SciCombinator

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Journal: Antimicrobial agents and chemotherapy

833

The recent discovery of a plasmid-borne colistin resistance gene, mcr-1, heralds the emergence of truly pan-drug resistant bacteria (1).….

Concepts: DNA, Gene, Bacteria, Genome, Antibiotic resistance, Escherichia coli, Plasmid, Proteobacteria

172

Multidrug resistance (MDR) plasmids frequently encode antibiotic resistance genes conferring qualitatively different mechanisms of resistance. We show that the antibiotic concentrations selecting for the RK2 plasmid in Escherichia coli depend upon the sociality of the drug resistance: Selection for a selfish drug resistance (efflux-pump) occurred at very low drug concentrations, just 1.3% of the sensitive’s MIC, whereas selection for a cooperative drug resistance (modifying-enzyme) occurred at drug concentrations exceeding the MIC of the plasmid-free strain.

Concepts: Gene, Natural selection, Bacteria, Genome, Antibiotic resistance, Escherichia coli, Plasmid, Bacterial conjugation

169

Pathogenic Leptospira spp., the causative agents of leptospirosis, are slow-growing Gram-negative spirochetes. Isolation of Leptospira from clinical samples and testing of antimicrobial susceptibility are difficult and time-consuming. Here, we describe the development of a new solid medium that facilitates more-rapid growth of Leptospira spp. and the use of this medium to evaluate the Etest’s performance in determining antimicrobial MICs to drugs in common use for leptospirosis. The medium was developed by evaluating the effects of numerous factors on the growth rate of Leptospira interrogans strain NR-20157. These included the type of base agar, the concentration of rabbit serum (RS), and the concentration and duration of CO(2) incubation during the initial period of culture. The highest growth rate of NR-20157 was achieved using a Noble agar base supplemented with 10% RS (named LVW agar), with an initial incubation at 30°C in 5% CO(2) for 2 days prior to continuous culture in air at 30°C. These conditions were used to develop the Etest for three species, L. interrogans (NR-20161), L. kirschnerii (NR-20327), and L. borgpetersenii (NR-20151). The MICs were read on day 7 for all samples. The Etest was then performed on 109 isolates of pathogenic Leptospira spp. The MIC(90) values for penicillin G, doxycycline, cefotaxime, ceftriaxone, and chloramphenicol were 0.64 units/ml and 0.19, 0.047, 0.5, and 2 μg/ml, respectively. The use of LVW agar, which enables rapid growth, isolation of single colonies, and simple antimicrobial susceptibility testing for Leptospira spp., provides an opportunity for new areas of fundamental and applied research.

Concepts: Microbiology, Penicillin, Spirochaetes, Spirochaete, Leptospira, Leptospirosis, The Medium, Causative

164

For its remarkable ability to acquire antibiotic resistance and to survive in nosocomial environments, Acinetobacter baumannii has become a significant nosocomial infectious agent worldwide. Tigecycline is one of the few therapeutic options to treat infections caused by A. baumannii isolates. However, tigecycline resistance has been increasingly reported. Our aim was to assess the prevalence and characteristics of efflux-based tigecycline resistance in clinical isolates of A. baumannii collected from a hospital in China. A total of 74 A. baumannii isolates including 64 tigecycline non-susceptible A. baumannii (TNAB) and 10 tigecycline susceptible A. baumannii (TSAB) isolates were analyzed. The majority of them were detected to be positive for adeABC, adeRS, adeIJK and abeM, while the adeE gene was found in only one TSAB isolate. Compared with TSAB isolates, the mean expression level of adeB, adeJ, adeG and abeM in TNAB isolates were observed to increase by 29-, 3-, 0.7- and 1-fold, respectively. The efflux pump inhibitors (EPIs) PAβN and carbonyl cyanide 3-chlorophenylhydrazone (CCCP) could partially reverse the resistance pattern of tigecycline. Moreover, tetX1 gene was detected in 12 (18.8%) TNAB isolates. To our knowledge, this is the first report that tetX1 gene was detected in the A. baumannii isolates. ST208 and ST191 which both clustered into clonal complex 92 (CC92) were the predominant sequence types (STs). This study showed that active efflux pump AdeABC appeared to play important roles in the tigecycline resistance of A. baumannii. The dissemination of TNAB isolates in our hospital is mainly attributable to the spread of CC92.

