- Mycobacterium abscessus Complex Infections: A Retrospective Cohort Study. [Journal Article]
- OFOpen Forum Infect Dis 2018; 5(2):ofy022
- CONCLUSIONS: Our cohort of 108M. abscessuscomplex isolates in Miami, Florida, showed an in-hospital mortality of 15.7%. Most infections were respiratory. Clarithromycin and amikacin were the most likely agents to be susceptible in vitro. Resistance to fluoroquinolone and trimethoprim/sulfamethoxazole was highly common. Macrolide resistance, immunosuppression, and renal disease were significantly associated with early treatment failure.
- Establishment and validation ofGalleria mellonellaas a novel model organism to studyMycobacterium abscessusinfection, pathogenesis and treatment. [Journal Article]
- AAAntimicrob Agents Chemother 2018 Feb 05
- Introduction: Treatment ofMycobacterium abscessusinfections is extremely challenging due to its intrinsic resistance to most antibiotics, and research of pathogenesis is limited d...
Introduction: Treatment ofMycobacterium abscessusinfections is extremely challenging due to its intrinsic resistance to most antibiotics, and research of pathogenesis is limited due to a lack of a practicalin vivomodel of infection.Objectives: To establish a simplein-vivomodel forM. abscessusinfection, virulence, and drug testing inG. mellonellalarvae.Methods: We inoculated larvae withM. abscessus, and followed histopathology, CFU count and mortality with and without antibiotic treatment. We also constructed a luminescent, recombinantM. abscesssus, mDB158, and imaged infected larvae using IVIS®.Results:M. abscessusproliferated and induced granulomatous-like responses in infected larvae leading to larval mortality. TheG. mellonellamodel was further successfully validated by demonstration of the expected favorable antimicrobial effect of treatment with meropenem, and the superiority of combination treatment (meropenem and tigecycline) over single agents. We then used IVIS® imaging of larvae infected with luminescentM. abscessus, allowing live real-time assessment of bacterial load. We used this method to compare the antimicrobial effect of various antibiotics (meropemen, amikacin, linezolid, levofloxacin, etc.) on bacterial proliferation and larval survival. Meropenem and amikacin had the most favorable effect, correlating well with common clinical practice guidelines.Conclusions: These findings suggestG. mellonellato be an excellentin vivomodel for research ofM. abscessusinfection, pathogenesis and treatment. LuminescentM. abscessusand IVIS® imaging further facilitates this model. Results obtained in this model clearly substantiated common clinical practice, thus validating the model as a predictor of treatment efficacy and outcome.
- Drug susceptibility profiling and genetic determinants of drug resistance inMycobacterium kansasii. [Journal Article]
- AAAntimicrob Agents Chemother 2018 Feb 05
- Studies on drug susceptibility ofMycobacterium kansasiiare very few and involve limited number of strains. The purpose of this study was to determine drug susceptibility profiles ofM. kansasiiisolate...
Studies on drug susceptibility ofMycobacterium kansasiiare very few and involve limited number of strains. The purpose of this study was to determine drug susceptibility profiles ofM. kansasiiisolates representing a spectrum of species genotypes (subtypes) with two different methodologies, i.e. broth microdilution and E-test assays. To confirm drug resistance, drug target genes were sequenced.A collection of 85M. kansasiiisolates, including representatives of eight different subtypes (I-VI, I/II, IIB) from eight countries was used. Drug susceptibility against 13 and 8 anti-mycobacterial agents was tested by using broth microdilution and E-test method, respectively. For drug-resistant or high-MIC isolates, eight structural genes (rrl,katG,inhA,embB,rrs,rpsL,gyrA, andgyrB) and one regulatory region (embCA) were PCR-amplified and sequenced in the search for resistance-associated mutations.All isolates tested were susceptible to rifampicin (RIF), amikacin (AMK), co-trimoxazole (SXT), rifabutin (RFB), moxifloxacin (MXF), and linezolid (LZD), when using microdilution method. Resistance to ethambutol (EMB), ciprofloxacin (CIP), and clarithromycin (CLR) was found in 83 (97.7%), 17 (20%), and 1 (1.2%) isolate, respectively. The calculated concordance between the E-test and dilution method was 22.6% for AMK, 4.8% for streptomycin (STR), 3.2% for CLR, and 1.6% for RIF. For EMB, INH, and SXT, not even a single MIC value determined by one method equaled that by the second method. The only mutations disclosed were A2266C transversion atrrlgene (CLR-resistant strain) and A128G transition atrpsLgene (strain with STR MIC >64 mg/L).In conclusion, eight drugs, including RIF, CLR, AMK, SXT, RFB, MXF, LZD, and ethionamide (ETO) showed highin vitroactivity againstM. kansasiiisolates. Discrepancies of the results between the reference microdilution method and E-test precludes the use of the latter for drug susceptibility determination inM. kansasiiDrug resistance inM. kansasiimay have different genetic determinants than resistance to the same drugs inM. tuberculosis.
