Comparison of colistin–carbapenem, colistin–sulbactam, and colistin plus other antibacterial agents for the treatment of extremely drug-resistant Acinetobacter baumannii bloodstream infections

2014 ◽  
Vol 33 (8) ◽  
pp. 1311-1322 ◽  
Author(s):  
A. Batirel ◽  
I. I. Balkan ◽  
O. Karabay ◽  
C. Agalar ◽  
S. Akalin ◽  
...  
Biomolecules ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 720 ◽  
Author(s):  
Maria Soledad Ramirez ◽  
Robert A. Bonomo ◽  
Marcelo E. Tolmasky

Acinetobacter baumannii is a common cause of serious nosocomial infections. Although community-acquired infections are observed, the vast majority occur in people with preexisting comorbidities. A. baumannii emerged as a problematic pathogen in the 1980s when an increase in virulence, difficulty in treatment due to drug resistance, and opportunities for infection turned it into one of the most important threats to human health. Some of the clinical manifestations of A. baumannii nosocomial infection are pneumonia; bloodstream infections; lower respiratory tract, urinary tract, and wound infections; burn infections; skin and soft tissue infections (including necrotizing fasciitis); meningitis; osteomyelitis; and endocarditis. A. baumannii has an extraordinary genetic plasticity that results in a high capacity to acquire antimicrobial resistance traits. In particular, acquisition of resistance to carbapenems, which are among the antimicrobials of last resort for treatment of multidrug infections, is increasing among A. baumannii strains compounding the problem of nosocomial infections caused by this pathogen. It is not uncommon to find multidrug-resistant (MDR, resistance to at least three classes of antimicrobials), extensively drug-resistant (XDR, MDR plus resistance to carbapenems), and pan-drug-resistant (PDR, XDR plus resistance to polymyxins) nosocomial isolates that are hard to treat with the currently available drugs. In this article we review the acquired resistance to carbapenems by A. baumannii. We describe the enzymes within the OXA, NDM, VIM, IMP, and KPC groups of carbapenemases and the coding genes found in A. baumannii clinical isolates.


Author(s):  
Robert W. Deering ◽  
Kristen E. Whalen ◽  
Ivan Alvarez ◽  
Kathryn Daffinee ◽  
Maya Beganovic ◽  
...  

AbstractThe emergence of multi-drug resistant pathogenic bacteria represents a serious and growing threat to national healthcare systems. Most pressing is an immediate need for the development of novel antibacterial agents to treat Gram-negative multi-drug resistant infections, including the opportunistic, hospital-derived pathogen, Acinetobacter baumannii. Herein we report a naturally occurring 1,2-benzisoxazole with minimum inhibitory concentrations as low as 6.25 μg ml−1 against clinical strains of multi-drug resistant A. baumannii and investigate its possible mechanisms of action. This molecule represents a new chemotype for antibacterial agents against A. baumannii and is easily accessed in two steps via de novo synthesis. In vitro testing of structural analogs suggest that the natural compound may already be optimized for activity against this pathogen. Our results demonstrate that supplementation of 4-hydroxybenzoate in minimal media was able to reverse 1,2-benzisoxazole’s antibacterial effects in A. baumannii. A search of metabolic pathways involving 4-hydroxybenzoate coupled with molecular modeling studies implicates two enzymes, chorismate pyruvate-lyase and 4-hydroxybenzoate octaprenyltransferase, as promising leads for the target of 3,6-dihydroxy-1,2-benzisoxazole.


2020 ◽  
Author(s):  
Jingyi Shi ◽  
Ting Sun ◽  
Yun Cui ◽  
Chunxia Wang ◽  
Fei Wang ◽  
...  

