Urinary antibody level and survival in bacteriuric institutionalized older subjects.

OBJECTIVE: In a previous study, elevated urine antibody levels in institutionalized subjects with asymptomatic bacteriuria were associated with decreased survival. This study was undertaken to confirm the previous observation in a prospective study in a larger cohort and to explore selected other variables that may be associated with survival. DESIGN: A prospective, 24-month, observational cohort study. SETTING: Three large nursing homes in Winnipeg, Manitoba. PARTICIPANTS: Permanent residents were identified by initial screening urine cultures and subjects with bacteriuria were enrolled. The median age of subjects was 76 years, 51% were women, and the median duration of residence before enrollment was 26 months. Subjects were highly functionally impaired. MEASUREMENTS: Monthly urine specimens were collected for culture, leukocyte count, and urine antibody. Serum specimens for antibody to uropathogens and IL6 were obtained at enrollment and every 6 months. Anthroporphometric tests of nutritional status and functional and mental status were also measured every 6 months. Residents were stratified as having elevated or not elevated urine antibody, based on the initial urine specimen. The mean urine antibody for all of each subject's specimens was also calculated, and subjects were stratified as low, intermediate, or elevated urine antibody. Outcomes measured included mortality, infection and antibiotic use, and functional, mental, and nutritional decline. RESULTS: Ninety-eight bacteriuric subjects were enrolled in the study; 34 (35%) had elevated urine antibody and 64 (65%) had not elevated urine antibody. The two groups did not differ in demographic features, co-morbidities, functional status, medication use, or infecting organisms. Survival was significantly (P < .001) poorer in the group with elevated urine antibody. At 24 months, 35% of subjects with an elevated urine antibody were alive compared with 75% with a low urine antibody level. This survival difference was consistent when the two groups were stratified by sex, institution, and presence of a chronic indwelling catheter. Subjects with elevated urine antibody had no evidence for accelerated functional or nutritional decline during the study period compared with the group with low urine antibody. These subjects did, however, have an increased incidence of episodes of symptomatic urinary infection and infections at non-urinary sites. CONCLUSIONS: Older, bacteriuric, institutionalized subjects with elevated urine antibody had decreased survival rates compared with subjects with lower urine antibody levels. There is no clinical evidence to support accelerated decline caused by chronic infection to explain this observation. Urine antibody may be a marker for immune dysregulation, which precedes death in older impaired subjects.

Erythromycin-resistant group G streptococci in an isolated northern Canadian community.

The susceptibility of groups A, C, and G streptococci isolated from pharynx or skin in two northern Canadian native communities during a one year study of the epidemiology of streptococcal infection was determined for penicillin, erythromycin and clindamycin using an agar dilution method. Organisms studied included 725 group A, 82 group C, and 184 group G streptococci. All organisms were susceptible to penicillin (minimum inhibitory concentration [MIC] range less than 0.004 to 0.015 µg/mL; MIC(90) 0.015 µg/mL) and clindamycin (range 0.007 to 0.06 µg/mL; MIC(90) 0.06 µg/mL) with no differences observed between streptococcal groups. For erythromycin, groups A and C were generally susceptible (range less than 0.007 to 0.030 µg/mL; MIC(90) 0.03 µg/mL; and range 0.007 to 1.0 µg/mL; MIC(90) 0.06 µg/mL, respectively). Group G was less susceptible (range 0.007 to greater than 2.0 µg/mL; MIC(90) greater than 2.0 µg/mL) with 38% of all isolates having an MIC greater than or equal to 1 µg/mL. On review of group G isolates, 100 of 100 from one community were susceptible (MIC less than 0.007 to 0.03 µg/mL) and 73 (87%) of 84 from the second community were resistant. All resistant strains tested were type T16. These data suggest that erythromycin-resistant group G streptococci may occur with high prevalence in certain populations and that patterns of antimicrobial susceptibility in isolated communities may be highly community-specific.

Comparison of norfloxacin versus nalidixic acid in therapy of acute urinary tract infections.

Thirty-seven adult patients with acute urinary tract infections (UTI) were randomized to receive either a seven day (lower UTI) or a 14 day (upper UTI) course of norfloxacin 400 mg orally twice daily, or nalidixic acid 1 g orally four times per day. Mean age, underlying disease and infecting organisms were similar in the two groups. Nine patients in the norfloxacin group and seven in the nalidixic acid group had presumptive evidence of upper UTI. Overall, 12 patients had antibody-coated bacteria-positive infections. The infecting organisms were: Escherichia coli (27), coagulase-negative staphylococci (four), Citrobacter freundii (three), Klebsiella pneumoniae (three), and Proteus mirabilis, Proteus vulgaris, Pseudomonas aeruginosa, Enterobacter agglomerans, Streptococcus agalactiae, Enterococcus faecalis (one of each). All of the organisms were susceptible to norfloxacin, while 81% were susceptible to nalidixic acid. The effects on the periurethral and anal canal flora were similar in both groups. Five patients in each group experienced adverse clinical effects. The cure rates for norfloxacin and nalidixic acid were 79 and 83%, respectively. There were two failures, two relapses and four reinfections in the norfloxacin group. In the nalidixic acid group, there were two failures, one relapse and four reinfections. One of the failure patients in the nalidixic acid group developed resistance to the drug, and two of the four reinfections were due to organisms resistant to nalidixic acid. In this patient population it was concluded that nalidixic acid may be as effective as norfloxacin in the treatment of acute, symptomatic UTI.

