center ◽  
Therapy Group ◽  
Veterans Affairs ◽  
Drug Resistant ◽  
Term Care ◽  
Gram Negative ◽  
Extensively Drug Resistant ◽  
Significant Difference

Background: Infections caused by Acinetobacter spp are often healthcare acquired and associated with high mortality. Extensively drug-resistant (XDR) Acinetobacter are nonsusceptible to at least 1 agent in all but 2 or fewer antibiotic classes. Few of the new antibiotics targeting multidrug-resistant gram-negative bacteria are effective against XDR Acinetobacter. Recent national guidelines for treatment of resistant gram-negative infections do not include Acinetobacter, leaving a knowledge gap in best practices. Methods: This retrospective cohort study included microbiology, clinical, and pharmacy data from all patients hospitalized between 2012 and 2018 at any Veterans’ Affairs medical center who had cultures that grew XDR Acinetobacter spp. Bivariate unadjusted analyses compared clinical outcomes by monotherapy versus combination therapy. Using mixed-effects ordinal logistic regression, propensity score–adjusted models accounting for severity of illness and other variables associated with treatment were fit to compare outcomes. Results: Of 11,546 patients with 15,364 cultures that grew Acinetobacter spp, 408 patients (3.5%) had 666 cultures (4.3%) with XDR Acinetobacter. Moreover, 276 of these patients (67.6%) had gram-negative targeted antibiotic treatment within −2 to +5 days from the culture. Furthermore, 118 patients (42.8%) received monotherapy, most commonly piperacillin-tazobactam (n = 54, 45.7%) or an anti-Pseudomonas cephalosporin (n = 21, 17.8%). Also, 158 (57.2%) patients received combination therapy, most commonly a carbapenem (n = 93, 58.9%) and/or polymyxin (n = 68, 43.0%). Moreover, 41 patients (25.9%) received both a carbapenem and polymyxin. In both unadjusted and adjusted analyses, there were no significant differences in the odds of 30-day mortality (aOR, 1.43; 95% CI, 0.86–2.38) or 1-year mortality (aOR, 1.04; 95% CI, 0.68–1.60) between combination therapy and monotherapy groups. Among 264 patients (96%) whose cultures occurred during an inpatient or long-term care admission, unadjusted analyses showed increased odds of in-hospital mortality (OR, 1.89; 95% CI, 1.08–3.29) and longer postculture length of stay in the combination therapy group: median, 23 days (IQR, 11–57) versus 14 days (IQR, 7–32) (P = .02). However, with propensity score adjustment, these associations were no longer significant. Furthermore, there was no significant difference in odds of 90-day readmission between groups in either unadjusted or adjusted analyses (aOR, 1.20; 95% CI, 0.74–1.95). Conclusions: In this large national cohort of patients with XDR Acinetobacter cultures, more patients received combination therapy than monotherapy, and carbapenems and polymyxins were the most-used classes. However, there were no significant differences in outcomes between patients receiving combination therapy and monotherapy, suggesting lack of clinical benefit to the common practice of treating XDR Acinetobacter infections with multiple antibiotics. Further research is needed to determine optimal treatment strategies for this pathogen.Funding: NoDisclosures: None

scholarly journals Clinical Efficacy of Polymyxin Monotherapy versus Nonvalidated Polymyxin Combination Therapy versus Validated Polymyxin Combination Therapy in Extensively Drug-Resistant Gram-Negative Bacillus Infections

2016 ◽  
Vol 60 (7) ◽  
pp. 4013-4022 ◽  
Author(s):  
Bingxuan Cai ◽  
Yiying Cai ◽  
Yi Xin Liew ◽  
Nathalie Grace Chua ◽  
Jocelyn Qi-Min Teo ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Multivariable Analysis ◽  
Apache Ii Score ◽  
Drug Resistant ◽  
Risk Of Infection ◽  
Gram Negative ◽  
Extensively Drug Resistant ◽  
Increased Risk ◽  
Related Mortality

