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Biomedical subjects

G K Harding

Publications and source records attributed to G K Harding.

At least 73 records · Page 4Linked to original sources

Advances in the treatment of urinary tract infection.

Single dose treatment regimens are currently the treatment of choice in women with acute urethrocystitis. Women who have concomitant asymptomatic renal infections will have a recurrence and require further investigation and more conventional 14-day treatment regimens. Single dose treatment is a specific and moderately sensitive diagnostic aid for women with urinary infection. Further carefully planned studies are required to determine optimal treatment regimens for women with renal infection and men with infections originating in the kidneys or prostate.

Anti-Bacterial Agents↗

Randomized controlled trial comparing trimethoprim/sulfamethoxazole and trimethoprim for infection prophylaxis in hospitalized granulocytopenic patients.

The clinical and microbiologic efficacy of trimethoprim alone and trimethoprim/sulfamethoxazole for infection prevention was evaluated in 75 patients during 92 episodes of granulocytopenia. Ultimately, 60 patients were evaluable during 77 episodes of granulocytopenia, 36 episodes in the trimethoprim group and 41 episodes in the trimethoprim/sulfamethoxazole group. The incidence of infection was higher in the trimethoprim group (50 percent) than in the trimethoprim/sulfamethoxazole group (39 percent), but this did not reach statistical significance. Trimethoprim did not appear to be as protective as trimethoprim/sulfamethoxazole when the granulocyte count was less than 100/mm3. In patients receiving trimethoprim/sulfamethoxazole, aerobic gram-negative bacilli cleared from fecal surveillance cultures more often and new aerobic gram-negative bacilli were acquired less often than in those receiving trimethoprim alone (p less than 0.05). More myelosuppression was observed among patients receiving trimethoprim/sulfamethoxazole (p less than 0.001). These observations suggest that trimethoprim alone may not be optimal for preventing colonization and infection in granulocytopenic patients and that combination with other agents may be necessary to increase the spectrum of activity. Trimethoprim/sulfamethoxazole itself may predispose toward an increased risk of infection by prolonging myelosuppression.

Adult↗

Comparative trial of norfloxacin and trimethoprim-sulfamethoxazole in the treatment of women with localized, acute, symptomatic urinary tract infections and antimicrobial effect on periurethral and fecal microflora.

Forty-three women with acute, symptomatic urinary tract infections were randomized to receive either norfloxacin (400 mg) twice daily or trimethoprim-sulfamethoxazole (160-800 mg) twice daily for 10 days. Of the 43 patients, 7 (16%) had low-count bacteriuria and pyuria and were included in the evaluation. Escherichia coli was isolated in 72% of the infections, whereas coagulase-negative staphylococci were isolated in 14%. All isolates were susceptible to the assigned study drug. The MICs for 90% of the strains susceptible to norfloxacin and trimethoprim-sulfamethoxazole were less than or equal to 2 and less than or equal to 0.8-16 micrograms/ml, respectively. The cure rates for norfloxacin and trimethoprim-sulfamethoxazole were 95 and 90%, respectively. There were 17 patients with presumptive upper tract infections; only 1 of these relapsed after therapy. The effects on the periurethral flora were similar in both groups, but the infecting organism was eradicated from the fecal flora in 93% of the patients treated with norfloxacin and in 57% of the patients treated with trimethoprim-sulfamethoxazole. More early reinfections occurred in the trimethoprim-sulfamethoxazole group, with resistant organisms appearing in urine and in the periurethral and fecal flora in all cases. Three patients in each group experienced adverse clinical effects, but these were more severe in the trimethoprim-sulfamethoxazole group. No adverse hematological or biochemical changes were noted. From these results, we concluded that norfloxacin is at least as effective as trimethoprim-sulfamethoxazole in the therapy of acute, symptomatic urinary tract infections in women.

Acute Disease↗

Bacteriuria in elderly institutionalized men.

