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Biomedical subjects

G K Harding

Publications and source records attributed to G K Harding.

At least 91 records · Page 5Linked to original sources

Prospective, randomized comparative study of clindamycin, chloramphenicol, and ticarcillin, each in combination with gentamicin, in therapy for intraabdominal and female genital tract sepsis.

The results of a prospective, randomized comparative study of the efficacy and toxicity of clindamycin, chloramphenicol, and ticarcillin in the treatment, concomitantly with gentamicin to ensure complete aerobic coverage, of 175 patients with serious mixed aerobic/anaerobic intraabdominal or female genital tract sepsis are reported. In the group with intraabdominal sepsis, 33 (79%) of 42 treated with clindamycin, 43 (81%) of 53 treated with chloramphenicol, and 35 (90%) of 39 treated with ticarcillin were cured. In the group with genital tract sepsis, 16 (94%) of 17 treated with clindamycin, 11 (100%) of 11 treated with chloramphenicol, and 12 (92%) of 13 treated with ticarcillin were cured. Diarrhea occurred most frequently in patients treated with clindamycin (P < 0.001), hematologic suppression occurred most frequently in patients treated with chloramphenicol (P < 0.01), and hypokalemia occurred most frequently in patients treated with ticarcillin (P < 0.01). Clindamycin, chloramphenicol, and ticarcillin, each in combination with gentamicin, are equally effective in therapy for intraabdominal or female genital tract sepsis.

Abdomen↗

Role of cervicovaginal antibody in the pathogenesis of recurrent urinary tract infection in women.

Introital colonization with Enterobacteriaceae is considered to be one of the principal predisposing factors to recurrent urinary tract infections (UTI) in adult females. One proposed mechanism allowing introital colonization in these patients is the absence of local cervicovaginal antibody. To test this hypothesis, we examined cervicovaginal washings from 22 patients with a history of recurrent UTI and 29 normal controls with no history of UTI for specific local antibody by using indirect immunofluorescence. No significant difference in antibody was found in these populations. Fourteen percent (3/22) of the patients had antibody to their introital Escherichia coli and 34% (10/29) of the controls had antibody to their fecal E. coli. Consequently, a sensitive radioimmunoassay technique was developed to detect cervicovaginal antibody. A solid phase was prepared by coupling to Sepharose 4B a pool of eight serogroups of E. coli which are frequently implicated in UTI. Serial dilutions of cervicovaginal washings were reacted with the solid phase, and the absorbed anti-E. coli antibodies were detected by the uptake of (125)I-labeled anti-human immunoglobulin G (IgG) or anti-human IgA. The antibody levels were quantitated by interpolation on a standard curve prepared by using immunospecifically purified human anti-E. coli antibodies. IgG and IgA levels were measured in washings from 10 colonized patients, 13 non-colonized patients, and 12 controls. There were no significant differences in IgG and IgA levels in cervicovaginal washings among the three groups. In these studies, introital colonization was not related to cervicovaginal antibody.

Antibodies, Bacterial↗

Group C streptococcal meningitis in an adult. Probable acquistion from a horse.

Although group C streptococci are infrequent pathogens in man, they commonly cause disease in animals. Only recently have they been recognized as a causative agent in meningitis in man. To our knowledge, no previous report has documented a source for the infection. We treated a previously healthy young adult with group C streptococcal meningitis, who responded rapidly to antibiotic therapy. The same species (Streptococcus zooepidemicus) that was isolated from the CSF of the patient also grew from the pharynx of the patient's horse.

Adult↗

Prophylaxis of recurrent urinary tract infection in female patients. Efficacy of low-dose, thrice-weekly therapy with trimethoprim-sulfamethoxazole.

Thirty-two women with recurrent urinary tract infections were treated after eradication of existing infections with a mixture of 40 mg of trimethoprim and 200 mg of sulfamethoxazole thrice weekly at bedtime for six months. Six preadolescents received one half this dose. During 21.3 cumulative patient-years of prophylaxis, one infection due to Streptococcus faecalis and one due to a sulfamthoxazole-and trimethoprim-sensitive Escherichia coli occurred--an infection incidence of 0.1 per patient-year. During prophylaxis, 61 of 72 periurethral cultures and 24 of 51 anal canal cultures failed to yield Enterobacteriaceae. One patient had transient colonization with a trimethoprim-resistant E coli during prophylaxis. Twenty-one patients had recurrent infection within six months of discontinuation of prophylaxis, with a mean time to recurrence of 2.6 months. One infection recurred 26 weeks following prophylaxis with a Proteus mirabilis. Thrice-weekly trimethoprim-sulfamethoxazole therapy was effective for prophylaxis of recurrent urinary tract infections and did not predispose to colonization or infection with trimethoprim-resistant Enterobacteriaceae.

