Prevalence of methicillin-resistant staphylococci in Riyadh, Saudi Arabia and their susceptibility to antimicrobial agents.
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Biomedical subjects
Publications and source records attributed to A M Shibl.
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The incidence of beta-lactamase production by Haemophilus influenzae strains and their susceptibility to commonly used oral antimicrobial agents were evaluated. From 1990 to 1992, 600 significant isolates of H. influenzae obtained from various hospitals throughout Saudi Arabia were identified, serotyped and tested for beta-lactamase production using cefinase discs and susceptibility to various antibiotics using the agar dilution method. The study revealed that 17% of the strains produced beta-lactamase; 21% of them were type b. The overall level of resistance was 30% to erythromycin, 28% to tetracycline, 14.3% to co-trimoxazole, 6.6% to chloramphenicol, 1.8% to amoxicillin-clavulanate and 1.5% to cefaclor. About 1.3% of the strains that did not produce beta-lactamase were resistant to ampicillin. Resistance of H. influenzae to antibiotics is increasing and in several parts of the world resistance to ampicillin has reached substantial levels particularly in type b strains. Information on resistance is needed for the appropriate selection of initial empiric therapy among patients in whom H. influenzae is a suspected pathogen.
The effect of sub-MICs of azithromycin, clarithromycin and roxithromycin, as compared to erythromycin, on the production of coagulase, beta-hemolysin, lecithinase and deoxyribonuclease by Staphylococcus aureus was studied. All new macrolides completely inhibited coagulase and beta-hemolysin production and partially inhibited lecithinase and deoxyribonuclease. Such inhibition is not related either to growth inhibition or to inhibition of enzyme activity. Erythromycin, on the other hand, had no effect on coagulase or beta-hemolysin production but slightly suppressed the production of lecithinase and deoxyribonuclease. This inhibitory effect might have clinical significance if it was found to occur in vivo.
The efficacy and safety of aztreonam were evaluated in an open trial at King Khalid University Hospital, Riyadh, Saudi Arabia. A total of 45 critically-ill adult patients were enrolled in the study. All patients with documented Gram-negative infection were treated with aztreonam as monotherapy. Antibiotics active against only Gram-positive and/or anaerobic organisms were allowed. Twenty cases were clinically evaluable. Eleven had lower respiratory tract infections (pneumonia), 3 had urinary tract infections, and 6 had septicemia. Clinical signs and symptoms, cultures and other laboratory profiles were assessed prior to treatment, at 4-6 days during treatment and within 2-3 days of the end of therapy (usually 7-15 days). Nineteen out of 20 (95%) had a satisfactory clinical response. All cases with septicemia and urinary tract infections were microbiologically cured. The overall microbiological response rate was 90%. Fifty-five percent of all infections were caused by Pseudomonas aeruginosa. Two patients with Gram-negative pneumonia due to P. aeruginosa did not respond microbiologically to aztreonam therapy. No serious adverse events requiring discontinuation of aztreonam therapy were reported. No mortality occurred.
The effectiveness of six commercially available mouthwashes against common buccal organisms was studied. The minimum inhibitory concentrations (MIC) for two of the studied mouthwashes (Corsodyl and Oraldene) against buccal organisms were determined in Todd Hewitt medium with or without 5% serum. The concentration of the active substance in these two mouthwashes was in excess of the corresponding MIC. When the medium was supplemented with serum, lower MIC values were observed. Kill-time determinations, used at half the concentration of the normal preparation, revealed a rapid lethal effect for all tested mouthwashes. The slowest lethal effect was observed with Fluocaril mouthwash. When mouthwashes were tested in volunteers, an immediate significant fall in salivary bacterial counts was produced by all except Fluocaril. With the latter mouthwash the decrease was significant 2-30 minutes after rinsing. The bacterial levels returned to pre-rinse levels after 30 minutes for Listerine, after 90 minutes for both Oraldene and Mint and after 180 minutes for Corsodyl, Fluocaril and Sansilla mouthwashes. The results indicate that there is a good correlation between in vivo efficacy and in vitro determination of all mouthwash preparations.
