Epidemiology and outcomes of multidrug-resistant bacterial infection in non-cystic fibrosis bronchiectasis
Chih-Hao ChangChiung-Hsin ChangShih-Hao HuangChung-Shu LeePo-Chuan KoChun‐Yu LinMeng‐Heng HsiehYu‐Tung HuangHorng‐Chyuan LinLi‐Fu LiFu‐Tsai ChungChun‐Hua WangHung-Yu Huang
5
Citation
36
Reference
10
Related Paper
Citation Trend
Abstract:
Abstract Purpose Multidrug-resistant (MDR) bacteria impose a considerable health-care burden and are associated with bronchiectasis exacerbation. This study investigated the clinical outcomes of adult patients with bronchiectasis following MDR bacterial infection. Methods From the Chang Gung Research Database, we identified patients with bronchiectasis and MDR bacterial infection from 2008 to 2017. The control group comprised patients with bronchiectasis who did not have MDR bacterial infection and were propensity-score matched at a 1:2 ratio. The main outcomes were in-hospital and 3-year mortality. Results In total, 554 patients with both bronchiectasis and MDR bacterial infection were identified. The types of MDR bacteria that most commonly affected the patients were MDR- Acinetobacter baumannii (38.6%) and methicillin-resistant Staphylococcus aureus (18.4%), Extended-spectrum-beta-lactamases (ESBL)- Klebsiella pneumoniae (17.8%), MDR- Pseudomonas (14.8%), and ESBL- E. coli (7.5%). Compared with the control group, the MDR group exhibited lower body mass index scores, higher rate of chronic bacterial colonization, a higher rate of previous exacerbations, and an increased use of antibiotics. Furthermore, the MDR group exhibited a higher rate of respiratory failure during hospitalization (MDR vs. control, 41.3% vs. 12.4%; p < 0.001). The MDR and control groups exhibited in-hospital mortality rates of 26.7% and 7.6%, respectively ( p < 0.001); 3-year respiratory failure rates of 33.5% and 13.5%, respectively ( p < 0.001); and 3-year mortality rates of 73.3% and 41.5%, respectively ( p < 0.001). After adjustments were made for confounding factors, the infection with MDR and MDR bacteria species were determined to be independent risk factors affecting in-hospital and 3-year mortality. Conclusions MDR bacteria were discovered in patients with more severe bronchiectasis and were independently associated with an increased risk of in-hospital and 3-year mortality. Given our findings, we recommend that clinicians identify patients at risk of MDR bacterial infection and follow the principle of antimicrobial stewardship to prevent the emergence of resistant bacteria among patients with bronchiectasis.Keywords:
Acinetobacter baumannii
Colistin
Medical microbiology
Colistin
Acinetobacter baumannii
Cite
Citations (20)
Recent studies have revealed that colistin dependence frequently develops in colistin-susceptible Acinetobacter baumannii isolates. Despite resistance in parental strains, colistin-dependent mutants showed increased susceptibility to several antibiotics, which suggests the possibility of developing strategies to eliminate multidrug-resistant (MDR) A. baumannii. We investigated in vitro and in vivo efficacy of combinations of colistin and other antibiotics using MDR A. baumannii strains H08-391, H06-855, and H09-94, which are colistin-susceptible but develops colistin dependence upon exposure to colistin. An in vitro time-killing assay, a checkerboard assay, and an antibiotic treatment assay using Galleria mellonella larvae were performed. Although a single treatment of colistin at a high concentration did not prevent colistin dependence, combinations of colistin with other antibiotics at subinhibitory concentrations, especially amikacin, eradicated the strains by inhibiting the development of colistin dependence, in the in vitro time-killing assay. Only 40% of G. mellonella larvae infected by A. baumannii survived with colistin treatment alone; however, all or most of them survived following treatment with the combination of colistin and other antibiotics (amikacin, ceftriaxone, and tetracycline). Our results suggest the possibility of the combination of colistin and amikacin or other antibiotics as one of therapeutic options against A. baumannii infections by eliminating colistin-dependent mutants.
Colistin
Acinetobacter baumannii
Amikacin
Cite
Citations (0)
Colistin
Acinetobacter baumannii
Cite
Citations (39)
Colistin
Acinetobacter baumannii
Broth microdilution
Mastoparan
Melittin
Cite
Citations (91)
Adaptation of Acinetobacter baumannii to colistin use on a disease course of a patient was described. Effects of colistin was mimicked in the laboratory conditions. The colistin resistant isolate was identified from the patient after 25 days of colistin treatment. In the laboratory, the expressions of pmrCAB were the highest at the generation which was corresponded to the duration of therapy. A. baumannii can develop a stable colistin-resistant phenotype after three weeks of colistin exposure.
Colistin
Acinetobacter baumannii
Cite
Citations (0)
In this study, we investigated the colistin heteroresistance patterns in Acinetobacter baumannii isolates. To identify colistin heteroresistance, population analysis profiling was performed for six in vitro colistin-susceptible A. baumannii isolates. Survival rates with and without prior exposure to colistin (at concentrations between 0 and 32 mg/L) were measured in media with and without colistin. Amino acid substitutions were also detected in colonies that survived in media with 4 mg/L colistin without further antibiotic treatment in six A. baumannii isolates. A stability test was also performed to investigate whether colistin resistance is maintained without antibiotic treatment. Although only three isolates showed typical colistin heteroresistance pattern, colistin-resistant populations were identified even without prior exposure to colistin in all A. baumannii isolates. Nearly all colonies of typical colistin-heteroresistant isolates (Type I heteroresistance) that survived after exposure to high colistin concentrations were found to be colistin-resistant, whereas no resistant colonies were identified in the other isolates (Type II heteroresistance). Stability tests showed that most of the surviving populations in media with 4 mg/L colistin without further antibiotic exposure failed to preserve resistance to colistin. Colistin-resistant populations also showed either no change in amino acid sequences, or diverse amino acid substitutions. We identified two types of colistin heteroresistance in A. baumannii isolates. Because Type I colistin-heteroresistant A. baumannii isolates could not be eradicated in vitro by high concentrations of colistin, differentiating two colistin heteroresistance types would be important for the treatment of A. baumannii infections using colistin.
