Potential role of moxifloxacin in methicillin-resistant Staphylococcus aureus (MRSA) infections.
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Biomedical subjects
Publications and source records attributed to T Butt.
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We evaluated FASTPlaqueTB, a recently introduced bacteriophage assay for rapid detection of Mycobacterium tuberculosis complex in sputum specimens, using 169 non-duplicate sputum specimens from patients suspected of pulmonary tuberculosis. The results of 160 specimens were analysed. FASTPlaqueTB assay detected tuberculosis in 77% (46/60) of culture-positive cases. Among the AFB smear-positive cases (n = 47) it had a sensitivity of 76% and specificity of 60% while among AFB smear-negative cases (n = 113) its sensitivity and specificity were 78% and 98%, respectively. The overall sensitivity and specificity of the technique were 77% and 96%, respectively, and the positive and negative predictive values were respectively 92% and 87%. The overall efficiency of the test was 89%. Test results were available in 48 h.
OBJECTIVE: To evaluate the performance of FASTPlaqueTB-RIF, a newly introduced bacteriophage assay for rapid detection of rifampicin susceptibility of Mycobacterium tuberculosis in sputum specimens. METHODS: A comparative study of 40 sputum specimens from patients of pulmonary tuberculosis, using FASTPlaqueTB-RIF and Bactec 460 TB system carried out at the Armed Forces Institute of Pathology, Rawalpindi between September and November 2001. RESULTS: Of the 40 clinical isolates of Mycobacterium tuberculosis tested for rifampicin (RIF) susceptibility using the Bactec 460 TB system, 28 isolates were resistant to RIF and 12 isolates were susceptible. FASTPlaqueTB-RIF identified 24 specimens as resistant to RIF. Three specimens that revealed susceptible isolates on Bactec 460, were resistant by FASTPlaqueTB-RIF while four specimens which revealed resistant isolates on Bactec 460, demonstrated susceptibility to RIF by FASTPlaqueTB-RIF. The sensitivity and specificity of FASTPlaqueTB-RIF were 86% and 73% respectively. The predictive values of positive and negative tests were 0.89 and 0.67 respectively. The overall accuracy of the technique was 82%. The phage assay took 48 hours to perform. CONCLUSION: Early detection of rifampicin resistance by the mycobacteriophage technique direct from sputum specimens is a potentially useful new test which would allow decision regarding appropriate therapy to be made early thus having a positive impact on patient care and on prevention of spread of MDR TB.
OBJECTIVE: To compare in-vitro antimicrobial susceptibility of nitrofurantoin against commonly used antimicrobials for the treatment of urinary tract infection caused by enterococci. METHODS: A total of 144 enterococci (Enterococcus faecalis, n=130, Enterococcus faecium, n=14) isolated and confirmed by biochemical tests at the department of Microbiology, Armed Forces Institute of Pathology, Rawalpindi, for a period of three years were included in the study. The antimicrobial susceptibility tests of isolated organisms were performed by standard disc diffusion method as recommended by NCCLS. In addition to nitrofurantoin (NIT), doxycycline (DOX), co-trimoxazole (COT), ampicillin (AMP), imipenem (IPM) and vancomycin (VAN) were used for antimicrobial susceptibility testing. RESULTS: One hundred and twenty seven (88%) isolates of Enterococci were susceptible to NIT while 72% (n = 103) to AMP, 13% to COT, 11% to DOX, 91% to IPM and 99% to VAN. Among the strains resistant to AMP, COT, DOX, IPM and VAN, 50-88% were susceptible to NIT. CONCLUSION: Nitrofurantoin is an effective antimicrobial in vitro and can be used for treatment of Enterococcus urinary tract infections.
