Diagnostic microbiology and therapeutic drug monitoring in pediatric infectious diseases.
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Adolescent↗
Biomedical subjects
M R Jacobs
Publications and source records attributed to M R Jacobs.
Once-daily vs. continuous aminoglycoside dosing: efficacy and toxicity in animal and clinical studies of gentamicin, netilmicin, and tobramycin.
The dosing frequency of aminoglycoside antibiotics may alter efficacy and toxicity independent of total daily dose. Once-daily tobramycin dosing was compared with continuous infusion in three models of efficacy. Acute pneumonia due to Pseudomonas aeruginosa in guinea pigs responded better to once-daily dosing, and chronic pneumonia in rats and endocarditis in rabbits responded equally to both regimens. Dogs given gentamicin, tobramycin, or netilmicin once daily, with maximum serum concentrations of greater than 100 mg/liter, had less nephrotoxicity than dogs given continuous infusions. Tobramycin was given once daily or continuously to 52 patients with cystic fibrosis who in 10 days had no change in creatinine clearance or hearing despite maximum serum tobramycin concentrations of 40 mg/liter. Intermittent dosing of aminoglycosides, causing infrequent large maximum serum concentrations, may be less toxic and equally efficacious as frequent dosing.
Adult↗
Susceptibility of penicillin-resistant pneumococci to eighteen antimicrobials: implications for treatment of meningitis.
The minimal inhibitory concentrations (MICs) of 18 antibiotics including 16 beta-lactam antibiotics were determined by agar dilution on 70 strains of pneumococci (25 penicillin sensitive, 18 intermediate resistant and 27 resistant). The antimicrobials tested were penicillin G, ampicillin, carbenicillin, ticarcillin, piperacillin, mezlocillin, cephalothin, cefoxitin, cefamandole, latamoxef (moxalactam), cefotaxime, cefoperazone, ceftazidime, ceftriaxone, N-formimidoyl thienamycin, SCH 29482, chloramphenicol and vancomycin. Of these agents, only cefotaxime demonstrated greater activity than penicillin against intermediate penicillin-resistant strains while cefoperazone, ceftriaxone, N-formimidoyl thienamycin and vancomycin as well as cefotaxime demonstrated activity superior to penicillin against penicillin-resistant strains. Comparison of the MIC90s of these agents with the achievable cerebrospinal fluid levels suggests that meningitis caused by penicillin-resistant pneumococci should respond to treatment with cefotaxime, cefoperazone, ceftriaxone and vancomycin.
Anti-Bacterial Agents↗
Penicillin-resistant pneumococcus and meningitis.
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Aged↗
Comparative efficacies of ceftriaxone, moxalactam, and ampicillin in experimental Salmonella typhimurium infection.
The activities of ceftriaxone, moxalactam, and ampicillin against Salmonella typhimurium LT-2 were compared in culture media at pH 5, 6, 7 and 8 and in mice inoculated intraperitoneally. The minimal inhibitory concentrations for strain LT-2 in Mueller-Hinton broth were 0.03 microgram of ceftriaxone per ml, 0.08 microgram of moxalactam per ml, and 0.4 microgram of ampicillin per ml. A comparison of minimal inhibitory concentrations in buffered broth at pH 5 with those in media at higher pH values showed that ceftriaxone was more acid stable than the other antibiotics. Groups of CF-1 female mice inoculated intraperitoneally with 3 X 10(4) colony-forming units received saline or each drug in fourfold decremental doses by the subcutaneous route every 8 h for 3 days, beginning at 24 h after challenge. The mean log 10 colony-forming units of S. typhimurium per spleen at the end of treatment and the mortality rates at 21 days after inoculation were measured for each treatment group. The mean log 10 colony-forming units per spleen was significantly reduced from that of the saline control by dosages of greater than or equal to 0.06 mg of ceftriaxone per kg, 64 mg of moxalactam per kg, or greater than or equal to 16 mg of ampicillin per kg (P less than 0.05). Mortality rates of infected mice were significantly reduced by dosages of greater than or equal to 1 mg of ceftriaxone per kg or greater than or equal to 64 mg of ampicillin per kg (P less than 0.05), whereas moxalactam in dosages as high as 16 mg/kg did not significantly reduce mortality rate. These results demonstrate the superiority of ceftriaxone to the other tested antibiotics on a weight basis in this model of experimental Salmonella infection.
Ampicillin↗
Susceptibility of group B streptococci to 16 beta-lactam antibiotics, including new penicillin and cephalosporin derivatives.
