Godfrey K. M. Harding

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.

A Canadian National Surveillance Study of Urinary Tract Isolates from Outpatients: Comparison of the Activities of Trimethoprim-Sulfamethoxazole, Ampicillin, Mecillinam, Nitrofurantoin, and Ciprofloxacin

ABSTRACT Ampicillin, trimethoprim-sulfamethoxazole, mecillinam, nitrofurantoin, and ciprofloxacin mean resistance rates for 2,000 urinary tract isolates collected from outpatients across Canada in 1998 were 41.1, 19.2, 14.7, 5.0, and 1.8%, respectively. ForEscherichia coli isolates alone (n = 1,681) comparable rates were 41.0, 18.9, 7.4, 0.1, and 1.2%, respectively. The majority of E. coli isolates resistant to ampicillin, trimethoprim-sulfamethoxazole, or ciprofloxacin were susceptible (MIC, <16 μg/ml) to mecillinam.

How Long Should Catheter-Acquired Urinary Tract Infection in Women Be Treated?: A Randomized Controlled Study

OBJECTIVE To determine the optimal management of catheter-acquired bacteriuria after short-term catheter use in women. PATIENTS Asymptomatic patients (119) with catheter-acquired bacteriuria were randomly assigned to receive no therapy, a single dose (320-1600 mg) of therapy with trimethoprim-sulfamethoxazole, or 10 days (160-800 mg twice daily) of therapy. Thirty-two patients with lower tract symptoms alone received a single dose or 10 days of therapy, and 10 patients with upper tract symptoms or signs received 10 days of therapy. MAIN RESULTS The mean and median durations of catheter use were 6 and 4 days, respectively. Bacteriuria resolved within 14 days without therapy in 15 of 42 (36%; 95% CI, 21% to 51%) asymptomatic patients. Seven of the remaining patients developed symptoms. Single-dose therapy resolved infection in 30 of 37 patients (81%; CI, 68% to 94%); 10 days of therapy resolved infection in 26 of 33 (79%; CI, 65% to 93%). For patients with lower tract symptoms alone, resolution rates with single-dose therapy or 10 days of therapy were similar (11 of 14 [79%] and 13 of 16 [81%], respectively). Ten days of therapy resolved infection in 6 of 9 (67%) patients with upper tract symptoms. Infection was resolved more often in women who were less than or equal to 65 years than in older women (62 of 70 [89%] versus 24 of 39 [62%]; P less than 0.001). Bacteriuria resolved spontaneously more frequently in younger (14 of 19 [74%] compared with 1 of 23 older women [4%]; P less than 0.001). Single-dose therapy resolved infection in 31 of 33 (94%) patients who were less than or equal to 65 years. CONCLUSIONS Asymptomatic bacteriuria after short-term catheter use frequently becomes symptomatic and should be treated. For asymptomatic patients and patients with lower tract symptoms alone, single-dose therapy was as effective as 10 days of therapy; it was very effective in women who were less than or equal to 65 years. Bacteriuria resolved spontaneously within 14 days after catheter removal more commonly in women who were less than or equal to 65 years and both types of therapy were less effective in older women.

A Controlled Study of Antimicrobial Prophylaxis of Recurrent Urinary Infection in Women

Abstract Twenty-seven adult women and thirteen girls with recurrent urinary infections were treated to eradicate their infection and then observed for recurrences while sequentially receiving three prophylactic drug regimens and a period with no drug therapy. The prophylactic regimens consisted of sulfamethoxazole, 500 mg daily, methenamine mandelate, 2 g daily, together with ascorbic acid 2 g daily, or trimethoprim, 40 mg, in combination with sulfamethoxazole, 200 mg daily. Children received half the adult doses. Thirty-three infections (3.6 per patient-year) occurred in patients on no drug therapy, 22 (2.5 per patient-year) in those taking sulfamethoxazole, 13 (1.6 per patient-year) in those taking methenamine mandelate and ascorbic acid, and 1 (0.1 per patient-year) in those taking trimethoprim–sulfamethoxazole. Trimethoprim–sulfamethoxazole was also the most effective in preventing colonization of the periurethral area with enterobacteriaceae. These results suggest that a daily low dose of trimethopri...