A total of 358 recent distinct isolates of Streptococcus pneumoniae were recovered from clinical specimens of patients in various hospitals in Riyadh, Saudi Arabia. The commonest serotypes were Groups C, F, B and A. Using specific monosera for typing it was found that serotype 14 was the commonest followed by serotypes 3, 7, 1, 2, 19 and 8 respectively. The minimal inhibitory concentrations (MIC) of penicillin determined by an agar dilution method, showed that 81% were susceptible (MIC less than 0.1 mg/L), 18% were relatively resistant (MIC = 0.1-1 mg/L) and 1% showed increased resistance (MIC greater than or equal to 1.0 mg/L). The use of a 1 microgram oxacillin disc distinguished between susceptible and relatively penicillin resistant pneumococci more reliably than did the use of a penicillin disc (1 or 10 micrograms). Resistance of S. pneumoniae to tetracycline, co-trimoxazole, chloramphenicol, and erythromycin were 70%, 43%, 12% and 4% respectively. All isolates were susceptible to oral cephalosporins (cefadroxil, cephalexin, cefaclor, and cefuroxime axetil) with an MIC range of less than or equal to 0.03-2 mg/L. The selection of antimicrobial therapy and the efficiency of vaccines depend on the knowledge of the local isolates of S. pneumoniae. Clinical isolates should be routinely screened to detect susceptibility to penicillin. The relatively high incidence of resistance to multiple antibiotics indicates the need to perform antibiotic susceptibility testing in order to avoid possible therapeutic failure.
In a multicenter survey in seven Middle Eastern countries, 1,827 clinical isolates from patients with community-acquired infections (outpatients) were examined for both production of beta-lactamase and their susceptibility to commonly prescribed antibiotics. Of these isolates, 63% were gram-negative and 37% were gram-positive organisms. beta-lactamase was produced by 65% of all isolates, representing 61 and 75% of gram-negative and gram-positive organisms, respectively. Using standardized disk susceptibility testing, high rates of resistance were observed among gram-negative and gram-positive organisms, respectively, for penicillin (86 and 75%), ampicillin (67 and 66%) and amoxicillin (58 and 52%). Resistance to tetracycline and co-trimoxazole were also seen, but to a lesser degree. Susceptibility of these organisms towards the cephalosporins cepharadine, cephalexin and cefadroxil ranged from 30 to 70%, which appears to correlate fairly closely with the prevalence of beta-lactamase production. Cefuroxime inhibited about 94 and 79% of gram-positive and gram-negative organisms, respectively, regardless of the production of beta-lactamase. These data are valuable since antibiotic therapy is usually instituted on a best-guess principle against the most likely potential pathogens.
Washed intact cells of Escherichia coli and Staphylococcus aureus, grown under partial anaerobic conditions in nitrate media, reduced nitrate quantitatively when formate was used as a reducing substrate. Nitrate reductase was applied as an index for bacterial adherence to different target surfaces including uroepithelial cells, HeLa cells and fibrin clots. Nitrate reduction by adhered as well as control cells was determined by quantitative diazotization reaction for nitrite. Variations in the conditions which affect adherence gave rise to corresponding variations in the nitrate reduction index from which bacterial adherence can be conveniently determined under these conditions. This method is simple, reproducible and easy to perform in a short time.
A high-performance liquid chromatographic method (HPLC) was developed for the determination of lomefloxacin in plasma and urine and was compared to a microbiological assay. Lomefloxacin and norfloxacin (internal standard) were extracted from plasma and urine samples using chloroform. Measurements were carried out with a fluorescence detector using an excitation wavelength of 280 nm and an emission wavelength of 430 nm with a mercury lamp. Quantification was achieved by the measurement of the peak-height ratio and the analytical recovery of the drug from plasma and urine was found to be (mean +/- SD) 99.3 +/- 3.74% and 95.7% +/- 3.82%, respectively. In the microbiological assay, E. coli ATCC 1346 was the test organism using an agar diffusion technique. The coefficients of variation for within-day analysis for both the HPLC method and microbiological assay from plasma samples were less than 7%. The minimum detectable concentration for both the HPLC and the microbiological method was 50 ng/ml and 100 ng/ml, respectively. Both methods were used to determine the lomefloxacin level in plasma following intravenous administration to mice. Excellent agreement was obtained between the results of the two methods. The HPLC method offers significant advantages in accuracy, precision, speed of analysis and turnover-time.
The in vitro activity of cefroxadine was studied and found to be at least comparable to that previously reported for cefalexin and cefradine. The activity of cefroxadine was superior to that of amoxicillin against tested isolates. Time-killing studies showed that the addition of 4 X minimum inhibitory concentration (MIC) of cefroxadine to growing cultures reduced viable counts by 4 log units within a 3 h incubation. A diffusion test with a 30 microgram cefroxadine disk produced acceptable interpretive results with tentative zone size breakpoints of less than or equal to 14 mm for resistance and greater than or equal to 17 mm for susceptibility.