The effect of a fitness program on health status and health care consumption in Medicare MCOs.

This study examined the effect of a fitness program for Medicare MCOs on health status and health care utilization of participants. An evaluation compared outcome measures between high-level and low-level participants of the program. High-level participants scored higher on the Health Outcomes Survey and also had fewer doctor visits during the program period compared with low-level participants. The authors conclude that elderly individuals who participated at the high-level rate in a targeted fitness program maintained or improved health status and had fewer outpatient visits compared with the low-level participants. Medicare MCOs may improve health and manage costs for members by employing similar interventions focusing on functional health through exercise.

Comparative in vitro activity of norfloxacin against urinary tract pathogens.

The in vitro activity of norfloxacin (MK366) against 477 aerobic gram-negative and gram-positive clinical isolates was compared to that of nalidixic acid, nitrofurantoin, ampicillin, cephalexin, trimethoprim, sulfamethoxazole, and the combination trimethoprim-sulfamethoxazole. Norfloxacin was more active than the other agents against all gram-negative organisms tested. Minimal inhibitory concentrations (MICs) of Pseudomonas aeruginosa were less than or equal to 0.125-32 mg/l with 90% inhibited (MIC90) by 4 mg/l; MICs of the Enterobacteriaceae including Serratia marcescens were less than or equal to 0.125-8 mg/l with an MIC90 of less than or equal to 4 mg/l. There was also excellent activity against the gram-positive cocci including Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus saprophyticus and the enterococci, with MICs less than or equal to 0.125-4 mg/l and an MIC90 less than or equal to 4 mg/l. Only 8 of 477 organisms were norfloxacin-resistant (MIC greater than or equal to 16 mg/l): 3 of 100 Pseudomonas aeruginosa, 3 of 10 Pseudomonas maltophilia and 2 of 15 Streptococcus bovis strains. In contrast, 97% of the gram-positive cocci and 49% of the gram-negative bacilli were nalidixic acid-resistant (MIC greater than or equal to 32 mg/l). Norfloxacin shows excellent activity against a wide range of bacteria and merits further study as a urinary antibacterial agent.

Group A streptococcal pharyngeal carriage, pharyngitis, and impetigo in two northern Canadian native communities.

The prevalence of pharyngeal carriage of group A streptococci, streptococcal pharyngitis, and impetigo was determined in schoolchildren in two northern communities, one Inuit (mean number of schoolchildren surveyed, 233) and one native Indian (mean number of schoolchildren surveyed, 349). At three surveys from November 1984 to May 1985, pharyngeal group A streptococcal carriage was 5.3%, 22%, and 34% in the Inuit community and 5.3%, 5.1% and 10% in the native Indian, with impetigo prevalence 1.6%, 3.8% and 1.0%, and 2.4%, 4.2% and 0.6%, respectively. Increased pharyngeal carriage correlated with the increasing number of household residents and the lower school grade. In 12 months of observation the incidence of group A streptococcal pharyngitis was 49/100 schoolchildren for the Inuit and 9.4/100 for the native Indian community, with impetigo 13/100 and 11/100 respectively. The maximal incidence of pharyngitis was late winter in the Inuit community and midsummer in the native Indian. The incidence of impetigo peaked in January for both communities. M and T typing showed consecutive outbreaks of different serotypes in the Inuit community, but a persistent low level of endemic infection in the Indian community. These observations suggest a seasonal prevalence of group A streptococcal pharyngeal carriage consistent with other North American populations, but marked inter-community variation in pharyngeal carriage and disease. The midwinter peak of impetigo appears unique to these populations.

Is ingestion of milk-associated bacteria by premature infants fed raw human milk controlled by routine bacteriologic screening?