Over a two-year period we obtained monthly urine samples from all noncatheterized male residents on two geriatric wards to determine the occurrence and optimal management of bacteriuria in this population. Among 88 men the prevalence of bacteriuria was 33 per cent, and the incidence was 45 infections per 100 patients per year. Outcomes after single-dose therapy for asymptomatic bacteriuria with 43 courses of trimethoprim/sulfamethoxazole and 23 of tobramycin included 15 cures, 40 relapses, and 11 treatment failures. Thirty-six residents who had a relapse or in whom single-dose therapy failed were randomly assigned to receive therapy to eradicate bacteriuria or to receive no therapy. All 20 residents who received no therapy remained bacteriuric. The 16 residents who received therapy had fewer months of bacteriuria after randomization, but at the end of the study only one remained free of bacteriuria. Mortality and infectious morbidity after randomization were similar in the two groups. These data suggest that asymptomatic bacteriuria is common in elderly institutionalized men and that therapy is neither necessary nor effective.

Aged↗

Reduction in mortality from gram-negative sepsis in neutropenic patients receiving trimethoprim/sulfamethoxazole therapy.

The causes of death were reviewed in 53 patients from two prospective randomized trials on the efficacy of trimethoprim/sulfamethoxazole as prophylaxis of gram-negative bacillary infection in granulocytopenic patients. Twenty-nine deaths occurred in patients treated with TMP/SMX prophylaxis while 24 occurred in patients who served as controls in the first trial. The two groups were similar, with the exception that more patients in the TMP/SMX group had acute leukemia (82 versus 50%; P less than 0.02). Microbiologically documented gram-negative rod infection preceeded death in 8/24 control patients as compared to 2/29 TMP/SMX recipients (P less than 0.02). This decrease in gram-negative related deaths was most pronounced in the patients with acute leukemia. Fatal gram-negative rod infection occurred in 7/12 control leukemic patients as compared to 2/24 TMP/SMX treated patients. Despite the reduction in numbers of gram-negative rod-related deaths, infectious deaths accounted for 16/24 and 15/29 patients in control and TMP/SMX treated patients, respectively. Similar numbers of fungal, viral, and gram-positive bacterial infections occurred in each group. Fever with pulmonary infiltrates but without proven etilogic agents were included in the category of "clinically documented infections;" 6/7 patients with fever and undiagnosed pulmonary infiltrates were in the TMP/SMX group. Prophylactic administration or oral trimethoprim/sulfamethoxazole reduces the frequency of fatal gram-negative rod infections in neutropenic patients.

Adult↗

Comparative activities of norfloxacin and fifteen other antipseudomonal agents against gentamicin-susceptible and -resistant Pseudomonas aeruginosa strains.

We compared the activity of norfloxacin (MK-0366), a new orally absorbable derivative of naladixic acid, with those of other antipseudomonal agents against Pseudomonas aeruginosa. Norfloxacin was the most active against both gentamicin-susceptible and gentamicin-resistant strains, having 90% minimal inhibitory concentrations of 2 and 8 micrograms/ml, respectively. This excellent in vitro activity may make norfloxacin effective for oral therapy of P. aeruginosa urinary tract infections.

Anti-Bacterial Agents↗

Characterization of coagulase-negative staphylococci from urinary tract specimens.

Species of coagulase-negative staphylococci isolated from urine specimens submitted from both inpatients and outpatients to the clinical microbiology laboratory of a teaching hospital were identified with a biotyping system, with species then correlated by clinical features and antimicrobial susceptibility. Of 145 isolates, 102 (70%) were Staphylococcus epidermidis, 24 (17%) were Staphylococcus saprophyticus, 7 (4.7%) were Staphylococcus haemolyticus, 4 (2.8%) were Staphylococcus hominis, 3 (2.1%) were Staphylococcus simulans, and 5 (3.4%) were other species. Features characterizing persons with bacteriuria with S. saprophyticus compared with bacteriuria with any other species included female sex (95% versus 52%), young age (median age, 22 years versus 61 years), ambulatory status (hospital outpatients, 86% versus 23%), and absence of indwelling catheters (4.5% versus 49%). All other coagulase-negative staphylococci were isolated in a setting suggesting nosocomial acquisition, were more frequently resistant to common antimicrobial agents (42% multiply resistant versus 4.2% of S. saprophyticus), and were not distinguished by clinical features. Novobiocin susceptibility, with a sensitivity of 100% and specificity of 96%, provided a simple and reliable test for differentiation of S. saprophyticus from other coagulase-negative staphylococci and should be routinely used for urinary tract specimens in the clinical laboratory.