Adolescent↗

Clinical efficacy and toxicity of netilmicin in the treatment of gram-negative infections.

Netilmicin, a new semisynthetic aminoglycoside antibiotic, was used to treat 41 infections in 38 patients. The outcome of four infections could not be evaluated: two patients received inadequate therapy and two did not have gram-negative infections. Clinical improvement occurred in 36 (97%) of the 37 gram-negative infections, and bacteriologic cure occurred in 30 (86%) of the 35 evaluable infections. Therapeutic serum concentrations of netilmicin were readily achieved by both intramuscular and intravenous routes. Reversible ototoxic effects occurred in 1 (3%) of 35 courses of therapy evaluated, reversible nephrotoxic effects occurred in 5 (14%) of 36 courses and mild reversible alterations in liver function occurred in 3 (19%) of 34 courses. Netilmicin appears to be effective and safe in the treatment of aerobic gram-negative infections.

Adolescent↗

A prospective controlled investigation of prophylactic trimethoprim/sulfamethoxazole in hospitalized granulocytopenic patients.

Oral trimethoprim/sulfamethoxazole (TMP/SMZ) therapy was investigated in the prophylaxis of infections in granulocytopenia. Hospitalized granulocytopenic patients were allocated at random to receive TMP/SMZ (group 1) or to a control group (group 2). The percentage of febrile granulocytopenic days was significantly reduced in group 1, 19 per cent compared to 39 per cent in group 2 (P less than 0.01). In group 1, there were no bacteremias in 59 episodes of granulocytopenia (909 days). In group 2, there were nine bacteremias in 52 episodes of granulocytopenia (796 days)(P = 0.001). Disseminated candidiasis developed in two patients in each group. Candida occurred in similar numbers in surveillance cultures in both groups; Staphylococcus aureus and Pseudomonas aeruginosa were slightly decreased, and Enterobacteriaceae resistant to TMP slightly increased in group 1. This study suggest that oral prophylactic TMP/SMZ therapy is an effective, well tolerated, easily administered alternative to "gut sterilization" with nonabsorbable antibiotics.

Acute Disease↗

Influence of mucoidy on antibody coating of Pseudomonas aeruginosa.

Antibody-coated bacteria were found in only two of 34 urine sediments from 19 catheterized patients infected with a single epidemic strain of Pseudomonas aeruginosa, whereas 12 of 19 urine sediments from 16 outpatients contained antibody-coated P. aeruginosa. In urine sediments, individual cells and microcolonies of the epidemic strain of P. aeruginosa were enclosed in ruthenium red (polysaccharide)-positive material. This strain was extremely mucoid when grown in a liquid medium for enhancement of mucoid formation. Renal infections was present in some patients, as determined by the bladder washout test and by titers of antibody in serum, and antibody was present in the urine but not coating P. aeruginosa. We conclude that the mucoid layer interfered with antibody coating of the epidemic strain of P. aeruginosa.

Antibodies, Bacterial↗

Biotyping of Escherichia coli by a simple multiple-inoculation agar plate technique.

A nine-test system using multiple-inoculation agar plates for biotyping of Escherichia coli is described. Testing of 959 strains resulted in 78 biotypes. On repeated testing, 96% of 182 strains had identical biotypes or differed by only one test. This system provides satisfactory differentiation among strains and is reproducible. Precise standardization of inoculum size is not required. Multiple inoculation allows time and cost-efficient testing of large numbers of strains.

Adult↗

Prolonged outbreak of nosocomial urinary tract infection with a single strain of Pseudomonas aeruginosa.

Sixty-six hospitalized patients became infected with a single strain of multiply resistant Pseudomonas aeruginosa over a 22-month period. The catheterized urinary tract was the site of the infection in 59 patients (89%). The outbreak was confined to a urology ward until an infected patient from this ward spent 2 weeks in the surgical intensive care unit (SICU). Subsequently patients who acquired the infection in the SICU were discharged to surgical wards throughout the hospital. Urine measuring containers and urometers used in the SICU were the reservoir of the P. aeruginosa; daily sterilization of this equipment terminated the outbreak. Urometers appeared to be the reservoir of the epidemic strain in subsequent outbreaks. Five patients were still infected when they were readmitted 3 to 12 months after the first admission, and therefore represented an additional reservoir of infection.

