Efficacy and safety of miglustat in the treatment of GM2 gangliosidosis: A systematic review.

BACKGROUND: Since the results of previous studies regarding the safety and efficacy of miglustat in GM2 gangliosidosis (GM2g) were inconsistent, we aimed to assess miglustat therapy in GM2g patients. METHODS: This study followed the latest version of PRISMA. We included the observational or interventional studies reporting GM2g patients under miglustat therapy by searching PubMed, Web of Science, and Scopus. Data extracted included the natural history of individual patient data, as well as the safety and efficacy of miglustat in GM2g patients. The quality assessment was performed using the Joanna Briggs Institute Critical Appraisal checklist. RESULTS: A total of 1023 records were identified and reduced to 621 after removing duplicates. After screening and applying the eligibility criteria, 10 articles and 2 abstracts met the inclusion criteria. Overall, the studies represented 54 patients with GM2g under treatment with miglustat and 22 patients with GM2g in the control group. Among patients with available data, 14 and 54 have been diagnosed with Sandhoff disease and Tay-Sachs disease, respectively. Patients included in this review consisted of 23 infantile, 4 late-infantile, 18 juvenile, and 31 adult-onset GM2g. CONCLUSIONS: Although miglustat should not be considered a definite treatment for GM2g, it appears that patients, particularly those with infantile or late-infantile GM2g, could benefit from miglustat therapy to some extent. We also make some suggestions regarding future studies presenting their findings in a standard format to facilitate pooling the available data in such rare diseases for a more comprehensive conclusion.

Molecular evaluation of aminoglycosides resistance and biofilm formation in Klebsiella pneumoniae clinical isolates: A cross-sectional study.

Background and Aims: Resistance to antibiotics and the capability to develop biofilm as two main virulent determinants of Klebsiella pneumoniae have important role in infection persistence. The aim of the study was to evaluate the association between the prevalence of aminoglycoside resistance and virulence genes and biofilm formation capacity in K. pneumoniae strains isolated from hospitalized patients in South-West of Iran. Methods: A total of 114 non-duplicate clinical isolates of K. pneumoniae collected from Ahvaz teaching hospitals. Identification of species was performed by biochemical tests and then confirmed by polymerase chain reaction (PCR) of rpoB gene. The susceptibility to antibiotics was determined by Kirby-Bauer disk diffusion method. Biofilm formation was assessed by microtiter plate method. Finally, PCR was conducted to detect virulence gene determinants including fimbrial genes, aminoglycoside modifying enzymes- and 16S rRNA methylase (RMTase) genes. Results: Totally, all collected strains were carbapenem resistant and showed multidrug- and extensively drug-resistance phenotype (75% and 25%, respectively). Seventy-one percent (n = 81) of isolates were non-susceptible to aminoglycosides. Among aminoglycoside antibiotics, K. pneumoniae isolates showed the highest and lowest resistance rates to tobramycin (71%) and the amikacin (25%), respectively. All biofilm producer strains were positive for the presence virulence determinants including ecpA, fimA, mrkD, and mrkA. Of 81 aminoglycosides non-susceptible isolates 33% were positive for the presence ant (2″)-Ia as the most prevalent gene followed by aac (3')-IIa and armA (27%), aac (6')-Ib (18%), and aph (3')-Ia (15%). Conclusion: K. pneumoniae isolates showed the highest and the lowest aminoglycoside resistance rates to tobramycin and amikacin, respectively. Majority of isolates were biofilm producers and there was significant association between antibiotic resistance pattern and the strength of biofilm production. The ant(2″)-Ia, aac (3')-IIa, and armA genes in aminoglycoside-resistant isolates.

Drug susceptibility profiling and genetic determinants of drug resistance in Mycobacterium simiae isolates obtained from regional tuberculosis reference laboratories of Iran.

BACKGROUND: Among Non-tuberculous mycobacteria (NTM) which generally cause opportunistic infections, especially in immunocompromised hosts, Mycobacterium simiae (M. simiae) is one of the most important NTM, associated with pulmonary disease. The main concern about M. simiae infections is the extreme resistance of this NTM to antibiotics. There are limited studies about drug susceptibility testing (DST) and the causes of drug resistance in M. simiae. Hence, the current study aimed to identify the M. simiae isolates and to assess the drug resistance of the isolates using phenotypic and molecular methods. MATERIALS AND METHODS: In this study, 50 clinical pulmonary isolates suspected of NTM were collected from regional tuberculosis reference laboratories in Iran. The isolates were identified as M. simiae by using standard biochemical tests and molecular methods. DST was performed for identified M. simiae isolates and additional 35 M. simiae isolates from the department archive, against eight drugs. The mutations in gyrA, gyrB, and rrl genes in clarithromycin and moxifloxacin resistant isolates were investigated by polymerase chain reaction (PCR) followed by sequencing. RESULTS: Out of 50 suspected NTM isolates, 25 isolates were detected as M. simiae species based on the biochemical tests, and 18 isolates were verified based on the rpoB gene sequence analysis to achieve a total of 53 isolates when the archive isolates were included. DST results showed that all 53 isolates were resistant to isoniazid, rifampin, and clofazimine. The rate of resistance to ethambutol and linezolid were 34 (64%), and 40 (76%) respectively. The highest susceptibility rate was demonstrated for amikacin 53 (100%) and clarithromycin 45(85%), followed by moxifloxacin 35(66%). Sequence analysis showed mutations in positions 2058 and 2059 of the rrl gene, as well non-synonymous mutation at codons 389, 444, and 571 of the gyrB gene. Sequence analysis showed no mutation in the gyrA gene. drug-resistant isolates with mutations showed higher MICs compared to non-mutant resistant isolates. CONCLUSIONS: This study revealed amikacin, clarithromycin, and moxifloxacin as the most effective antibiotics. However, since M. simiae exhibited a high level of antibiotic resistance in vitro, therefore, species identification and determining the antibiotic susceptibility pattern of the isolates are essential before treatment.