- Antibacterial Activity of Human Simulated Epithelial Lining Fluid Concentrations of Ceftazidime-Avibactam Alone or in Combination with Amikacin Inhale (BAY41-6551) against Carbapenem Resistant Pseudomonas aeruginosa and Klebsiella pneumoniae. [Journal Article]
- AAAntimicrob Agents Chemother 2018 Jun 18
- The role of inhalational combination therapy when treating carbapenem resistant Pseudomonas aeruginosa and Klebsiella pneumoniae with newer beta-lactam/beta-lactamase inhibitors has not been establis...
The role of inhalational combination therapy when treating carbapenem resistant Pseudomonas aeruginosa and Klebsiella pneumoniae with newer beta-lactam/beta-lactamase inhibitors has not been established. Using a 72 hour in vitro pharmacodynamic chemostat model, we simulated the human exposures achieved in epithelial lining fluid (ELF) following intravenous ceftazidime-avibactam (CZA) 2.5g q8h alone and in combination with inhaled amikacin (AMK) 400mg q12h, a reformulated aminoglycoside designed for inhalational administration, against 3 P. aeruginosa (CZA MICs: 4/4-8/4 μg/ml; AMK-I MICs: 8-64 μg/ml) and 3 K. pneumoniae (CZA: 1/4-8/4 μg/ml; AMK-I: 32-64 μg/ml). Combination therapy resulted in a significant reduction in 72 hour colony forming units (CFU) compared with CZA monotherapy against 2 of 3 P. aeruginosa (-4.14 log10CFU/ml, P= 0.027; -1.42 log10CFU/ml, P=0.020; and -0.4 log10CFU/ml, P= 0.298) and 2 of 3 K. pneumoniae (0.04 log10CFU/ml, P=0.963; -4.34 log10CFU/ml, P < 0.001; and -2.34 log10 CFU/ml, P=0.021). When measured by the area under the bacterial growth curve (AUBC) over 72 hours, significant reductions were observed in favor of the combination regimen against all 6 isolates tested. AMK-I combination therapy successfully suppressed CZA resistance development in one K. pneumoniae harboring blakpc3 that was observed during CZA monotherapy. These studies suggest a beneficial role for combination therapy with intravenous CZA and inhaled AMK when treating pneumonia caused by carbapenem resistant Gram-negative bacteria.
- Seasonal Variations in Water-Quality, Antibiotic Residues, Resistant Bacteria and Antibiotic Resistance Genes of Escherichia coli Isolates from Water and Sediments of the Kshipra River in Central India. [Journal Article]
- IJInt J Environ Res Public Health 2018 Jun 17; 15(6)
- CONCLUSIONS: Antibiotic pollution, resistance and resistance genes in the Kshipra River showed significant seasonal variation. Guidelines and regulatory standards are needed to control environmental dissemination of these “pollutants” in this holy river.
- TB-EFI, a novel 18-Plex microbead-based method for prediction of second-line drugs and ethambutol resistance in Mycobacterium tuberculosis complex. [Journal Article]
- JMJ Microbiol Methods 2018 Jun 15
- Several diagnostic tests are being developed to detect drug resistance in tuberculosis. In line with previous developments detecting rifampicin and isoniazid resistance using microbead-based systems ...
Several diagnostic tests are being developed to detect drug resistance in tuberculosis. In line with previous developments detecting rifampicin and isoniazid resistance using microbead-based systems (spoligoriftyping and TB-SPRINT), we present here an assay called TB-EFI detecting mutations involved in resistance to ethambutol, fluoroquinolones and the three classical injectable drugs (kanamycin, amikacin and capreomycin) in Mycobacterium tuberculosis. The proposed test includes both wild-type and mutant probes for each targeted locus. Basic analysis can be performed manually. An upgraded interpretation is made available in Excel 2016®. Using a reference set of 61 DNA extracts, we show that TB-EFI provides perfect concordance with pyrosequencing. Concordance between genotypic resistance and phenotypic DST was relatively good (72 to 98% concordance), with lower efficiency for fluoroquinolones and ethambutol due to some untargeted mutations. When compared to phenotypical resistance, performances were similar to those obtained with Hain MTBDRsl assay, possibly thanks to the use of automatized processing of data although some mutations involved in fluoroquinolone resistance could not be included. When applied on three uncharacterized sets, phenotype could be predicted for 51% to 98% depending on the setting and the drug investigated, detecting one extensively drug-resistant isolate in each of a Pakistan and a Brazilian set of 91 samples, and 9 XDR among 43 multi-resistant Kazakhstan samples. By allowing high-throughput detection of second-line drugs resistance and of resistance to ethambutol that is often combined to second-line treatments, TB-EFI is a cost-effective assay for large-scale worldwide surveillance of resistant tuberculosis and XDR-TB control.