Abstract Background Multidrug resistant (MDR) and extensively drug resistant (XDR) Acinetobacter baumannii presents challenges for clinical treatment and causes high mortality in children. We aimed to assess the risk factors for MDR/XDR Acinetobacter baumannii infection and for overall mortality in this patient population. Methods This retrospective study included 102 pediatric patients who developed MDR/XDR Acinetobacter baumannii infection in the pediatric intensive care unit (PICU) of Shanghai Children’s Hospital in China from December 2014 to May 2018. Clinical presentations and outcome of the patients were analyzed. The primary outcome was overall mortality. Secondary outcomes included the 28-day mortality and the length of hospital stay. Results Of the 102 patients (63 males and 39 females; mean age: 51.79 months), the overall mortality rate was 29.41%. 18(17.64%) had bloodstream infections;4(3.92%) for which cerebrospinal fluid (CSF) cultures were positive; 14(13.73%) of them got positive cultures in aseptic fluid; 10 (9.8%) had central catheter-associated bloodstream infections; lower respiratory isolates (56/102) accounted for 54.9% of all patients. Non-survival patients appeared to have a lower NK cell activity 5.87%(2.43%, 8.93%) vs. 8.45%(4.51%, 14.61%), P =0.011), higher CD4 + T cell ratio (35.32% (29%, 47.81%) vs. 31.97% (20.52%, 38.22%), P = 0.045), and higher serum level of interlukin-6 (IL-6, 235.51(0.1, 4172.77) pg/ml vs. 0.1(0.1, 110.92) pg/ml, P = 0.028), interlukin-8 (IL-8, 22.73(3.14, 540.12) vs. 0.1(0.1, 25.85)pg/ml, P = 0.03) , and interlukin-10(10.82(0.1, 83.29)pg/ml vs. 6.05(0.1,21.81)pg/ml) were observed. Multivariate logistic analysis indicated that high serum level of BUN (RR, 1.216, 95%CI, 1.27-2.616; P = 0.001) and high serum level of Cr (RR, 1.823, 95%CI, 0.902-0.980;P=0.004,) were associated with high risk of overall mortality in MDR/XDR Acinetobacter baumannii infected patients. Conclusion MDR/XDR- Acinetobacter baumannii is an important opportunistic pathogen that causes nosocomial infection in PICU with a rather high mortality. The incidence increased in recent years, ineffective management, immune dysfunction, acute kidney injury contributed to the risk of death.


2019 ◽  
Author(s):  
Jingyi Shi ◽  
Ting Sun ◽  
Yun Cui ◽  
Chunxia Wang ◽  
Fei Wang ◽  
...  

Abstract Background Multiple drug-resistant (MDR) and extensively drug-resistant (XDR) Acinetobacter baumannii presents challenges for clinical treatment and causes high mortality in children. We aimed to assess the risk factors for MDR/XDR Acinetobacter baumannii (MDR/XDR-AB) infection and for 28-day mortality in this patient population.Methods This retrospective study included 102 pediatric patients who developed MDR/XDR-AB infection in the pediatric intensive care unit (PICU) of Shanghai Children’s Hospital in China from January 2015 to December 2017. Clinical presentations and outcome of the patients were analyzed.Results Of the 102 patients (63 males and 39 females; mean age: 51.79 months), There were 63 (61.77%) male in the case group. The 28-day mortality rate was 29.41%. 18(17.64%) had bloodstream infections;4(3.92%) for which cerebrospinal fluid (CSF) cultures were positive; 14(13.73%) of them got positive cultures in aseptic fluid; 10 (9.8%) had central line-associated bloodstream infections; lower respiratory isolates (56/102) accounted for 54.9% of all patients. Multivariate logistic analysis indicated that high serum level of BUN (RR, 1.216, 95%CI, 1.27-2.616; P = 0.001) and high serum level of Cr (RR, 1.823, 95%CI, 0.902-0.980), were associated with high risk of mortality in MDR/XDR-AB infected patients.Conclusion MDR/XDR-Ab infection is a serious concern in pediatric patients with high mortality (29.41%). Mortality rate is higher in blood stream infection and central nervous system infection. Acute kidney injury is associated with high risk of mortality. Early use of tigarecycline might be involved in improving MDR/XDR-AB bacteremia.


Author(s):  
Elham Abbasi ◽  
Hossein Goudarzi ◽  
Ali Hashemi ◽  
Alireza Salimi Chirani ◽  
Abdollah Ardebili ◽  
...  

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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