Anti-Bacterial Agents↗

Therapy for acute cystitis in adult women. Randomized comparison of single-dose sulfisoxazole vs trimethoprim-sulfamethoxazole.

One hundred seventeen unselected women with symptoms of acute cystitis were randomized to groups for immediate therapy with one of the following four single-dose regimens: (1) 1 g of sulfisoxazole; (2) 2 g of sulfisoxazole; (3) a combination of trimethoprim, 160 mg, and sulfamethoxazole, 800 mg; and (4) a combination of trimethoprim, 320 mg, and sulfamethoxazole, 1,600 mg. Forty-one women were excluded, 13 did not return for follow-up, and 28 did not have significant bacteriuria in the pretherapy culture. Escherichia coli was isolated in 81% of infections. Antibacterial activity was significantly greater in urine collected during the 24 hours after therapy in those who received trimethoprim-sulfamethoxazole. However, overall cure varied from 85% to 95%, without any great differences between the regimens. The rate of cure of 69% in the 13 patients with presumptive evidence of renal infection (antibody-coated bacteria present) was significantly lower than the rate of cure of 95% in women without evidence of renal infection. Single-dose therapy with these regimens was safe and effective in adult women with symptoms of acute cystitis, regardless of the localization of the site of infection.

Acute Disease↗

Clostridium difficile and cytotoxin in feces of patients with antimicrobial agent-associated pseudomembranous colitis.

Thirty patients with antimicrobial agent-associated pseudomembranous colitis (PMC) were studied for the presence of Clostridium difficile and its cytotoxin in feces. Either colonoscopy or barium enema radiography was required in three patients for the diagnosis of PMC because of nondiagnostic findings at sigmoidoscopy. Both the organism and cytotoxin were detected in 27 of the 30 patients; Staphylococcus aureus was excluded as the cause of PMC in two of the remaining patients. Eighteen of 19 patients with C. difficile-induced PMC who were treated with oral vancomycin had a salutary response; seven patients, however, had a relapse of colitis following the discontinuation of vancomycin. In general, relapses of colitis responded to retreatment with vancomycin. The implication of C. difficile as a cause of diarrhea is best achieved by the demonstration of colonic mucosal plaques or of a pseudomembrane. The value of fecal culture for C. difficile and cytotoxin assay is limited by the existence of asymptomatic carriers.

Adult↗

Chemoprophylaxis for Neisseria meningitidis in an isolated Arctic community.

Community chemoprophylaxis with a regimen of sequential minocycline/rifampin (adults) or rifampin alone (children [less than 12 years of age]) was undertaken in a remote Arctic community one year after an outbreak of meningitis due to Neisseria meningitidis serogroup B. Nasopharyngeal carriage rates of N. meningitidis before prophylaxis were 32.4% in Inuit (Eskimos) and 6% in Caucasians, with maximal carriage (44.8%) in adolescents. Serogroup B accounted for 63.9% of all isolates before prophylaxis. One week after prophylaxis, the nasopharyngeal carriage rates were 0.8% in Inuit who had received prophylaxis and 33.3% in those who had not received prophylaxis (P less than 0.005). This reduction persisted at nine weeks after prophylaxis, when carriage rates were 1.2% in those who had received prophylaxis and 22.6% in individuals who had not received prophylaxis. Of the strains obtained before prophylaxis, 7.8% were sulfadiazine-resistant, whereas 35% of all isolates obtained from prophylaxis were sulfadiazine-resistant. Rifampin- or minocycline-resistant strains were not identified either before or after prophylaxis.

Adolescent↗

The association of urinary tract infection with sexual intercourse.

To assess the significance of sexual intercourse as a precipitating factor of urinary tract infection in premenopausal women with recurrent infection, 15 patients were monitored with daily dipslides and calendar recording of intercourse episodes after antimicrobial prophylaxis was discontinued. Eleven patients experienced 16 infections; 12 infections occurred within 24 hr of an intercourse episode, two occurred during the menstrual period, and two had no recognizable association. In 12 control subjects, followed in a similar fashion, three infections--all within 24 hr of an intercourse episode--were documented. There was no difference in frequency of intercourse between patients and controls, but the frequency was higher in infected women than in uninfected women (P less than 0.02). These data suggest that in sexually active women, most urinary tract infections are intercourse-related.

