Guide to HIV care defended.
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Biomedical subjects
Publications and source records attributed to R L Perkins.
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Patients undergoing elective intraabdominal operations received a three-dose prophylactic regimen of either moxalactam (83 patients) or cefazolin (98 patients) in a blinded, randomized fashion. There was a 9% overall infection rate with 6% for those in the cefazolin group (6/98), and 12% for those treated with moxalactam (10/83) (p = 0.26). Infection rates stratified by types of surgery were similar for both regimens. The drugs were well tolerated, with minimal side effects. Patients at highest risk of infection were those with obstruction of upper gastrointestinal tract and those with pancreatitis. We concluded that moxalactam was no more effective than cefazolin in preventing postoperative infections in this study population.
Cefmenoxime was evaluated in an open trial consisting of 41 patients. Forty infections in 36 patients could be evaluated. Thirteen patients had pyelonephritis due to Escherichia coli (two bacteremic), Pseudomonas aeruginosa, Klebsiella pneumoniae, or Streptococcus faecalis; all improved and 12 of 13 were clinically cured, but one relapse (S. faecalis) occurred at two weeks. Six patients with cystitis due to E. coli, Citrobacter freundii, Serratia marcescens, P. aeruginosa, or S. faecalis all improved, but relapse or reinfection, or both, occurred in five due to P. aeruginosa, S. faecalis, C. fruendii, or E. coli. Neurogenic bladder or other complications were present in five of 13 patients with pyelonephritis and five of six with cystitis. Ten patients with pneumonia and one with tracheobronchitis due to Hemophilus influenzae, S. pneumoniae, S. agalactiae, or Neisseria meningitidis all improved and seven had resolution without relapse, but P. aeruginosa emerged in two patients, one of whom died. Eight soft tissue infections due to Staphylococcus aureus, Peptococcus prevotti, Streptococcus species, or infections of mixed origin resolved in six. Sterility of blood cultures was obtained in one patient with endocarditis due to S. anginosus, but other therapy was substituted. Clinical resolution of the toxic shock syndrome and subsequent negative endocervical cultures for S. aureus occurred in one. Granulocytopenia of unverified cause in four (with less than 1,500 mm3) and two (with less than 2,000 mm3) was reversible. Headache during treatment occurred in six patients and a possible disulfiram-like effect in three. Elevations of serum glutamic oxalacetic transaminase and alkaline phosphatase occurred in five, Coombs' positivity in two, and diarrhea in three. Clinical efficacy of cefmenoxime was significant. Possible side effects require further study.
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The pharmacokinetic and antibacterial properties of cefotaxime were determined in normal adult volunteers. Single doses of 250, 500, 1,000 and 2,000 mg were evaluated following 5- and 20-min intravenous (i.v.) infusions and intramuscular (i.m.) administration. Cefotaxime was well tolerated and mean peak serum levels exceeded the minimum inhibition concentration (MIC) values for a wide spectrum of potential bacterial pathogens. Approximately 48% of the i.v. doses was excreted renally; average volume of distribution was 30% of body weight and the t 1/2 was about 1 h. Cefotaxime was rapidly absorbed following i.m. injection with maximum serum concentrations occurring at approximately 0.6 h. Serum and urine antibacterial activity reflected the concentration of cefotaxime and MIC of the bacterial pathogens tested.
Cefamandole resistance in five patients was studied. Microorganisms emerged resistant to cefamandole during therapy with the drug in three patients with complicated infections. This resistance was associated with an enhanced production of beta-lactamase and/or with a change in the substrates and the isoelectric focusing patterns of the enzymes. Cross-resistance to other beta-lactam antibiotics developed concurrently in isolates from these patients. Disk diffusion tests did not detect resistance to cefamandole in the pretreatment isolate from the fourth patient; this isolate produced inactivating enzymes, and resistance was detected only in broth dilution tests. In the fifth patient, infection with a cefamandole-resistant Enterobacter developed during postoperative therapy with the drug. Resistance to cefamandole in the isolate from this patient was unstable and was associated with inducible beta-lactamase activity. These examples emphasize the need for close monitoring of patients who are given cefamandole and for thorough in vitro evaluation of isolates from the patients both before and after treatment.
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In an evaluation of the limulus lysate assay (LLA) as a method for detecting gonococcal endotoxin in cervical exudates diluted 1:800, positive LLA results were obtained from 17 of 18 patients (94%) with culture-proved gonococcal cervicitis, and negative results were obtained from 22 of 22 patients (100%) with culture-negative specimens. In vitro tests comparing the sensitivity of the LLA for Neisseria gonorrhoeae and other gram-negative organisms showed the LLA to be more sensitive in detecting N. gonorrhoeae (minimum sensitivity, 10(4) organisms per milliliter) than other commonly encountered urogenital gram-negative bacteria (minimum sensitivity, greater than 10(5) organisms per milliliter). Thus, in preliminary studies involving otherwise healthy women, the LLA appeared to correlate with bacteriologic methods for diagnosing gonococcal cervicitis and may aid in identifying nongonococcal cervicitis. In addition, the LLA was easy to perform, with test results available within an hour after the patient's initial examination.