Concepts: Nosocomial infection, Antibiotic resistance, Antibiotic, Pseudomonadales, Acinetobacter baumannii, Acinetobacter, Tigecycline, Efflux

132

We present case histories of four patients treated with artemether-lumefantrine for falciparum malaria in UK hospitals in 2015-16. Each subsequently presented with recurrent symptoms and Plasmodium falciparum parasitaemia within 6 weeks of treatment with no intervening travel to malarious countries. Parasite isolates, all of African origin, harboured variants at some candidate resistance loci. No evidence of pfk13-mediated artemisinin resistance was found. Vigilance for signs of unsatisfactory antimalarial efficacy among imported cases of malaria is recommended.

Concepts: Malaria, Plasmodium falciparum, Plasmodium, Plasmodium vivax, Anopheles, Quinine, Apicomplexa, Artemisinin

77

54

Widespread antibiotic use in clinical medicine and the livestock industry has contributed to the global spread of multidrug-resistant (MDR) bacterial pathogens, including Acinetobacter baumannii We report on a method used to produce a personalized bacteriophage-based therapeutic treatment for a 68-year old diabetic patient with necrotizing pancreatitis complicated by a MDR A. baumannii infection. Despite multiple antibiotic courses and efforts at percutaneous drainage of a pancreatic pseudocyst, the patient deteriorated over a four-month period. In the absence of effective antibiotics, two laboratories identified nine different bacteriophages with lytic activity for an A. baumannii isolate from the patient. Administration of these bacteriophages intravenously and percutaneously into the abscess cavities was associated with reversal of the patient’s downward clinical trajectory, clearance of the A. baumannii infection, and a return to health. The outcome of this case suggests that the methods described here for the production of bacteriophage therapeutics could be applied to similar cases and that more concerted efforts to investigate the use of therapeutic bacteriophages for MDR bacterial infections are warranted.

Concepts: Inflammation, Medicine, Bacteria, Microbiology, Virus, Antibiotic resistance, Phage therapy, Acinetobacter baumannii

43

Neisseria gonorrhoeae is one of the leading antimicrobial resistance threats worldwide. This study determined the minimum inhibitory concentrations of closthioamide to be 0.008-0.5 mg/L for clinical N. gonorrhoeae strains and related species. Cross-resistance with existing antimicrobial resistance was not detected, indicating that closthioamide could be used to treat drug-resistant N. gonorrhoeae.

Concepts: Antibiotic resistance, In vitro fertilisation, In vitro, Proteobacteria, Neisseria gonorrhoeae, Neisseria, Gonorrhea, Drug resistance

42

Among 390 Escherichia coli and Klebsiella pneumoniae clinical isolates collected during 2014-2015 displaying colistin MIC values ≥4 μg/ml, 19 (4.9%) carried mcr-1 These isolates were all E. coli collected in ten countries, including the United States. Most isolates were susceptible to cephalosporins and were all susceptible to carbapenems, amikacin, tigecyline and ceftazidime-avibactam among other agents. Data from this global surveillance program expand the knowledge on the occurrence of mcr-1-carrying isolates.

Concepts: United States, Escherichia coli, Enterobacteriaceae, Escherichia, Proteobacteria, Beta-lactamase, Enterobacteria, Cephalosporin

40

Antibiotic use is the main driver in the emergence of antibiotic resistance. Another unexplored possibility is that resistance evolves coincidentally in response to other selective pressures. We show that selection in the absence of antibiotics can co-select for decreased susceptibility to several antibiotics. Thus, genetic adaptation of bacteria to natural environments may drive resistance evolution by generating a pool of resistance mutations that selection could act on to enrich resistant mutants when antibiotic exposure occurs.

Concepts: Gene, Genetics, Natural selection, Bacteria, Evolution, Virus, Antibiotic resistance, Antibiotic