Adult↗

Emergence of rifampin-resistant Haemophilus influenzae.

Rifampin susceptibility of nasopharyngeal Haemophilus influenzae strains was determined before and after community-wide chemoprophylaxis with rifampin (children) and sequential minocycline-rifampin (adults). All strains were rifampin susceptible before prophylaxis, but 10.3% of the strains at 1 week and 7.5% of the strains at 9 weeks after prophylaxis were rifampin resistant.

Drug Resistance, Microbial↗

Trimethoprim alone in the treatment and prophylaxis of urinary tract infection.

Trimethoprim was used alone to treat urinary tract infections in 20 women who were unable to tolerate sulfonamides. Of ten acute symptomatic urinary tract infections, four were cured, three were not, and three cases could not be evaluated. Two other women received trimethoprim for suppression of infection complicating stag-horn calculi. The conditions of both patients improved clinically but the urine remained infected. Eight women treated prophylactically with low-dose trimethoprim for recurrent urinary tract infection accumulated a total of 16 patient-years of prophylaxis. During treatment, the incidence of infection was 0.56 per patient-year compared with 4.25 infections in the year preceding study. Adverse reactions occurred in eight of 20 patients and administration of the drug had to be stopped in five cases. Trimethoprim alone is effective for the treatment and prophylaxis of urinary tract infections, but may cause a high incidence of adverse reactions in patients known to be sensitive to sulfonamides.

Adult↗

A comparison of the efficacy of nalidixic acid and cephalexin in bacteriuric women and their effect on fecal and periurethral carriage of enterobacteriaceae.

Eighty-one women were randomly selected for treatment with nalidixic acid (1 g four times a day) or cephalexin (500 mg four times a day) as therapy for 131 episodes of bacteriuria localized using the antibody-coated bacteria (ACB) test. Bladder infections were treated for three days and renal infections for 14 days. Rates of cure were not significantly different between treatment groups in each drug regimen. However, significantly more relapses occurred in the patients with ACB-positive infections treated for 14 days with cephalexin than in those treated for 14 days with nalidixic acid. More early reinfections occurred in the cephalexin-treated group after both three and 14 days of therapy. Resistance to nalidixic acid developed in the infecting bacteria in the urine during therapy with nalidixic acid in 3% of women after three days and in 16% of women after 14 days. Simultaneous resistance appeared in the urine, periurethral area, and fecal flora of these patients.

Antibody-Coated Bacteria Test, Urinary↗

Trimethoprim-rifampin, a new combination agent: efficacy in localized urinary infection and influence on microflora.

Twenty women with recurrent or persistent urinary tract infections were treated with a fixed combination of trimethoprim-rifampin (TMP-RAM). The site of infection was established by the antibody-coated bacteria test. Sixteen women had upper tract infections (antibody-coated bacteria tests positive); eight were cured, three failed, and five relapsed. All four women with lower tract infections (antibody-coated bacteria tests negative) were cured. Three of five patients with structural abnormalities failed. The 12 cures and 5 relapses were associated with organisms susceptible to either TMP (minimal inhibitory concentration, less than or = to 7 micrograms/ml) or RAM (minimal inhibitory concentration, less than or = to 32 micrograms/ml). In contrast, two of the three failures were associated with organisms resistant to both TMP and RAM. In one patient, RAM resistance emerged during treatment. During therapy, urinary strains were eradicated from the periurethral and anal-canal areas in all but 3 fo 16 patients. Adverse reactions, noted in 16 women, included nausea (10), dizziness (6), headaches (2), rash (1), an blurred vision (1). Antimicrobial susceptibility data on 246 isolated from urinary, periurethral, and anal-canal specimens are included. Our findings suggest that TMP-RAM is effective in urinary infections and may prevent the emergence of RAM-resistant strains.

Drug Combinations↗