ABSTRACTPolymyxins have emerged as a last-resort treatment of extensively drug-resistant (XDR) Gram-negativeBacillus(GNB) infections, which present a growing threat. Individualized polymyxin-based antibiotic combinations selected on the basis of the results ofin vitrocombination testing may be required to optimize therapy. A retrospective cohort study of hospitalized patients receiving polymyxins for XDR GNB infections from 2009 to 2014 was conducted to compare the treatment outcomes between patients receiving polymyxin monotherapy (MT), nonvalidated polymyxin combination therapy (NVCT), andin vitrocombination testing-validated polymyxin combination therapy (VCT). The primary and secondary outcomes were infection-related mortality and microbiological eradication, respectively. Adverse drug reactions (ADRs) between treatment groups were assessed. A total of 291 patients (patients receiving MT,n= 58; patients receiving NVCT,n= 203; patients receiving VCT,n= 30) were included. The overall infection-related mortality rate was 23.0% (67 patients). In the multivariable analysis, treatment of XDR GNB infections with MT (adjusted odds ratio [aOR], 8.49; 95% confidence interval [CI], 1.56 to 46.05) and NVCT (aOR, 5.75; 95% CI, 1.25 to 25.73) was associated with an increased risk of infection-related mortality compared to that with treatment with VCT. A higher Acute Physiological and Chronic Health Evaluation II (APACHE II) score (aOR, 1.14; 95% CI 1.07 to 1.21) and a higher Charlson comorbidity index (aOR, 1.28; 95% CI, 1.11 to 1.47) were also independently associated with an increased risk of infection-related mortality. No increase in the incidence of ADRs was observed in the VCT group. The use of an individualized antibiotic combination which was selected on the basis of the results ofin vitrocombination testing was associated with significantly lower rates of infection-related mortality in patients with XDR GNB infections. Future prospective randomized studies will be required to validate these findings.

scholarly journals Epidemiology and clinical outcomes associated with extensively drug-resistant (XDR) Acinetobacter in US Veterans’ Affairs (VA) medical centers

2020 ◽  
pp. 1-6
Author(s):  
Margaret A. Fitzpatrick ◽  
Katie J. Suda ◽  
Linda Poggensee ◽  
Amanda Vivo ◽  
Marissa Wirth ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Clinical Outcomes ◽  
Treatment Options ◽  
Patient Characteristics ◽  
Veterans Affairs ◽  
Drug Resistant ◽  
Term Care ◽  
Medical Centers ◽  
Extensively Drug Resistant ◽  
Veterans Affairs Medical Centers

Abstract Objective: Although infections caused by Acinetobacter baumannii are often healthcare-acquired, difficult to treat, and associated with high mortality, epidemiologic data for this organism are limited. We describe the epidemiology, clinical characteristics, and outcomes for patients with extensively drug-resistant Acinetobacter baumannii (XDRAB). Design: Retrospective cohort study Setting: Department of Veterans’ Affairs Medical Centers (VAMCs) Participants: Patients with XDRAB cultures (defined as nonsusceptible to at least 1 agent in all but 2 or fewer classes) at VAMCs between 2012 and 2018. Methods: Microbiology and clinical data was extracted from national VA datasets. We used descriptive statistics to summarize patient characteristics and outcomes and bivariate analyses to compare outcomes by culture source. Results: Among 11,546 patients with 15,364 A. baumannii cultures, 408 (3.5%) patients had 667 (4.3%) XDRAB cultures. Patients with XDRAB were older (mean age, 68 years; SD, 12.2) with median Charlson index 3 (interquartile range, 1–5). Respiratory specimens (n = 244, 36.6%) and urine samples (n = 187, 28%) were the most frequent sources; the greatest proportion of patients were from the South (n = 162, 39.7%). Most patients had had antibiotic exposures (n = 362, 88.7%) and hospital or long-term care admissions (n = 331, 81%) in the prior 90 days. Polymyxins, tigecycline, and minocycline demonstrated the highest susceptibility. Also, 30-day mortality (n = 96, 23.5%) and 1-year mortality (n = 199, 48.8%) were high, with significantly higher mortality in patients with blood cultures. Conclusions: The proportion of Acinetobacter baumannii in the VA that was XDR was low, but treatment options are extremely limited and clinical outcomes were poor. Prevention of healthcare-associated XDRAB infection should remain a priority, and novel antibiotics for XDRAB treatment are urgently needed.