OBJECTIVE: To determine the resistance pattern of Mycobacterium tuberculosis isolates in Rawalpindi-Islamabad. METHODS: The study was carried out at the Department of Microbiology, Armed Forces Institute of Pathology, Rawalpindi between September 2000 and August 2002. We examined 1359 pulmonary and extra-pulmonary specimens from suspected cases of tuberculosis. The radiometric Bactec 460 TB system was used for culture and antimicrobial susceptibility testing. RESULTS: Mycobacterium tuberculosis was isolated from 325 clinical specimens. Antimicrobial susceptibility of the isolates was tested against the four first-line anti-tuberculous drugs (rifampicin, isoniazid, streptomycin and ethambutol). Fifteen percent of the isolates were resistant to a single drug, 28% were multi-drug resistant including 7% which were resistant to all the four drugs. The overall resistance against individual drugs was rifampicin 32%, isoniazid 37%, streptomycin 19% and ethambutol 17%. CONCLUSIONS: The increasing level of drug resistance among mycobacterial isolates in our population is most alarming. Strict implementation of control measures is required to combat this unfolding crisis.
OBJECTIVE: To determine the frequency and antimicrobial susceptibility pattern of extra-pulmonary tuberculosis in Rawalpindi. SETTING: Department of Microbiology, Armed Forces Institute of Pathology, Rawalpindi. METHODS: Between September 2000 and August 2002, 899 pulmonary and 460 extra-pulmonary specimens from suspected cases of tuberculosis were examined. The radiometric BACTEC 460 TB system was used for culture and antimicrobial susceptibility testing. RESULTS: Mycobacteria were isolated from 291 pulmonary specimens and 98 extra-pulmonary specimens. The frequency of extra-pulmonary tuberculosis was 25.2%. The commonest source of isolation was pus (44.9%, frequency 11.3%), followed by lymph nodes (13.3%, frequency 3.3%) and pleural fluid (13.3%, frequency 3.3%). We tested the anti-microbial susceptibility of the isolates to the four first line anti-tuberculous drugs, rifampicin, isoniazid, streptomycin and ethambutol. Of the extra-pulmonary isolates 13.3% were resistant to a single drug, 21.4% were multi-drug resistant and 9.2% were resistant to all the four drugs. CONCLUSION: Increased awareness of the magnitude of the problem posed by extra-pulmonary tuberculosis is required so that appropriate control measures can be adopted.
OBJECTIVE: To study the bacterial pathogens causing neonatal sepsis and their sensitivity pattern so that guidelines can be prepared for empirical antibiotic therapy. SETTING: The study was conducted in the neonatal intensive care unit (NICU) at PNS Shifa (Naval Hospital), Karachi during January 1997 to June 1999. METHODS: Blood specimens for culture were drawn from 520 newborns admitted in a NICU with sepsis. The specimens were inoculated into brain heart infusion broth. Subcultures were performed on days 1, 2, 3, 5, 7 and 10. The isolates were identified by standard biochemical tests. Antibiotic resistance pattern of the isolates was studied by Modified Kirby Baur disc diffusion technique. RESULTS: A total of 212 organisms were isolated. These included Staphylococcus aureus (n = 65), Klebsiella pneumoniae (n = 73), Acinetobacter baumannii (n = 23), Escherichia coli (n = 22), Enterobacter cloacae (n = 18), Citrobacter diversus (n = 5), Pseudomonas aeruginosa (n = 4) and group B Streptococcus (n = 2). On antibiotic sensitivity testing, 61.54% of Staphylococcus aureus isolates were found to be methicillin resistant. Susceptibility to the other common drugs was also quite low while 89.23% of these were susceptible to amikacin and 100% to vancomycin. More than 90% gram negative rods were resistant to ampicillin and co-trimoxazole. Resistance to gentamicin was as high as 90.4% for Klebsiella pneumoniae; 60.87% for Acinetobacter baumannii. Resistance to the third generation cephalosporins and the quinolone tested (ciprofloxacin) varied between 25-75%. Majority of the isolates were susceptible to meropenem and amikacin. CONCLUSION: In view of the isolation of highly antibiotic resistant organisms, vancomycin in combination with amikacin or a carbapenem is the drug of choice for empirically treating neonatal sepsis.