- Genetic characterization and in vitro activity of antimicrobial combinations of multidrug-resistant Acinetobacter baumannii from a general hospital in China. [Journal Article]
- OLOncol Lett 2018; 15(2):2305-2315
- The present study aimed to develop a rational therapy based on the genetic epidemiology, molecular mechanism evaluation and in vitro antibiotic combinations activity in multidrug-resistant Acinetobac...
The present study aimed to develop a rational therapy based on the genetic epidemiology, molecular mechanism evaluation and in vitro antibiotic combinations activity in multidrug-resistant Acinetobacter baumannii (MDRAB). MDRAB was screened by the Kirby-Bauer method. The random amplified polymorphic DNA technique was used to establish genetic fingerprinting, and a series of resistance genes were detected by polymerase chain reaction. Antimicrobial agents including amikacin (AK), cefoperazone/sulbactam (SCF I/II), meropenem (MEM), minocycline (MINO) and ciprofloxacin (CIP) were used to determine the minimum inhibitory concentrations (MICs) and interactions between antibiotics by the broth microdilution method and chequerboard assays. In total, 34 MDRAB strains were isolated and classified into 8 phenotypes A-H, according to their general drug susceptibilities. A total of 4 major genotypes (I-IV) were clustered at 60% a genotypic similarity threshold. High positive rates of β-lactamase TEM-1, topoisomerase IV, oxacillinase (OXA)-23, AdeB family multidrug efflux RND transporter adeB, β-lactamase AmpC, class 1 integrons (Int-1), 16S rRNA methylase rmtA, phosphotransferase aph(3), 16S rRNA methyltransferase armA were presented to exceed 90%, acetylyltransferase aac(3)-I, aac(6'-I, ant(3″)-I, 16S rRNA methylase rmtB, oxacillinase OXA-24 and metallo-β-lactamase IMP-5 genes demonstrated positive rates of 29.4-85.29%, while adeRS two-component system was not observed in any strain. MEM+SCF I or SCF II primarily exhibited synergistic effects. AK+SCF I, AK+SCF II, MINO+SCF I, MINO+SCF II, MINO+CIP and MINO+MEM primarily presented additive effects. AK+CIP demonstrated 70.59% antagonism. The antibacterial activity of SCF I was superior compared with that of SCF II. The results indicated the polyclonal genetic epidemiological trend of MDRAB in the Second Xiangya Hospital, and verified the complexity of genetic resistance. In addition, combinations suggested to be efficacious were MEM+SCF I and MEM+SCF II, which were more effective compared with other combinations for the management of MDRAB infection.
- In vitro activities of carbapenems in combination with amikacin, colistin, or fosfomycin against carbapenem-resistant Acinetobacter baumannii clinical isolates. [Journal Article]
- DMDiagn Microbiol Infect Dis 2018 Jan 31
- Carbapenem-resistant Acinetobacter baumannii clinical isolates (n=23) were investigated for carbapenem resistance mechanisms and in vitro activities of carbapenems in combination with amikacin, colis...
Carbapenem-resistant Acinetobacter baumannii clinical isolates (n=23) were investigated for carbapenem resistance mechanisms and in vitro activities of carbapenems in combination with amikacin, colistin, or fosfomycin. Major carbapenem resistance mechanism was OXA-23 production. The vast majority of these isolates were OXA-23-producing A. baumannii ST195 and ST542, followed by novel STs, ST1417, and ST1423. The interuption of carO by a novel insertion sequence, ISAba40, was found in two isolates. The combinations of imipenem and fosfomycin, meropenem and amikacin, imipenem and amikacin, and imipenem and colistin were synergistic against carbapenem-resistant A. baumannii by 65.2%, 46.2%, 30.8%, and 17.4%, respectively. Surprisingly, the combination of imipenem and fosfomycin was the most effective in this study against A. baumannii, which is intrinsically resistant to fosfomycin. Imipenem and fosfomycin inhibit cell wall synthesis; therefore, fosfomycin may be an adjuvant and enhance the inhibition of cell wall synthesis of carbapenem-resistant A. baumannii when combined with imipenem.