scholarly journals Epidemiology and Clinical Outcomes Associated With Extensively Drug-Resistant (XDR) Acinetobacter in US Veterans’ Affairs Health Care

2020 ◽  
Vol 41 (S1) ◽  
pp. s62-s63
Author(s):  
Margaret Fitzpatrick ◽  
Katie Suda ◽  
Linda Poggensee ◽  
Amanda Vivo ◽  
Marissa Gutkowski ◽  
...  
Keyword(s):  
Health Care ◽  
Cohort Study ◽  
Medical Center ◽  
The United States ◽  
Fourth Generation ◽  
Drug Resistant ◽  
Term Care ◽  
Medical Centers ◽  
Extensively Drug Resistant ◽  
Tract Infections

Background: Infections caused by Acinetobacter spp are often healthcare acquired, difficult to treat, and associated with high mortality. Extensively drug-resistant (XDR) Acinetobacter are nonsusceptible to at least 1 agent in all but 2 or fewer antimicrobial classes. Epidemiologic and outcome data for XDR Acinetobacter are limited and have largely been reported outside the United States. This national cohort study describes epidemiology, clinical characteristics, and outcomes for patients with XDR Acinetobacter in VA health care. Methods: This was a retrospective cohort study including microbiology and clinical data from all patients hospitalized between 2012 and 2018 at any VA medical center who had cultures that grew XDR Acinetobacter spp. Performance and reporting of bacterial speciation and antibiotic susceptibility testing were performed by each VA laboratory according to their protocol. Descriptive statistics were used to summarize data. Results: Of 11,541 unique patients with 15,358 cultures that grew Acinetobacter spp during the study period, 410 (3.6%) patients had 670 (4.4%) cultures that grew XDR Acinetobacter. Mean age was 68 years (SD, 12.2 years) and the median Charlson comorbidity index was 3 (IQR, 1–5). The greatest proportion of isolates were from the respiratory tract (n = 235, 35%) followed by urine (n = 184, 28%). The South had the greatest proportion of patients with XDR Acinetobacter (n = 162, 40%); almost all patients were seen at urban VA medical centers (n = 406, 99%). Most patients (n = 335, 82%) had had antibiotic exposure in the prior 90 days, most commonly vancomycin (n = 238, 65%) and third- or fourth-generation cephalosporins (n = 155, 38%). Most patients (n = 334, 81%) also had a hospital or long-term care admission in the prior 90 days. Fig. 1 shows antibiotic susceptibilities of XDR Acinetobacter isolates; polymyxins, tigecycline, and minocycline demonstrated the highest susceptibility. In-hospital mortality occurred in 90 patients (22%), 30-day mortality in 97 patients (24%), and 1-year mortality in 198 patients (48%). Of 93 patients, 23% were readmitted to the hospital within 90 days. Conclusions: Providers should maintain a heightened suspicion for infection with XDR Acinetobacter spp in older patients seen at urban medical centers who have had recent healthcare and antibiotic exposures, particularly if they have respiratory or urinary tract infections. Isolation of XDR Acinetobacter is associated with high in-hospital and 30-day mortality. New antibiotics targeting MDR gram-negative bacteria generally lack activity against Acinetobacter, leaving polymyxins, tigecycline, and minocycline as the only limited treatment options. Therefore, novel antibiotics for XDR Acinetobacter are urgently needed.Funding: NoneDisclosures: None

scholarly journals Comparison of In Vitro Activity and MIC Distributions between the Novel Oxazolidinone Delpazolid and Linezolid against Multidrug-Resistant and Extensively Drug-Resistant Mycobacterium tuberculosis in China

