Efficacy of monotherapy and combined antibiotic therapy for carbapenem-resistant Acinetobacter baumannii pneumonia in an immunosuppressed mouse model

2009 ◽  
Vol 33 (1) ◽  
pp. 33-39 ◽  
Author(s):  
Joon Young Song ◽  
Hee Jin Cheong ◽  
Jacob Lee ◽  
Ah Kyeong Sung ◽  
Woo Joo Kim
Keyword(s):  
Mouse Model ◽  
Antibiotic Therapy ◽  
Acinetobacter Baumannii ◽  
Carbapenem Resistant ◽  
Immunosuppressed Mouse

scholarly journals In vivo efficacy of combination of colistin with fosfomycin or minocycline in a mouse model of multidrug-resistant Acinetobacter baumannii pneumonia

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Nam Su Ku ◽  
Su-Hyung Lee ◽  
Young- soun Lim ◽  
Heun Choi ◽  
Jin Young Ahn ◽  
...  
Keyword(s):  
Mouse Model ◽  
Acinetobacter Baumannii ◽  
Synergistic Effects ◽  
Bacterial Load ◽  
Multidrug Resistant ◽  
Therapeutic Options ◽  
Severance Hospital ◽  
Carbapenem Resistant ◽  
Combination Regimens

AbstractUnfortunately, the options for treating multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii) infections are extremely limited. Recently, fosfomycin and minocycline were newly introduced as a treatment option for MDR A. baumannii infection. Therefore, we investigated the efficacy of the combination of colistin with fosfomycin and minocycline, respectively, as therapeutic options in MDR A. baumannii pneumonia. We examined a carbapenem-resistant A. baumannii isolated from clinical specimens at Severance Hospital, Seoul, Korea. The effect of colistin with fosfomycin, and colistin with minocycline on the bacterial counts in lung tissue was investigated in a mouse model of pneumonia caused by MDR A. baumannii. In vivo, colistin with fosfomycin or minocycline significantly (p < 0.05) reduced the bacterial load in the lungs compared with the controls at 24 and 48 h. In the combination groups, the bacterial loads differed significantly (p < 0.05) from that with the more active antimicrobial alone. Moreover, the combination regimens of colistin with fosfomycin and colistin with minocycline showed bactericidal and synergistic effects compared with the more active antimicrobial alone at 24 and 48 h. This study demonstrated the synergistic effects of combination regimens of colistin with fosfomycin and minocycline, respectively, as therapeutic options in pneumonia caused by MDR A. baumannii.

scholarly journals Piscidin is Highly Active against Carbapenem-Resistant Acinetobacter baumannii and NDM-1-Producing Klebsiella pneumonia in a Systemic Septicaemia Infection Mouse Model

Marine Drugs ◽  
2015 ◽  
Vol 13 (4) ◽  
pp. 2287-2305 ◽  
Author(s):  
Chieh-Yu Pan ◽  
Jian-Chyi Chen ◽  
Te-Li Chen ◽  
Jen-Leih Wu ◽  
Cho-Fat Hui ◽  
...  
Keyword(s):  
Mouse Model ◽  
Acinetobacter Baumannii ◽  
Klebsiella Pneumonia ◽  
Highly Active ◽  
Carbapenem Resistant

scholarly journals 523. Dual vs. Triple Antibiotic Therapy for Carbapenem-Resistant Acinetobacter baumannii Infections

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S252-S252
Author(s):  
Justin Patrick Markelwith ◽  
Nikunj M Vyas ◽  
Mark Condoluci ◽  
Sungwook Kim
Keyword(s):  
Combination Therapy ◽  
Serum Creatinine ◽  
Antibiotic Therapy ◽  
Acinetobacter Baumannii ◽  
Clinical Cure ◽  
Group Analysis ◽  
Elevated Serum ◽  
Positive Association ◽  
Primary Analysis ◽  
Carbapenem Resistant