- A retrospective study on mcr-1 in clinical Escherichia coli and Klebsiella pneumoniae isolates in China from 2007 to 2016. [Journal Article]
- JAJ Antimicrob Chemother 2018 Apr 17
- CONCLUSIONS: mcr-1-carrying E. coli and K. pneumoniae displayed a lower prevalence and abundant phylogenetic diversity in mainland China. mcr-1-positive E. coli showed significant differences in antimicrobial resistance profiles compared with mcr-1-negative E. coli strains, suggesting physicians may consider prescribing different antibiotics when faced with infections caused by mcr-1-positive pathogens.
- [Prevalence and susceptibility pattern of bacteria isolated from infected chronic wounds in adult patients]. [Journal Article]
- RCRev Chilena Infectol 2018; 35(2):155-162
- CONCLUSIONS: These data provide epidemiological information on chronic wound infections, representing support for diagnosis, treatment and management of this pathology.
- [Microorganisms isolated from blood cultures in children with cancer and high-risk febrile neutropenia from five hospitals in Santiago, Chile, 2012-2015]. [Journal Article]
- RCRev Chilena Infectol 2018; 35(2):140-146
- CONCLUSIONS: This study updates the etiology and resistance profile of microorganisms isolated in BC from children with cancer and high risk FN, an essential tool for the adequate management of these patients.
- Nebulized Versus IV Amikacin: Systemic Antibiotics Treatment Modalities May Hamper Results. [Journal Article]
- CCCrit Care Med 2018; 46(7):e732
- Differential drug susceptibility patterns of Mycobacterium chimaera and other members of the Mycobacterium avium-intracellulare complex. [Journal Article]
- CMClin Microbiol Infect 2018 Jun 12
- CONCLUSIONS: Drug susceptibility patterns of M. chimaera are comparable to those of closely related species. Except for clarithromycin, breakpoints for MAIC should be reevaluated. Statistical determination of the 99.0 % ECOFF may be superior to visual approximation.
- Ceftazidime/Avibactam for Refractory Bacteremia, Vertebral Diskitis/Osteomyelitis with Pre-Vertebral Abscess and Bilateral Psoas Pyomyositis Secondary to Klebsiella Pneumoniae Carbapenemase-Producing Bacteria (KPC). [Journal Article]
- PRP R Health Sci J 2018; 37(2):128-131
- A 36-year-old man was admitted to the intensive care unit due to diabetic ketoacidosis and pneumonia requiring mechanical ventilation. Three weeks after admission, he developed a refractory bacteremi...
A 36-year-old man was admitted to the intensive care unit due to diabetic ketoacidosis and pneumonia requiring mechanical ventilation. Three weeks after admission, he developed a refractory bacteremia with Klebsiella pneumoniae carbapenemase-producing bacteria (KPC). He remained febrile and with bacteremia for six weeks despite therapy with polymyxin B, carbapenems, and amikacin. Imaging studies looking for deep-seated infection revealed vertebral L1-L2 diskitis and osteomyelitis with pre-vertebral abscess and bilateral psoas pyomyositis that were not amenable for drainage. In view of the refractory infection and the activity against KPC described in the literature, we decided to switch the patient to ceftazidime/avibactam. After six weeks of therapy, there was complete resolution of the infectious processes. We present an instance of clinical success with ceftazidime/avibactam for the treatment of refractory KPC bacteremia, vertebral diskitis and osteomyelitis with pre-vertebral abscess and bilateral psoas pyomyositis. This experience serves as reference to support treatment with ceftazidime/avibactam in similar complicated cases.
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- GeneReviews® [BOOK]
- BOOKUniversity of Washington, Seattle: Seattle (WA)
- Mitochondrial nonsyndromic hearing loss and deafness is characterized by sensorineural hearing loss (SNHL) of variable onset and severity. Pathogenic variants in MT-RNR1 can be associated with predis...
Mitochondrial nonsyndromic hearing loss and deafness is characterized by sensorineural hearing loss (SNHL) of variable onset and severity. Pathogenic variants in MT-RNR1 can be associated with predisposition to aminoglycoside ototoxicity and/or late-onset SNHL. Hearing loss associated with aminoglycoside ototoxicity is bilateral and severe to profound, occurring within a few days to weeks after administration of any amount (even a single dose) of an aminoglycoside antibiotic such as gentamycin, tobramycin, amikacin, kanamycin, or streptomycin. Pathogenic variants in MT-TS1 are usually associated with childhood onset of SNHL that is generally nonsyndromic – although the MT-TS1 substitution m.7445A>G has been found in some families who also have palmoplantar keratoderma (scaling, hyperkeratosis, and honeycomb appearance of the skin of the palms, soles, and heels).