There has been considerable recent interest in the nature and importance of interactions which occur between antibiotics, microorganisms and the various cellular and humoral components of the host. The influence of antibiotics on host defense mechanisms is important because of the increasing number of compromised hosts in whom even a marginal influence on the host response may have a significant effect of the outcome. The influence of antibiotics on host/bacterial interaction reveals subtle effects on the ultrastructure of the bacterial cell, the biosynthesis of various virulence factors, the ability of microorganisms to adhere to epithelial cells and the function of polymorphonuclear leukocytes and the immune-specific response of mononuclear cells. These effects permit the proposal that at least some of the subtle effects of antibiotics on microbial pathogenicity might take place in vivo. If antibiotics can be shown definitely to enhance host-defense mechanisms, especially in compromised hosts, then more effective antibiotic therapy can be provided for these indications. Finally if antibiotics can modify the outcome of host-parasite interactions then perhaps we need to consider testing antibiotics against these parameters.
Ciprofloxacin, pefloxacin, norfloxacin, and ofloxacin were investigated for immunomodulatory activity on humoral and cell-mediated immune responses. Ciprofloxacin and pefloxacin altered the humoral immune responses of mice to sheep red blood cells. This effect was not exhibited by norfloxacin or ofloxacin. All four quinolones did not alter cell-mediated responses. When these antimicrobial agents were tested for their interaction with human polymorphonuclear phagocytic activity, all agents suppressed this activity. In addition, all except norfloxacin showed anti-inflammatory activity.
Artemisinin and nine of its semisynthetic derivatives were tested for antibacterial activity against anaerobic, facultative anaerobic, microaerophilic and aerobic bacteria. Only anaerobic bacteria and gonococci showed sensitivity to artemisinin derivatives. Artemisinin and its deoxy derivatives had no activity at 100 micrograms/ml concentration. The newly synthesized methyl diperoxy derivative had the highest activity against all tested anaerobes with a MIC of 9.4 micrograms/ml.
The in vitro antibacterial activity of aztreonam was compared with that of cefoperazone, cefotaxime, ceftazidime, gentamicin, latamoxef, and ticarcillin against 140 clinical isolates of gram-negative bacteria. The activity of aztreonam against Enterobacteriaceae is similar to that of cefotaxime and ceftazidime but greater than that of gentamicin, latamoxef, and ticarcillin. The 90% minimum inhibitory concentration (MIC90) of most of these isolates ranges between 0.8 and 1.6 micrograms/ml. The activity of aztreonam against Pseudomonas aeruginosa is similar to that of cefotaxime and cefoperazone, more active than that of latamoxef, and less active than that of ceftazidime. The minimum bactericidal concentration of aztreonam is equal to or twice the MIC for most strains tested. Time-kill studies of selected strains demonstrated rapid killing when they were exposed to 2-4 times the MIC of aztreonam. The selective spectrum of action of aztreonam makes this drug a useful agent in the therapy of a variety of gram-negative infections.
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Streptococcus pneumoniae is the most common cause of bacterial pneumonia, otitis media, bacteremia, and meningitis in infants, children, and immunocompromised and splenectomized patients. After the introduction of penicillin in 1940, pneumococci were regarded as uniformly sensitive to minimal inhibitory concentrations (less than or equal to 0.05 microgram/mL). This idea persisted until 1967, when the first strain showing increased resistance to penicillin was isolated. Pneumococci with intermediate penicillin resistance recovered from different geographic areas have minimum inhibitory concentrations of 0.1 to 1.0 microgram/mL. In 1977, however, resistant strains were isolated with minimum inhibitory concentrations of 2 to 10 micrograms/mL; subsequently, strains resistant to other antibiotics including tetracycline, sulfonamides, erythromycin, lincomycin, chloramphenicol, clindamycin, streptomycin, and rifampin have also been reported. The authors emphasize the need for continued surveillance of pneumococcal isolates and recommend sensitivity testing of all isolates to penicillin.
The antistaphylococcal activity of teicoplanin, a new glycopeptide antibiotic, has been evaluated in vitro and compared with that of vancomycin, fucidin, rifampicin and gentamicin. Teicoplanin was found to be as active as vancomycin against clinical isolates of Staphylococcus aureus (both methicillin-resistant and methicillin-sensitive strains). Teicoplanin was found to be more active than vancomycin against Staphylococcus epidermidis. The minimum inhibitory concentration (MIC) of teicoplanin was 2- to 4-fold lower than that of other drugs tested. The minimum bactericidal concentration (MBC) of both teicoplanin and vancomycin either equalled or exceeded by 2-fold the respective MIC's. The rate at which staphylococci were killed showed that teicoplanin at 4 X MIC produced rapid killing in 10 h and no growth was detected after 24 h.