Colistin
Acinetobacter baumannii
Cite
Citations (16)
Colistin is the last resort for treatment of multidrug-resistant Acinetobacter baumannii. Unfortunately, resistance to colistin has been reported all over the world. The highest resistance rate was reported in Asia, followed by Europe. The heteroresistance rate of A. baumannii to colistin is generally higher than the resistance rate. The mechanism of resistance might be loss of lipopolysaccharide or/and the PmrAB two-component system. Pharmacokinetic/pharmacodynamic studies revealed that colistin monotherapy is unable to prevent resistance, and combination therapy might be the best antimicrobial strategy against colistin-resistant A. baumannii. Colistin/rifampicin and colistin/carbapenem are the most studied combinations that showed promising results in vitro, in vivo and in the clinic. New peptides showing good activity against colistin-resistant A. baumannii are also being investigated.
Colistin
Acinetobacter baumannii
Carbapenem
Pharmacodynamics
Cite
Citations (533)
Antibiotic resistance has become more and more widespread over the recent decades, becoming a major global health problem and causing colistin to be increasingly used as an antibiotic of last resort. Acinetobacter baumannii, an opportunistic pathogen that has rapidly evolved into a superbug exhibiting multidrug-resistant phenotypes, is responsible for a large number of hospital infection outbreaks. With the intensive use of colistin, A. baumannii resistance to colistin has been found to increase significantly. In previous work, we identified a deflazacort derivative, PYED-1 (pregnadiene-11-hydroxy-16,17-epoxy-3,20-dione-1), which exhibits either direct-acting or synergistic activity against Gram-positive and Gram-negative species and Candida spp., including A. baumannii. The aim of this study was to evaluate the antibacterial activity of PYED-1 in combination with colistin against both A. baumannii planktonic and sessile cells. Furthermore, the cytotoxicity of PYED-1 with and without colistin was assessed. Our results show that PYED-1 and colistin can act synergistically to produce a strong antimicrobial effect against multidrug-resistant populations of A. baumannii. Interestingly, our data reveal that PYED-1 is able to restore the efficacy of colistin against all colistin-resistant A. baumannii isolates. This drug combination could achieve a much stronger antimicrobial effect than colistin while using a much smaller dosage of the drugs, additionally eliminating the toxicity and resistance issues associated with the use of colistin.
Colistin
Acinetobacter baumannii
Polymyxin
Cite
Citations (4)
Multidrug-resistant Acinetobacter baumannii has emerged as a significant clinical problem worldwide and colistin is being used increasingly as "salvage" therapy. MICs of colistin against A. baumannii indicate its significant activity. However, resistance to colistin in A. baumannii has been reported recently. Clonotypes of 16 clinical A. baumannii isolates and ATCC 19606 were determined by pulsed-field gel electrophoresis (PFGE), and colistin MICs were measured. The time-kill kinetics of colistin against A. baumannii ATCC 19606 and clinical isolate 6 were investigated, and population analysis profiles (PAPs) were conducted. Resistance development was investigated by serial passaging with or without exposure to colistin. Five different PFGE banding patterns were found in the clinical isolates. MICs of colistin against all isolates were within 0.25 to 2 microg/ml. Colistin showed early concentration-dependent killing, but bacterial regrowth was observed at 24 h. PAPs revealed that heteroresistance to colistin occurred in 15 of the 16 clinical isolates. Subpopulations (<0.1% from inocula of 10(8) to 10(9) CFU/ml) of ATCC 19606, and most clinical isolates grew in the presence of colistin 3 to 10 microg/ml. Four successive passages of ATCC 19606 in broth containing colistin (up to 200 microg/ml) substantially increased the proportion of the resistant subpopulations able to grow in the presence of colistin at 10 microg/ml from 0.000023 to 100%; even after 16 passages in colistin-free broth, the proportion only decreased to 2.1%. This represents the first demonstration of heterogeneous colistin-resistant A. baumannii in "colistin-susceptible" clinical isolates. Our findings give a strong warning that colistin-resistant A. baumannii may be observed more frequently due to potential suboptimal dosage regimens recommended in the product information of some products of colistin methanesulfonate.
Colistin
Acinetobacter baumannii
Cite
Citations (533)
Acinetobacter baumannii is recognized as a clinically significant pathogen causing a wide spectrum of nosocomial infections. Colistin was considered a last-resort antibiotic for the treatment of infections caused by multidrug-resistant A. baumannii. Since the reintroduction of colistin, a number of mechanisms of colistin resistance in A. baumannii have been reported, including complete loss of LPS by inactivation of the biosynthetic pathway, modifications of target LPS driven by the addition of phosphoethanolamine (PEtN) moieties to lipid A mediated by the chromosomal pmrCAB operon and eptA gene-encoded enzymes or plasmid-encoded mcr genes and efflux of colistin from the cell. In addition to resistance to colistin, widespread heteroresistance is another feature of A. baumannii that leads to colistin treatment failure. This review aims to present a critical assessment of relevant published (>50 experimental papers) up-to-date knowledge on the molecular mechanisms of colistin resistance in A. baumannii with a detailed review of implicated mutations and the global distribution of colistin-resistant strains.
Colistin
Acinetobacter baumannii
Efflux
Cite
Citations (66)