Abstract Background Infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB) remain some of the most difficult to treat due to extremely high rates of resistance. The purpose of this study was to compare the efficacy of dual vs. triple targeted antibiotic regimens for CRAB infections. Methods This was an IRB approved retrospective cohort study performed at a 607-bed community health system between January 2016 and December 2018. Patients were included in the analysis if they were ≥18 years old and received antibiotics for CRAB for ≥72 hours. Patients were excluded if they were pregnant and had CRAB isolated solely from the urine. The primary endpoints of the study were differences in all-cause in-hospital mortality (ACIM) and clinical cure (CC) rates for patients treated with dual vs. triple antibiotic therapy. The secondary endpoint result focused on the difference in length of stay (LOS) between treatment groups. A sub-group analysis was performed for patients treated with tigecycline vs. minocycline combination therapy to determine differences ACIM and CC, and LOS. A multi-logistic regression analysis (MLRA) was performed to determine patient factors that were associated with ACIM and CC. Results A total of 32 patients were included in the primary analysis. No difference was seen in ACIM between dual vs. triple antibiotic groups (9.5% vs. 18.2%, P = 0.59). CC (63.6% vs. 57.1%, P = 1.0) and LOS (12 vs. 11 days, P = 1.0) was similar amongst patients treated with dual vs. triple antibiotic group. No differences were seen in ACIM (15.4% vs. 16.7% P = 1.0), CC (83.3% vs. 69.2%, P = 1.0) and LOS (15 vs. 14 days, P = 1.0) between tigecycline and minocycline combination therapy groups. The MLRA revealed a positive association with increased serum creatinine and ACIM (OR 3.29, 95% CI 1.35–8.04; P = 0.009) as well as shorter time to appropriate antibiotic therapy and clinical cure (OR 1.49, 95% CI 1.02–2.20; P = 0.04). CRAB isolates were more likely to be susceptible to minocycline vs. tigecycline (83% vs. 18%, P = 0.003). Conclusion No differences were seen in ACIM, CC and LOS between dual vs. triple antibiotic groups. Minocycline tends to sustain better susceptibility toward CRAB vs. tigecycline. Elevated serum creatinine was found to be a predictor for ACIM while shorter time to appropriate antibiotic therapy was associated with CC. Disclosures All authors: No reported disclosures.

Do Results of Surveillance Cultures Impact the Choice of Empirical Antibiotics Among Patients with Carbapenem-Resistant Acinetobacter baumannii Infections?

2015 ◽  
Vol 36 (12) ◽  
pp. 1455-1457
Author(s):  
Rossana Rosa ◽  
Jose Castro ◽  
Rachel Latibeaudiere ◽  
Nicholas Namias ◽  
L. Silvia Munoz-Price
Keyword(s):  
Antibiotic Therapy ◽  
Acinetobacter Baumannii ◽  
Infect Control Hosp ◽  
Empirical Antibiotic Therapy ◽  
Carbapenem Resistant ◽  
Surveillance Cultures ◽  
Empirical Antibiotics

We aimed to determine whether the results of surveillance cultures were associated with use of appropriate empirical antibiotic therapy among patients with carbapenem-resistant Acinetobacter baumannii infections. We found that surveillance status was not associated with appropriate empirical antibiotic therapy (P=.36). There were significant delays to concordant therapy among surveillance-positive patients (P=.03).Infect. Control Hosp. Epidemiol. 2015;36(12):1455–1457

scholarly journals Lyb-2-4, a unique genomic region of hypervirulent carbapenem-resistant Acinetobacter baumannii

2019 ◽  
Author(s):  
Chao Zheng ◽  
Jinyong Zhang ◽  
Min Zhang ◽  
Zhou Liu ◽  
Yuxin Zhong ◽  
...  
Keyword(s):  
Mouse Model ◽  
Acinetobacter Baumannii ◽  
Multilocus Sequence Typing ◽  
Core Genome ◽  
Medical Intervention ◽  
Genomic Region ◽  
Multi Drug Resistance ◽  
Comparative Genomic ◽  
Low Grade ◽  
Carbapenem Resistant

ABSTRACTAcinetobacter baumannii is an important human pathogen due to its multi-drug resistance, but is usually with low-grade virulence. Although a mouse model revealed different virulence grades of clinical carbapenem-resistant A. baumannii (CRAB) strains, the genetic basis remains unknown. We collected 61 CRAB isolates from intensive care unit of Shenzhen People’s Hospital (Shenzhen, China), and analyzed them used whole genome sequencing (WGS), multilocus sequence typing (MLST) and core genome MLST (cgMLST), transmission chain reconstruction and Comparative genomic tools. A mouse pneumonia model was used to confirm the hypervirulent phenotype. Eleven complex types (CT) were identified based on core genome multilocus sequence typing scheme. CT512 showed higher transmissibility and bloodstream infection rates than other CTs. A genomic region Lyb-2-4 was shared by CT512 and CT2092 but not CT2085. The mortality rates of patient infected with CRAB harboring Lyb-2-4 was significantly higher than those infected with CRAB isolates without Lyb-2-4 (77.8% vs 24.5%, p < 0.01). In the mouse model, the survival rates of strains containing the Lyb-2-4 region (LAC-4, 5122 and 2092) were significantly lower than for strains without Lyb-2-4 (7152, 71517, 20859 and ATCC17978). One open reading frame (ORF) was a marker for the presence of Lyb-2-4, and PCR of a segment of this ORF, designated as hvcT, served as a tag for hypervirulent CRAB. Our study should be very useful in advising the clinician to implement medical intervention earlier, and also making the worldwide surveillance of these hypervirulent CRAB strains easier.IMPORTANCEHypervirulent CRAB strains are expected to pose a threat to human health because infection of these strains is associated with high mortality and multidrug resistance. The rapid hypervirulent CRAB identification assay will facilitate prompt medical intervention. Our findings should provoke surveillance for hypervirulent CRAB strains harboring Lyb-2-4 in other countries. Further research should focus on the mechanism of hypervirulence, the acquisition of this genomic region and the development of control measures to prevent further dissemination.