Begomoviruses occur in many plant species in Pakistan and are associated with an epidemic of cotton leaf curl disease that has developed since 1985. PCR analysis with primer pairs specific for each of four already sequenced types of DNA-A of cotton leaf curl virus (CLCuV-PK types a, 26, 72b and 804a), or for okra yellow vein mosaic virus (OYVMV), indicated that many individual naturally infected plants of cotton and other malvaceous species contained two or three begomovirus sequences. Similarly, sequence differences among overlapping fragments of begomovirus DNA-A, amplified from individual naturally infected plants, indicated much multiple infection in malvaceous and non-malvaceous species. Some cotton plants contained DNA-A sequences typical of begomoviruses from non-malvaceous species, and some non-malvaceous plants contained sequences typical of CLCuV-PK. Some DNA-A sequences were chimaeric; they each included elements typical of different types of CLCuV-PK, or of different malvaceous and/or non-malvaceous begomoviruses. Often an apparent recombination site occurred at the origin of replication. No complete CLCuV-PK DNA-A sequence was found in malvaceous or non-malvaceous species collected in Pakistan outside the area of the cotton leaf curl epidemic but chimaeric sequences, including a part that was typical of CLCuV-PK DNA-A, did occur there. We suggest that recombination among such pre-existing sequences was crucial for the emergence of CLCuV-PK. Recombination, following multiple infection, could also explain the network of relationships among many of the begomoviruses found in the Indian subcontinent, and their evolutionary divergence, as a group, from begomoviruses causing similar diseases in other geographical regions.
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A nonhydrolyzable analogue of ubiquitin adenylate has been synthesized for use as a specific inhibitor of the ubiquitination of proteins. Ubiquitin adenylate is a tightly bound intermediate formed by the ubiquitin activating enzyme. The inhibitor adenosyl-phospho-ubiquitinol (APU) is the phosphodiester of adenosine and the C-terminal alcohol derived from ubiquitin. APU is isosteric with the normal reaction intermediate, the mixed anhydride of ubiquitin and AMP, but results from the replacement of the carbonyl oxygen of Gly76 with a methylene group. This stable analogue would be expected to bind to both ubiquitin and adenosine subsites and result in a tightly bound competitive inhibitor of ubiquitin activation. APU inhibits the ATP-PPi exchange reaction catalyzed by the purified ubiquitin activating enzyme in a manner competitive with ATP (Ki = 50 nM) and noncompetitive with ubiquitin (Ki = 35 nM). AMP has no effect on the inhibition, confirming that the inhibitor binds to the free form of the enzyme and not the thiol ester form. This inhibition constant is 10-fold lower than the dissociation constants for each substrate and 30-1000-fold lower than the respective Km values for ubiquitin and ATP. APU also effectively inhibits conjugation of ubiquitin to endogenous proteins catalyzed by reticulocyte fraction II with an apparent Ki of 0.75 microM. This weaker inhibition is consistent with the fact that activation of ubiquitin is not rate limiting in the conjugation reactions catalyzed by fraction II. APU is similarly effective as an inhibitor of the ubiquitin-dependent proteolysis of beta-lactoglobulin.(ABSTRACT TRUNCATED AT 250 WORDS)
We have constructed a convenient new vector, YEp-DE, for the construction of gene libraries and the expression of heterologous genes in Saccharomyces cerevisiae. The vector contains the yeast LEU2 gene, the 2 mu origin of replication, and a region from pUC18 that includes the ampr gene, the Escherichia coli origin of replication (ori), and the LacZ gene with multiple cloning sites. Five sites (Sac1, Sma1, BamH1, Sal1, Sph1) in this region are unique. This vector has advantages over similar yeast-E. coli shuttle vectors: small size (7291 bp, entirely sequenced), convenient cloning sites, and lacZ selection for detecting recombinant plasmids.
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We analysed the record of blood cultures carried out at the Armed Forces Institute of Pathology, Rawalpindi between 1996 and 2003. We isolated 477 Salmonella typhi and 410 S. paratyphi A from blood of patients suffering from typhoid fever. We observed a significant shift in the distribution and antimicrobial susceptibility of typhoid salmonellae. The isolation rate of S. typhi fell significantly while S. paratyphi A is emerging as a major pathogen. Resistance to conventional antityphoid drugs in S. typhi decreased dramatically from 80% to 14%, while in S. paratyphi A resistance increased from 14% to 44%. Susceptibility to the fluoroquinolones decreased in both. No resistance to third generation cephalosporins was detected.