- Synergism of prenylflavonoids from Morus alba root bark against clinical MRSA isolates. [Journal Article]
- PPhytomedicine 2018 Jan 15; 39:93-99
- CONCLUSIONS: The study revealed for the first time the anti-MRSA synergism of prenylflavonoids 1-4 with eleven antibacterial agents and the reversal of MRSA resistance to aminoglycosides, especially amikacin. The results might be valuable for the development of new antibacterial drugs and synergists against MRSA infection.
- The frequency of Klebsiella pneumonia encoding genes for CTX-M, TEM-1 and SHV-1 extended-spectrum beta lactamases enzymes isolated from urinary tract infection. [Journal Article]
- ACAnn Clin Microbiol Antimicrob 2018 Feb 13; 17(1):4
- CONCLUSIONS: This study showed that K. pneumonia isolated from urine producing β-lactamase were resistance to a wide range of antibiotics. Due to the increasing resistance of most antibiotics, control and supervision in the use of antibiotics and identification of broad spectrum β-lactamase enzymes by phenotypic methods appears to be essential.
- [Burkholderia cepacia infection in children: a clinical analysis of 16 cases]. [Journal Article]
- ZDZhongguo Dang Dai Er Ke Za Zhi 2018; 20(2):112-115
- CONCLUSIONS: Burkholderia cepacia is an opportunistic pathogen often found in immunocompromised children and can produce drug resistance. The presence or absence of underlying diseases should be considered during anti-infective therapy. The children with Burkholderia cepacia infection often have a poor prognosis, and an understanding of the disease spectrum of Burkholderia cepacia infection helps with clinical diagnosis and treatment.
- Effect of extended infusion of meropenem and nebulized amikacin on Gram-negative multidrug-resistant ventilator-associated pneumonia. [Journal Article]
- SJSaudi J Anaesth 2018 Jan-Mar; 12(1):89-94
- CONCLUSIONS: Adding nebulized amikacin to systemic antibiotics in patients with VAP caused by Gram-negative MDRO may offer efficacy benefits, and the use of extended infusions of meropenem could improve the clinical outcomes in critically ill populations.
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- In vitro activity of minocycline combined with aminoglycosides against Klebsiella pneumoniae carbapenemase-producing K. pneumoniae. [Journal Article]
- JAJ Antibiot (Tokyo) 2018 Feb 07
- This study assessed the in vitro antibacterial activity of minocycline-aminoglycoside combination against Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae. Seventy non-duplicate clin...
This study assessed the in vitro antibacterial activity of minocycline-aminoglycoside combination against Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae. Seventy non-duplicate clinical isolates of KPC-producing K. pneumoniae were collected from patients with bloodstream infections. The synergistic activity of minocycline-aminoglycoside combination was studied by the checkerboard method and time-kill assays in strains with different susceptibilities, and the mutant prevention concentration (MPC) and mutant selection window (MSW) of drugs alone and in combination were determined. The checkerboard method found this combination displayed synergistic and partial synergistic activity against aminoglycoside-susceptible isolates, but indifferent activity against aminoglycoside-resistant isolates. Time-kill assays further demonstrated strong synergistic and bactericidal effect of this combination existed against isolates which were susceptible to both drugs. But for resistant isolates, the time-kill assays showed no synergy. The MPCs of minocycline or aminoglycosides were 8- to 32-fold higher than the MICs, suggesting the MSWs of these drugs were quite wide. For the antibiotic combinations, the addition of 1×MIC concentration of amikacin or gentamicin could reduce the MPCs of minocycline by 4- to 16-fold. Generally, no mutants recovered in the plates containing 1×MIC concentration of minocycline and 2×MIC concentration of amikacin or gentamicin. In summary, these results suggest that minocycline-aminoglycoside combination can be an alternative for infections caused by KPC-producing K. pneumoniae because this combination displays strong synergistic and bactericidal activity in susceptible isolates, and can effectively prevent the emergence of resistant mutants. Further in vitro pharmacokinetic/pharmacodynamic studies and clinical trials should be performed to fully evaluate the efficacy of this drug combination.