Cross Infection↗

Urinary tract infection localization in women.

The site of urinary infection in 51 adult women was determined by the bladder-washout technique (BW). Of the 37 patients with proved upper-tract infection shown by BW, 16 had upper-tract symptoms, three had lower-tract symptoms, and 18 were asymptomatic; 31 had antibody-coated bacteria (ACB), and six had no ACB. Of 14 patients with proved lower-tract infection shown by BW, three had upper-tract symptoms, five had lower-tract symptoms, and six were asymptomatic; none had ACB. All 31 women whose infecting bacteria were coated with antibody proved to have an upper-tract infection shown by BW. A subset of the population of adult women with upper-tract infection have organisms emanating from their ureters at BW localization, which are not coated with antibody. Physicians must be cautious in interpreting results that are negative for ACB.

Adult↗

Granulocytopenia in hospitalized patients: I. Prognostic factors and etiology of fever.

The clinical course of 126 hospitalized patients during 192 episodes of granulocytopenia and fever was studied. Fever was a regular accompaniment of granulocytopenia, occurring in 94 per cent of granulocytopenic episodes. The mean duration of granulocytopenia (less than 1,000/mm3) was 18 days, with fever (temperature greater than 38 degrees C) being present during 44 per cent of those days. Fever was present during 69 per cent of days with a granulocyte count less than 10/mm3. A presumed infection was present in 86 of 128 febrile granulocytopenic episodes in adults and in 19 of 64 febrile granulocytopenic episodes in children. A fungal infection was found in 11 patients; a viral infection in 23 patients. Bacteremia occurred during 44 granulocytopenic episodes with 16.8 bacteremias/1,000 days of granulocytopenia in adults and 12.7 bacteremias/1,000 days in children. The mortality was 33 per cent per granulocytopenic episode in adults and only 8 per cent per episode in children.

Adolescent↗

Granulocytopenia in hospitalized patients. II. A prospective comparison of two antibiotic regimens in the empiric therapy of febrile patients.

The results of empiric antibiotic therapy in 126 hospitalized patients with fever during 192 episodes of granulocytopenia were studied. Febrile granulocytopenic patients were randomly allocated to receive either carbenicillin, methicillin and gentamicin, or carbenicillin and cephalothin. The response rate for the two antibiotic regimens was similar, 49 (60 per cent) of 81 responded to the former and 42 (54 per cent) of 78 to the latter. The response rate in patients receiving other antibiotics because of specific indications or counterindications was 19 (58 per cent) of 33. Thirty-nine (35 per cent) of 110 patients who responded to initial antibiotic therapy had an increase in circulating granulocytes of one log10 or more compared to only 10 (12 per cent) of 79 nonresponders with such an increase. The mortality rate in adult patients receiving carbenicillin, methicillin and gentamicin was eight (16 per cent) of 51, compared to 18 (37 per cent) of 49 in those receiving cephalothin and carbenicillin (P less than 0.05). The significance of this difference in the initial response rate or mortality rate between patients treated with the two antibiotic regimens when only patients with documented bacterial infection were considered. Patients who responded to their initial antibiotic regimen, and patients for whose fever no explanation was found, had the best prognosis.

Adolescent↗

Anaerobic and aerobic urethral flora in healthy females.

We characterized the aerobic and anaerobic urethral flora of five healthy females by performing urethral and midstream urine cultures once weekly for 8 weeks. Aerobic cultures were performed monthly for an additional 3 months. Lactobacillus spp. were isolated from 52 of 57 samples, Staphylococcus epidermidis from 42 of 57, Corynebacterium spp. from 26 of 57, and alpha-hemolytic streptococci from 14 of 57. Two subjects had E. coli serogroup O6 and group B streptococci isolated on five occasions, respectively. Anaerobes were isolated from 32 of 35 urethral urines (91%). Bacteroides melaninogenicus accounted for 46% of these isolates. The anaerobic urethral flora varied slightly from week to week, and a similar anaerobic flora was isolated from the introitus, fourchette, and cutaneous perineum. In addition, anaerobes were isolated from 16 of 18 healthy females who had a urethral urine sample cultured once only, and B. melaninogenicus was the most frequent isolate. Of the 21 B. melaninogenicus isolates identified to subspecies, 14 were subsp. intermedius.

Adolescent↗

Bacteremia due to Bacteroidacceae: a review of 92 cases.