The susceptibility of 100 group B streptococci to 16 beta-lactam antibiotics was tested by agar dilution. Penicillin G and N-formimidoyl thienamycin were the most active agents tested, both having a 90% minimal inhibitory concentration (MIC90) of 0.06 microgram/ml. Ceftriaxone, cefotaxime, cefamandole, and SCH 29482 were almost as active, all having an MIC90 of 0.12 microgram/ml, and ampicillin, cephalothin, and mezlocillin all had an MIC90 of 0.25 microgram/ml. The MIC90 for piperacillin, cefoperazone, and ceftazidime was 0.5 microgram/ml. Least active were carbenicillin, ticarcillin, cefoxitin, and moxalactam, with MIC90s of 1, 2, 4, and 8 micrograms/ml, respectively. No penicillin-tolerant strains were detected.
Anti-Bacterial Agents↗
Penicillin susceptibility testing of gonococci by disc diffusion.
This study investigated the use of various beta-lactam discs in the detection of penicillin sensitive, intermediate resistant and resistant strains (minimal inhibitory concentrations of penicillin G of less than 0.06, 0.06 to 0.25, and greater than 0.25 mg/l respectively). Discs containing 0.15 and 0.6 microgram of penicillin G, and 5 microgram of methicillin were the most useful in separating the three groups. Cut-off zones between sensitive, intermediate resistant and resistant strains are 12 and 24 mm for 0.15 microgram penicillin discs; 24 and 32 mm for 0.6 microgram penicillin discs; and 20 and 30 mm for 5 microgram methicillin discs. Oxacillin discs (1 microgram) were useful in separating resistant from both sensitive and intermediate resistant strains at a cut-off zone of 8 mm. Use of a combination of discs provides the best index of susceptibility group, and at least two should be used
Dose-Response Relationship, Drug↗
Botulism: a case report.
The 4th case of botulism in South Africa is reported. Unusual features are the detection of toxin in the patient's serum 7 weeks after the onset of the illness and the need for 14 weeks' intermittent positive pressure ventilation. Symptomatic treatment and meticulous nursing resulted in complete recovery. The microbiology, pathophysiology, clinical features, diagnosis and management of botulism are briefly reviewed.
Adult↗
Antimicrobial susceptibility testing of pneumococci. 2. Determination of optimal disc diffusion test for detection of penicillin G resistance.
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Diffusion↗
Yersinia enterocolitica biotype 1 in South Africa.
Two clinical isolates of Yersinia enterocolitica biotype 1, positive for indole and lecithinase production, xylose and salicin fermentation, and aesculin hydrolysis, are reported. One strain, serotype 0 6, was recovered from a healthy food handler, while the other, serotype 0 5, was associated with a diarrhoeal illness in a 1-year-old child. This is the first report of either of these serotypes from human material in South Africa.
Adult↗
Resistance mechanisms of multiply resistant pneumococci: antibiotic degradation studies.
Strains of Streptococcus pneumoniae resistant to penicillin have been reported from several countries around the world. Many South African isolates, in addition, exhibit resistance to tetracycline, chloramphenicol, erythromycin, clindamycin, and cotrimoxazole in varying patterns. A qualitative test of the ability of antibiotic-resistant pneumococci to inactivate penicillin, oxacillin, cephalothin, cefoxitin, chloramphenicol, tetracycline, minocycline, erythromycin, clindamycin, streptomycin, gentamicin, and cotrimoxazole revealed that only chloramphenicol was degraded. This finding was confirmed in a quantitative test in which the residual antimicrobial activity of broth containing chloramphenicol in subinhibitory concentrations was determined after incubation with antibiotic-resistant bacteria. Chloramphenicol resistance was shown to be associated with the production of inducible chloramphenicol acetyltransferase. No beta-lactamase activity was demonstrated. Plasmid deoxyribonucleic acid was not demonstrable in partially purified lysates of antibiotic-resistant strains of S. pneumoniae.
Acetyltransferases↗
Antimicrobial susceptibility testing of pneumococci: determination of Kirby-Bauer breakpoints for penicillin G, erythromycin, clindamycin, tetracycline, chloramphenicol, and rifampin.
Antimicrobial susceptibility testing of pneumococci is now essential to monitor for the presence of resistance to agents such as the penicillins, macrolides, lincomycins, chloramphenicol, and tetracycline. In this study, clinical isolates of a selection of resistant South African strains were tested for antimicrobial susceptibility by minimal inhibitory concentration (MIC) determination and by a modified Kirby-Bauer disk diffusion technique, using Mueller-Hinton medium supplemented with 5% horse blood. Disk diffusion breakpoints were determined for penicillin G, erythromycin, clindamycin, tetracycline, chloramphenicol, and rifampin. Reliable results were obtained on disk diffusion for all these agents except for penicillin G. With 6-mug penicillin G disks, zones of strains with intermediate penicillin susceptibility overlapped those of sensitive and resistant strains. With 5-mug methicillin disks, clearer separation of strains based on susceptibility to penicillin G occurred. Strains with zones of <35 mm around penicillin G disks and <25 mm around methicillin disks should have penicillin G MICs determined to confirm their resistance to penicillin G. In view of the potential for pneumococci to be resistant to the agents used in this study, antimicrobial susceptibility of all clinically significant isolates should be determined.