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In an evaluation of the limulus assay as a method for detecting endotoxin in urethral exudates, positive results of urethral samples at a 1/200 dilution were obtained from 73 out of 73 patients with culture-positive gonococcal urethritis while negative results were obtained from 26 out of 27 patients with cuture-negative urethral specimens. A specimen from one patient, which gave negative results on Gram stain and culture, gave positive results to the limulus test. The overall accuracy of the limulus test for predicting culture results was 99% (p less than 0.001). Thus, in preliminary studies of otherwise healthy men, the results of the limulus assay correlated with those of biological methods for diagnosing urethral gonorrhoea; the test may, therefore, be of use in identifying cases of nongonococcal urethritis.
Endocarditis caused by Cardiobacterium hominis was observed in a penicillin-allergic patient with a prosthetic cardiac valve who had received prophylactic therapy with erythromycin for dental extractions. The organism was resistant to erythromycin and vancomycin, with minimal inhibitory concentrations of 12.5 microgram/ml and 25 microgram/ml, respectively, but was sensitive to penicillin G, tetracycline, cephalexin, and cefaclor. This case suggests that currently recommended antibiotic prophylactic therapy for endocarditis, especially in penicillin-allergic patients, may be inadequate for unusual pathogens such as C hominis.
Four patients with Bacteroides fragilis bacteremia, one patient with a brain abscess due to Bacteroides species, Fusobacterium naviforme, and Peptostreptococcus species, and an infant with Bacteroides species ventriculitis and meningitis were treated with metronidazole. In all cases the anaerobic pathogens were eradicated. Five of the six patients recovered. One patient with leukemia in whom B fragilis bacteremia was eradicated by metronidazole treatment subsequently died of Pseudomonas aeruginosa bacteremia. Ventricular fluid and serum concentrations of metronidazole were determined in the case of meningitis and are reported.
Dorsoventral thoracic radiographs of 9 dogs were taken from 0 degree to 20 degrees to the right and to the left of a vertical line from mid-sternum to the mid-thoracic vertebrae. Certain measurements indicated that angles greater than 5 degrees from the vertical introduced significant distortions of the heart shadow and thoracic wall in some instances. A method is proposed for determining from a DV thoracic radiograph when improper positioning has produced an angulation greater than 5 degrees.
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To evaluate the potential usefulness of a single large oral dose of trimethoprim-sulfamethoxazole (TMP-SMZ) for the treatment of uncomplicated genitourinary gonorrhea, the pharmacokinetics of a 12-tablet dose containing 960 mg of TMP and 4,800 mg of SMZ were studied in 15 male volunteers, and the tolerance of this regimen was compared to that of a placebo in a double-blind crossover study. Both TMP and SMZ were rapidly absorbed. Peak mean serum concentrations (+/- standard deviation) of TMP, total SMZ, and free SMZ were 9.2 +/- 2.2, 259.4 +/- 40.9, and 233.7 +/- 33.6 mug/ml, respectively. Elimination half-lives were 16.7, 14.6, and 12.9 h, respectively. When results were compared to data from similar studies after smaller doses, peak mean serum concentrations were proportional to dose, but elimination half-lives were longer after larger doses. Urinary concentrations of TMP, total SMZ, and free SMZ were many-fold higher than serum concentrations. Percents recovery (+/- standard deviation) in urine were 60.6 +/- 10.6, 80.2 +/- 7.8, and 37.4 +/- 6.5%, respectively, during the 48 h after administration. The incidence of severe headache and of objective transient oliguria was significantly higher after TMP-SMZ than after placebo. Although the observed serum concentrations of TMP and SMZ surpassed concentrations necessary to inhibit clinical isolates of Neisseria gonorrhoeae in vitro for longer than 24 h, the adverse reactions associated with a 12-tablet dose of TMP-SMZ would preclude the clinical usefulness of such a therapeutic regimen.
A standardized disk diffusion test was developed and used to test the susceptibility of 102 strains of Neisseria gonorrhoeae to combinations of trimethoprim and sulfamethoxazole (TMP/SMX) by relating zone diameters of inhibition to minimal inhibitory concentrations (MIC's). MIC's for TMP/SMX in ratios of 1:20 ranged from 0.08/1.52 to 2.5/47.5 mug/ml and zones of inhibition ranged from 34 to 10 mm. The coefficient of correlation (r) was -0.75. For comparison, a regression line was similarly calculated for ampicillin. MIC's ranged from 0.02 to 0.32 mug/ml and zones of inhibition ranged from 50 to 31 mm; r was -0.71. With establishment of MIC breakpoints to define the categories, susceptible, intermediate, and resistant, the disk duffusion test would be as reliable for estimating susceptibility of gonococci to TMP/SMX as for estimating susceptiblity to ampicillin.