Febrile urinary infection in the institutionalized elderly

PURPOSE Bacteriuria is common among institutionalized elderly populations, but the contribution of urinary infection to febrile morbidity is unknown because of difficulties in clinical ascertainment. This study was undertaken to febrile morbidity using both clinical and serologic criteria. METHODS Episodes of fever in residents of two long-term care institutions were identified prospectively for 2 years. Serum and urine specimens were obtained initially and at 4 weeks. The proportion of episodes attributable to urinary infection was determined by both standard clinical criteria proposed for use in these populations and serum antibody response to uropathogens. RESULTS For 372 fewer episodes, 211 met clinical criteria for infection: 147 (40%) of the respiratory tract; 26 (7%) of the genitourinary tract; 25 (6%) of the gastrointestinal tract; and 13 (3%) of skin and soft tissue. Of the remaining 161 fever episodes, 2 (1%) were noninfectious and 159 (43%) were of unknown origin. The prevalence of bacteriuria for residents with nongenitourinary sources of fever varied from 32% to 75%. An antibody response meeting serologic criteria for urinary infection occurred in 26 (8.3%) of 314 episodes with paired sera obtained; 10 (43%) of 23 identified clinically as genitourinary infection, 14 (11%) of 132 unknown, 1 (4%) of 25 gastrointestinal, and 1 (0.8%) of 122 respiratory. The positive predictive value of bacteriuria for febrile urinary infection identified by clinical criteria was was 11% (95% confidence interval [CI] 4%, 18%) and identified by serologic criteria was 12% (95% CI 7%, 17%). CONCLUSIONS Urinary infection contributes to less than 10% of episodes of clinically significant fever in this high-prevalence bacteriuric population. A restrictive clinical definition for genitourinary infection has poor sensitivity and specificity compared with serologic criteria for identification of fever of urinary source, and bacteriuria has a low predictive value for identifying febrile urinary infection.

The Association of Bacteriuria with Resident Characteristics and Survival in Elderly Institutionalized Men

Ninety-one elderly male residents of a skilled nursing facility were classified as nonbacteriuric (41%), intermittently bacteriuric (34%), or continuously bacteriuric (25%) on the basis of urine cultures obtained over a 3-year period. Bacteriuric and nonbacteriuric residents were similar in age, number of diagnoses and medications, and mobility. However, bacteriuric residents were more frequently confused or demented, whether continuously bacteriuric (78%) or intermittently bacteriuric (62%) compared with nonbacteriuric residents (42%) (p less than 0.04). In addition, bacteriuria was significantly associated with incontinence of bladder (96% of continuous, 66% of intermittent, and 25% of nonbacteriuric; p less than 0.001) and bowel (52%, 39%, and 5.5%, respectively; p less than 0.002). At 6 years of follow-up there were no differences in survival among the three groups. Urinary tract infection caused or contributed to only two (2.9%) deaths. Thus, in this population, bacteriuria was associated with higher functional disability but not with increased mortality.

Antibiotic Pharmacodynamics in Surgical Prophylaxis: an Association between Intraoperative Antibiotic Concentrations and Efficacy