2018 ◽  
Vol 62 (8) ◽  
Author(s):  
Zhaojing Zong ◽  
Wei Jing ◽  
Jin Shi ◽  
Shu'an Wen ◽  
Tingting Zhang ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Novel Mutation ◽  
Multidrug Resistant ◽  
23S Rrna ◽  
Drug Resistant ◽  
Content Type ◽  
Extensively Drug Resistant ◽  
Significant Difference ◽  
Mdr Tb

ABSTRACT Oxazolidinones are efficacious in treating mycobacterial infections, including tuberculosis (TB) caused by drug-resistant Mycobacterium tuberculosis. In this study, we compared the in vitro activities and MIC distributions of delpazolid, a novel oxazolidinone, and linezolid against multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) in China. Additionally, genetic mutations in 23S rRNA, rplC, and rplD genes were analyzed to reveal potential mechanisms underlying the observed oxazolidinone resistance. A total of 240 M. tuberculosis isolates were included in this study, including 120 MDR-TB isolates and 120 XDR-TB isolates. Overall, linezolid and delpazolid MIC90 values for M. tuberculosis isolates were 0.25 mg/liter and 0.5 mg/liter, respectively. Based on visual inspection, we tentatively set epidemiological cutoff (ECOFF) values for MIC determinations for linezolid and delpazolid at 1.0 mg/liter and 2.0 mg/liter, respectively. Although no significant difference in resistance rates was observed between linezolid and delpazolid among XDR-TB isolates (P > 0.05), statistical analysis revealed a significantly greater proportion of linezolid-resistant isolates than delpazolid-resistant isolates within the MDR-TB group (P = 0.036). Seven (53.85%) of 13 linezolid-resistant isolates were found to harbor mutations within the three target genes. Additionally, 1 isolate exhibited an amino acid substitution (Arg126His) within the protein encoded by rplD that contributed to high-level resistance to linezolid (MIC of >16 mg/liter), compared to a delpazolid MIC of 0.25. In conclusion, in vitro susceptibility testing revealed that delpazolid antibacterial activity was comparable to that of linezolid. A novel mutation within rplD that endowed M. tuberculosis with linezolid, but not delpazolid, resistance was identified.

scholarly journals The Comparison of Hypomethylating Agents (HMA) Monotherapy with HMA Combined with Intensive Chemotherapy for Intermediate / High-Risk MDS or AML

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3903-3903
Author(s):  
Jiang Ji ◽  
Zhao Wang ◽  
Bing Han
Keyword(s):  
High Risk ◽  
Combination Therapy ◽  
Death Rate ◽  
Therapy Group ◽  
Meta Analysis ◽  
Combination Group ◽  
Combination Therapy Group ◽  
Hypomethylating Agents ◽  
Monotherapy Group ◽  
Significant Difference

Introduction: Hypomethylating agents (HMA) azacitidine and decitabine were the first-line therapy for intermediate/ higher-risk myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) patients unsuitable for hematopoietic cell transplantation (HSCT). HMA combined with chemotherapy was recently used to achieve for a better outcome. However, few studies were carried out to compare the HMA monotherapy to the HMA and chemotherapy combination therapy. This meta-analysis aimed to compare the efficacy, survival benefit and safety of HMA monotherapy and combination therapy (with chemotherapy) in patients with intermediate/high-risk MDS or AML. Methods: Related articles published between January 2009 and April 2019 were selected and patients were separated as monotherapy group and combination group for meta-analysis. To further eliminate the potential influence of differences in patients' baseline characteristic between the two groups, subgroups with similar patients' baseline characteristics were selected for further analysis. Complete response (CR) rate, overall response (ORR) rate, 1-year overall survival (OS) rate, 1-month death rate and the proportion of adverse event (AE) were pooled and compared. Results: 13 RCT or cohort studies with 997 patients (790 in monotherapy group, 207 in HMA combination group) were selected for meta-analysis. For the pooled data, there was no significant difference in sex and cytogenetic risk between the 2 groups, but the age of combination therapy group was significantly younger than that of the monotherapy group (61.3±13.2 year-old vs 67.7±10.2 year-old, p=0.000). The CR and ORR rate were significantly higher in combination therapy group (53% vs 17%, p=0.000 for CR and 67% vs 44%, p=0.000 for ORR). However, the 1-year OS (56% for combination therapy vs 51% for HMA monotherapy group, p=0.282) and 1-month death rate (5% for combination therapy vs 4% for HMA monotherapy group, p=0.965) were similar between the two groups. The incidence of CTCAE grade 3-4 infection and bleeding were significantly higher (infection: 50% for combination therapy vs 25.7% for monotherapy group, p=0.003; bleeding: 27.5%% for combination therapy vs 7.8% for monotherapy group, p=0.004) in combination group. In subgroup analysis, 117 and 179 patients were included in combination group and HMA monotherapy group, respectively. There was no significant difference in age (69.5±4.6 vs 69.0±6.8 years old, p=0.451) and proportion of favorable/intermediate cytogenetic risk (62% vs 71%, p=0.114) between the two groups, but a significantly lower proportion of male was found in combination therapy group (57% vs 74%, p=0.003). Although combination group had a higher CR rate (49% vs 17%, p=0.000), it had similar ORR rate (58% vs 49%, p=0.140) to monotherapy group. Meanwhile, combination therapy came with higher 1-month death rate (12% vs 3%, p=0.008) and lower 1-year OS (54% vs 68%, p=0.013) compared with monotherapy group. Conclusions: HMA combined with chemotherapy could increase CR rate in all patients and ORR rate in younger patients, but could not improve OS. For patients with similar older age, combination therapy could result in higher 1-month death rate and less 1-year OS. Disclosures No relevant conflicts of interest to declare.