scholarly journals 842. Impact of Active Treatment of Carbapenem-Resistant Acinetobacter baumannii Infections in US Hospitals Between 2014 and 2019

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S462-S462
Author(s):  
Jason M Pogue ◽  
Yun Zhou ◽  
Hemanth Kanakamedala ◽  
Bin Cai
Keyword(s):  
Antibiotic Therapy ◽  
Acinetobacter Baumannii ◽  
Active Treatment ◽  
Panel Member ◽  
Readmission Rates ◽  
Independent Contractor ◽  
In Vitro Susceptibility ◽  
Carbapenem Resistant ◽  
Discharge Status ◽  
The Impact

Abstract Background Treatment choices for carbapenem-resistant (CR) Acinetobacter baumannii infections are limited. We analyzed the impact of active treatment on outcomes in patients infected with CR vs carbapenem-susceptible (CS) A. baumannii. Methods Adult patients hospitalized between January 1, 2014 and June 30, 2019 with A. baumannii infections recorded in the Premier Database were retrospectively evaluated. Outcomes including mortality, discharge status (home vs other), and readmission rates were calculated as a function of receipt of active antibiotic treatment, infection site, and CR status. Antibiotic therapy was considered active if given after the index culture and displaying in vitro susceptibility. Results Among 3,500 patients with A. baumannii (CR n=1,608; CS n=1,892), 2,057 patients (58.8%) received active treatment, with a much lower proportion of CR A. baumannii patients receiving active treatment than CS patients (606 [37.7%] vs 1,451 [76.7%]). Patients without active treatment had similar rates of in-hospital mortality (14.3% vs 12.9%, P=0.25) but were less likely to be discharged to home (26.3% vs 37.0%, P&lt; 0.001) than those that received active treatment. No association between receipt of active treatment and overall mortality or discharged status was demonstrated for CR isolates (Table 1). However, among the subset of patients with CR bloodstream infections, mortality was higher in those without active treatment compared to those with active treatment (55.1% vs 25.9%, P=0.009). Overall readmission rates due to A. baumannii were considerably higher for those who did not receive active treatment vs those who did (16.0% vs 7.5%, P&lt; 0.001) and the same was seen by differing infection sites; primarily driven by CR patients with bloodstream, respiratory, or urine infections (Table 2). Table 1. Mortality and discharge status by active treatment and carbapenem susceptibility Table 2. Readmission due to A. baumannii by active treatment and CR status among patients discharged alive Conclusion Active antibiotic therapy was associated with improved outcomes in patients with A. baumannii infections, although perhaps not to the extent expected. Further investigation into the impact of active therapy on outcomes is warranted. Disclosures Jason M Pogue, PharmD, BCPS, BCIDP, Shionogi Inc. (Advisor or Review Panel member) Yun Zhou, MS, Shionogi Inc. (Independent Contractor) Hemanth Kanakamedala, BS, Shionogi Inc. (Independent Contractor) Bin Cai, MD, PhD, Shionogi Inc. (Employee)

Decreased carO gene expression and OXA-type carbapenemases among extensively drug-resistant Acinetobacter baumannii strains isolated from burn patients in Tehran, Iran

2020 ◽  
Author(s):  
Elham Abbasi ◽  
Hossein Goudarzi ◽  
Ali Hashemi ◽  
Alireza Salimi Chirani ◽  
Abdollah Ardebili ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acinetobacter Baumannii ◽  
High Rate ◽  
Burn Patients ◽  
Drug Resistant ◽  
Disc Diffusion ◽  
Carbapenem Resistant ◽  
Extensively Drug Resistant ◽  
Sds Page ◽  
Extensively Drug Resistance

AbstractA major challenge in the treatment of infections has been the rise of extensively drug resistance (XDR) and multidrug resistance (MDR) in Acinetobacter baumannii. The goals of this study were to determine the pattern of antimicrobial susceptibility, blaOXA and carO genes among burn-isolated A. baumannii strains. In this study, 100 A. baumannii strains were isolated from burn patients and their susceptibilities to different antibiotics were determined using disc diffusion testing and broth microdilution. Presence of carO gene and OXA-type carbapenemase genes was tested by PCR and sequencing. SDS-PAGE was done to survey CarO porin and the expression level of carO gene was evaluated by Real-Time PCR. A high rate of resistance to meropenem (98%), imipenem (98%) and doripenem (98%) was detected. All tested A. baumannii strains were susceptible to colistin. The results indicated that 84.9% were XDR and 97.9% of strains were MDR. In addition, all strains bore blaOXA-51 like and blaOXA-23 like and carO genes. Nonetheless, blaOXA-58 like and blaOXA-24 like genes were harbored by 0 percent and 76 percent of strains, respectively. The relative expression levels of the carO gene ranged from 0.06 to 35.01 fold lower than that of carbapenem-susceptible A. baumannii ATCC19606 and SDS – PAGE analysis of the outer membrane protein showed that all 100 isolates produced CarO. The results of current study revealed prevalence of blaOXA genes and changes in carO gene expression in carbapenem resistant A.baumannii.

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