ABSTRACT The objective of this study was to characterize the relationship between gentamicin concentrations during surgery and the development of wound infection following colorectal operations. Despite decades of research in surgical prophylaxis, the relationship between intraoperative antibiotic concentrations and postoperative infection and the concentrations required for effective prophylaxis have not been established. A pharmacodynamic analysis was conducted using data from a previous prospective, randomized, double-blind clinical study which compared two dosage regimens of gentamicin plus metronidazole for prophylaxis in connection with elective colorectal surgery. Univariate and multivariate analyses of risk factors for postoperative wound infection were conducted, and the relationship between intraoperative gentamicin concentrations and surgical outcome was characterized. The gentamicin concentration at the time of surgical closure was one of the strongest independent risk factors for infection (P = 0.02), along with the presence of diabetes mellitus (P = 0.02), stoma (P = 0.04), and advanced age (P = 0.05). Gentamicin concentrations at closure of less than 0.5 mg/liter were associated with an infection rate of 80% (representing 8 of 10 patients with concentrations below that level) (P = 0.003). Receiver operating characteristic curve analysis identified a critical closure concentration of 1.6 mg/liter for effective surgical prophylaxis (P = 0.002; sensitivity, 70.8%; specificity, 65.9%). This study provides new and important information on antibiotic pharmacodynamics in surgical prophylaxis. It demonstrates the critical effect of the antibiotic concentration at closure on wound infection and suggests a significant association between the concentration and other well-established risk factors, like the timing of preoperative antibiotic administration and surgery duration.

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.

The Postantibiotic Effect: A Review of in Vitro and in Vivo Data

The term postantibiotic effect (PAE) refers to a period of time after complete removal of an antibiotic during which there is no growth of the target organism. The PAE appears to be a feature of most antimicrobial agents and has been documented with a variety of common bacterial pathogens. Several factors influence the presence or duration of the PAE including the type of organism, type of antimicrobial, concentration of antimicrobial, duration of antimicrobial exposure, and antimicrobial combinations. In vitro, beta-lactam antimicrobials demonstrate a PAE against gram-positive cocci but fail to produce a PAE with gram-negative bacilli. Antimicrobials that inhibit RNA or protein synthesis produce an in vitro PAE against gram positive cocci and also produce a PAE against gram-negative bacilli. In vitro methods used to determine the PAE include colony counts, optical density, and measurement of adenosine triphosphate in bacteria. The exact mechanisms by which antimicrobials induce the PAE have not been clearly delineated. Animal studies reveal in vivo PAEs in accordance with PAEs obtained in vitro for most organism/ antimicrobial combinations. The clinical relevance of the PAE is probably most important when designing dosage regimens. The presence of a long PAE allows aminoglycosides to be dosed infrequently; the lack of an in vivo PAE suggests that beta-lactam antimicrobials require frequent or continuous dosing. Important questions remain to be answered concerning the PAE.

A Prospective, Randomized Trial of 3 or 14 Days of Ciprofloxacin Treatment for Acute Urinary Tract Infection in Patients with Spinal Cord Injury

BACKGROUND Urinary tract infection (UTI) is common among patients with spinal cord injury. The optimal duration of treatment for symptomatic UTI has not been determined. METHODS A randomized, double-blind, placebo-controlled trial compared 3-day and 14-day regimens of ciprofloxacin, 250 mg twice daily, for the treatment of acute UTI in patients with spinal cord injury. Patients with pyelonephritis, struvite stones, hydronephrosis, or long-term indwelling catheters were excluded from the trial. RESULTS Sixty patients with spinal cord injury were enrolled in the trial, with 30 patients assigned to each study arm. The most common infecting organisms were Klebsiella species (30%), Enterococcus species (22%), and Escherichia coli (22%); 33% of the infections were polymicrobial. Microbiological cure at long-term follow-up was significantly better among patients who received therapy for 14 days than among patients who received therapy for 3 days. By 6 weeks of follow-up, microbiological relapse (in 11 [37%] of 30 patients vs. 2 [7%] of 30 patients; 95% confidence interval [CI], 1.38-3.18; P=.01) and symptomatic relapse (in 7 [23%] 30 patients vs. 0 of 30 patients; 95% CI, 1.69-3.13; P=.01) both occurred more frequently in patients treated for 3 days. Reinfection occurred with similar frequency in patients in the 2 study arms. Six of 7 evaluable patients with treatment failure had a fluoroquinolone-resistant organism isolated at enrollment. CONCLUSIONS For patients with spinal cord injury, treatment of acute symptomatic UTI for 14 days leads to improved clinical and microbiological outcomes, compared with short-course therapy.