The clinical courses of 92 patients who had bacteremia due to Bacteroidaceae were reviewed. The overall mortality rate was 21% (19 patients). There was no significant difference between mortality rates when patients were grouped by anticipated clinical course of underlying disease (nonfatal, ultimately fatal, and rapidly fatal) and when they were grouped by type of antibacterial therapy (appropriate, including clindamycin, chloramphenicol, lincomycin, and carbenicillin; or inappropriate, signifying no antibiotic treatment or treatment with antibiotics other than the four listed above). However, there was a correlation between recovery of the patient and portal of entry of the infectious agent; patients whose source of infection was the gastrointestinal tract had a mortality rate of 29% (17 of 58 patients), whereas there were no deaths among the 26 women whose presumed source of bacteremia was the genital tract. Increasing age appeared to be an important factor as well; 17 of 19 deaths occurred in patients who were older than 40 years. There was no significant difference between the mortality rate of patients who were treated with clindamycin (15%, eight of 52 patients) and that of patients who were treated with chloramphenicol (44%, four of nine).

Adult↗

Amoxicillin therapy of acute urinary infections in adults.

Fifty-two patients, 48 females and 4 males, with suspected urinary infection were treated with amoxicillin. Twenty-two females with presumed bladder infection were treated with amoxicillin, 250 mg three times a day for 7 days; 26 females and 4 males with presumed renal infection were treated with amoxicillin, 500 mg three times a day for 14 days. Five patients were immediate treatment failures, with positive urine cultures during therapy. All five patients had been infected with amoxicillin-resistant urinary pathogens. Three patients, treated as for bladder infections, reinfected during 6 weeks of follow-up, and only one relapsed. Two patients, treated as for renal infections, reinfected, whereas four relapsed. During therapy, amoxicillin-susceptible gram-negative rods were eradicated from the periurethral area in all but one patient. Of 28 patients studied, 19 acquired a predominant growth of either resistant aerobic gram-negative rods or Candida albicans from periurethral cultures. Our findings suggest that these two regimens of amoxicillin achieve satisfactory cure rates in urinary infection, but both regimens significantly alter the normal periurethral flora.

Acute Disease↗

Characterization of bacteroides melaninogenicus.

Fifty-eight human isolates of Bacteroides melaninogenicus, 42 from a variety of clinical infections and the rest from normal flora, were studied for pigment production and ultraviolet light fluorescence and by forty biochemical and other tests, including end-product analysis by gas-liquid chromatography. In a number of instances, tests were repeated several times and the results were reproducible. Agar plate dilution susceptibility tests were also performed to 12 antimicrobial agents. These 58 strains could be reliably placed into three groups, corresponding to the three subspecies described, based on seven characteristics. These included acid production in peptone-yeast-glucose medium, production of n-butyric acid from peptone-yeast-glucose medium, esculin hydrolysis, starch hydrolysis, indole production, effect on milk, and lipase production. Production of hydrogen gas in peptone-yeast-fructose medium may be another distinguishing characteristic. In general there was not much difference in the susceptibility of the three groups to the various antimicrobial agents tested. Two strains had a minimal inhibitory concentration of penicillin G of 16 and 32 U/ml, respectively. Three strains did not produce a black pigment in spite of prolonged incubation on blood-containing media.

Anaerobiosis↗

Trimethoprim-resistant Enterobacteriaceae in urinary tract infection.

The incidence of trimethoprim-resistant Enterobacteriaceae has not increased since the introduction of the combination trimethoprim-sulfamethoxazole (TMP-SMX) into the clinical use at our centre in 1973. Using the minimum inhibitory concentration (MIC) as the index of trimethoprim resistance, this ranged from 1.6 to 800 mug/ml; for the majority of isolates it lay between 1.6 and 12.5 mug/ml. About half of these trimethoprim-resistant organisms were sensitive to sulfonamide. In vitro data suggest that organisms resistant to sulfonamide as well as to trimethoprim, where the MIC for the former drug is 3.1 mug/ml or less, will be susceptible to the combination. More resistant organisms, i.e., those for which the MIC of trimethoprim is 6.2 mug/ml or more, often appear quite resistent to the combination. There is no evidence that previous therapy with TMP-SMX is a significant predisposing factor to infection with these organisms, although there is a significant correlation between previous TMP-SMX therapy and infection with organisms with a high level of trimethoprim resistance. Organisms harbouring R-factor resistance or thymine-dependent mutants were not encountered during the course of this study.

Drug Combinations↗