Intravenous fosfomycin in patients with liver disease for extensively drug-resistant Gram-negative bacteria

2018 ◽  
Vol 77 (5) ◽  
pp. 448-454 ◽  
Author(s):  
Athina Pyrpasopoulou ◽  
Georgia Pitsava ◽  
Elias Iosifidis ◽  
George Imvrios ◽  
Eleni Massa ◽  
...  
Keyword(s):  
Liver Disease ◽  
Gram Negative Bacteria ◽  
Drug Resistant ◽  
Gram Negative ◽  
Extensively Drug Resistant

scholarly journals Intravenous Colistin Monotherapy versus Combination Therapy against Carbapenem-Resistant Gram-Negative Bacteria Infections: Meta-Analysis of Randomized Controlled Trials

2018 ◽  
Vol 7 (8) ◽  
pp. 208 ◽  
Author(s):  
I-Ling Cheng ◽  
Yu-Hung Chen ◽  
Chih-Cheng Lai ◽  
Hung-Jen Tang
Keyword(s):  
Combination Therapy ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Randomized Controlled ◽  
Carbapenem Resistant ◽  
Significant Difference ◽  
All Cause Mortality

This meta-analysis aims to compare intravenous colistin monotherapy and colistin-based combination therapy against carbapenem-resistant gram-negative bacteria (GNB) infections. PubMed, Embase, and Cochrane databases were searched up to July 2018. Only randomized controlled trials (RCTs) evaluating colistin alone and colistin-based combination therapy in the treatment of carbapenem-resistant GNB infections were included. The primary outcome was all-cause mortality. Five RCTs including 791 patients were included. Overall, colistin monotherapy was associated with a risk ratio (RR) of 1.03 (95% confidence interval (CI), 0.89–1.20, I2 = 0%) for all-cause mortality compared with colistin-based combination therapy. The non-significant difference was also detected in infection-related mortality (RR, 1.23, 95% CI, 0.91–1.67, I2 = 0%) and microbiologic response (RR, 0.86, 95% CI, 0.72–1.04, I2 = 62%). In addition, no significant difference was observed in the subgroup analysis—high or low dose, with or without a loading dose, carbapenem-resistant Acinetobacter baumannii infections, and in combination with rifampicin. Finally, colistin monotherapy was not associated with lower nephrotoxicity than colistin combination therapy (RR, 0.98; 95% CI, 0.84–1.21, I2 = 0%). Based on the analysis of the five RCTs, no differences were found between colistin monotherapy and colistin-based combination therapy against carbapenem-resistant GNB infections, especially for A. baumannii infections.

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