Chloramphenicol↗
Resistant pneumococcal infections.
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Adolescent↗
Antibacterial activity of nitroxoline and sulphamethizole alone and in combination in urinary tract infections.
In vitro studies on the antibacterial activity of nitroxoline and sulphamethizole, alone and in combination, were undertaken and minimal inhibitory concentrations (MICs) determined on a range of urinary pathogens. Eighty per cent of the strains tested were sensitive to less than or equal to 16 mg/l of nitroxoline, and all strains, including Pseudomonas aeruginosa and Streptococcus faecalis, were sensitive to less than or equal to 64 mg/l of nitroxoline. No synergism could be demonstrated with sulphamethizole, but the combination was antagonistic when tested against strains of Ps. aeruginosa and Strep. faecalis. An in vivo study on 10 volunteers showed excellent urinary levels of nitroxoline and sulphamethizole after an oral dose of 160 mg of each agent, and 6-hour urinary nitroxoline levels were greater than or equal to 64 mg/l in 9 of the 10 subjects, and sulphamethizole levels were greater than or equal to 64 mg/l in all 10 subjects. Laboratory findings suggest that nitroxoline and sulphamethizole are both suitable agents for use in urinary tract infections caused by organisms sensitive to these agents, but there appears to be litte advantage in using them in combination.
Drug Combinations↗
Emergence of multiply resistant pneumococci.
Multiple antimicrobial resistance in pneumococci was detected in Johannesburg in July, 1977, and prompted an investigation of the prevalence of resistant strains in two hospitals. Carriers of Types 6A and 19A penicillin-resistant pneumococci, resistant to antibiotic concentrations ranging between 0.12 and 4 microgram per milliliter were found in 29 per cent of 543 pediatric patients and 2 per cent of 434 hospital staff members. Multiply resistant Type 19A strains, resistant to beta-lactam antibiotics, erythromycin, clindamycin, tetracycline and chloramphenicol, were isolated from 128 carriers, and were responsible for bacteremia in four patients. Isolates from 40 other carriers were resistant to penicillin alone or to penicillin and chloramphenicol or to penicillin, chloramphenicol and tetracycline. Pneumococci can be screened for penicillin resistance with a modified Kirby--Bauer technic; the strains with zones of less than 35 mm around 6-microgram penicillin disks or less than 25 mm around 5-microgram methicillin disks should be tested for sensitivity to penicillin by measurements of minimum inhibitory concentration.
Adult↗
Enteric fever caused by Salmonella paratyphi C in South and South West Africa.
This article documents 53 cases of Salmonella paratyphi C infections in humans in the Eastern Transvaal (47 cases) and South West Africa (6 cases). Ninety-two percent of patients (49 cases) had enteric fever, 1 patient was asymptomatic, and 3 had localized urinary infections or were carriers. Most patients were successfully treated with chloramphenicol and only 1 relapsed. The South West African strains were identified as S. paratyphi C var. east africa. The organism is probably spread by water, and 70% of patients who had enteric fever were under the age of 20 years.
Adolescent↗
Epidemic listeriosis. Report of 14 cases detected in 9 months.
During the period August 1977 to April 1978, 14 Black patients in Johannesburg area had systemic infections caused by Listeria monocytogenes. Nine of these patients were neonates who presented with septicaemia (5 cases) or septicaemia and meningitis (4 cases) and 5 were adults, all of whom had meningitis. The mortality rate was 43% (6/14), with 4 neonatal and 2 adult deaths. All isolates of L. monocytogenes were type 4b. Only sporadic cases of human listeriosis have previously been reported in South Africa, and the cases reported here constitute the first epidemic in this country.
Adult↗
Group B streptococcal infections in neonates and infants. Report of 16 cases, with referrence to the fatal outcome in late-onset leucopenic cases.
Sixteen cases of group B streptococcal (GBS) infections in neonates and infants aged up to 3 months were detected from November 1973 to January 1977. Three patients presented with pneumonia, 10 with meningitis and 3 with both pneumonia and meningitis. All diagnoses were confirmed by positive blood and/or cerebrospinal fluid cultures. The serotypes involved were type Ia (2 cases), type II (4 cases) and type III (10 cases). Ten patients died (62.5%). Early antibiotic treatment did not appear to affect the outcome, but low peripheral leucocyte count indicated a uniformly fatal outcome in 6 cases where leucopenia was documented, and this appeared to be associated with late-onset disease. The current status of GBS disease is presented, with particular reference to the control measures at present available and the possibility of immunotherapy and vaccination.
Diagnosis, Differential↗