Expressed human milk is often used to feed premature infants. Raw milk contains bacteria which may be a source of infection. Milk banks have developed screening programs which combine periodic quantitative milk cultures with arbitrary rules specifying limits of bacterial concentration. It is unknown whether such programs succeed in preventing infants from being fed milk containing bacteria. At the Health Sciences Centre (Winnipeg, Manitoba, Canada), milk is screened once weekly. When a woman's milk is found to have excess bacteria, it is discarded only if she is an unrelated donor (as opposed to an infant's mother). To assess the effectiveness of this screening program, we determined the frequency at which infants fed raw human milk were exposed to milk-associated bacteria and compared the bacterial contents of donor and maternal milk. From February 1986 to April 1987, all human milk fed to 98 premature infants during the first 2 weeks of feeding (n = 10,128 feeds) was cultured quantitatively. Among study infants, 100% were exposed at least once to coagulase-negative staphylococci, 41% were exposed to Staphylococcus aureus, and 64% were exposed to gram-negative bacilli. The proportions of feeds containing bacteria and the quantities (log10 CFU [mean +/- standard deviation]) ingested per positive feed were: 39% and 5.9 +/- 0.5 for coagulase-negative staphylococci; 2.4% and 5.1 +/- 1.0 for S. aureus; and 5.2% and 4.8 +/- 1.1 for gram-negative bacilli. There were no adverse events attributable to ingestion of milk-associated bacteria. Milk coagulase-negative staphylococcal isolates were multiply antibiotic susceptible, whereas infant isolates were antibiotic resistant. Donor milk was significantly less likely than maternal milk to contain coagulase-negative staphylococcal species in any quantity (40 versus 93% of samples, respectively [P < 0.001]) or in concentrations exceeding 10(8) CFU/liter (3 versus 27% of samples, respectively [P < 0.0001]). There was no difference between milk from either source in terms of S. aureus or gram-negative bacterial content (4 to 6%). These results suggest that the Health Sciences Centre screening program is effective in limiting the number of harmless coagulase-negative staphylococcal species but has no impact on the quantity of potentially pathogenic bacteria ingested by premature infants. Implications for screening donor milk are discussed.

Prospective, randomized, placebo-controlled trial of norfloxacin for the prophylaxis of recurrent urinary tract infection in women.

Thirty women were randomized in a double-blind, placebo-controlled study to receive either norfloxacin, 200 mg orally daily at bedtime, or placebo for the prevention of recurrent bladder infection. Subjects were followed monthly to monitor compliance and symptoms, for urine culture and periurethral and anal canal swabs to monitor colonization, and for blood specimens for hematologic and biochemical studies to monitor safety. During 1 year of follow-up, 10 of 15 placebo subjects and none of 15 norfloxacin subjects developed infection (P less than 0.001). Adverse effects occurred with equal frequencies in the two groups. For norfloxacin subjects, only 2 (1.6%) of 129 periurethral and 4 (3.1%) of 129 anal canal swabs showed colonization with aerobic gram-negative organisms, while 16 (22%) of 73 periurethral and 47 (64%) of 73 anal canal swabs from placebo subjects showed colonization. Daily therapy with norfloxacin at bedtime is effective in preventing recurrent cystitis. During 1 year of norfloxacin therapy, colonization was infrequent and superinfection with norfloxacin-resistant organisms did not occur.

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.

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.

Prospective study of decubitus ulcers in two long term care facilities.

The incidence and prevalence of decubitus ulcers, and their complications and microbiology were studied prospectively in two large long term care facilities in Winnipeg, Manitoba between January 1, 1989 and December 30, 1990. The initial prevalence of decubitus ulcers was 2.6 and 1.6% at the two institutions, with an incidence of 3.4 and 4.8 per 100,000 resident days, respectively. The incidence of decubitus ulcer infection was 1.4 per 1000 ulcer days. The only other complication identified was in one resident who required an indwelling catheter to permit ulcer healing. An average of 2.4 organisms grew from surface swabs of ulcers; anaerobes were isolated from 14% of cultures. Aspirates from clinically noninfected ulcers had bacteria isolated in 30% of specimens. Two-thirds of organisms isolated were considered potentially pathogenic. Concurrent bacteriuria was present for 75% of sampling episodes. Organisms present in the urine were simultaneously isolated from decubiti in only 5% of specimens. Decubitus ulcers are uncommon in long term care institutions. The urinary tract of the bacteriuric elderly appears to be an infrequent source of organisms colonizing decubiti.

Double-blind, randomized comparison of 24 weeks of norfloxacin and 12 weeks of norfloxacin followed by 12 weeks of placebo in the therapy of complicated urinary tract infection.

We evaluated the benefits of prolonging norfloxacin therapy from 12 to 24 weeks for complicated urinary tract infection in a double-blind, randomized, placebo-controlled study. During the second 12 weeks, norfloxacin was superior to placebo (P less than 0.05) in suppressing bacteriuria. Adverse effects were common but mostly confined to the initial 12 weeks.

Emergence of tobramycin-resistant S. epidermidis possessing aminoglycoside modifying enzymes and bacteremic superinfection during empiric therapy of febrile neutropenic episodes.

During a randomized clinical trial comparing tobramycin plus ticarcillin to netilmicin plus ticarcillin as empiric therapy of febrile neutropenic patients, Staphylococcus epidermidis emerged as the predominate superinfecting pathogen in tobramycin recipients. Overall clinical response was 68% (44/65 responding) in tobramycin/ticarcillin recipients and 73% (45/62) in netilmicin/ticarcillin recipients. However, 5/65 tobramycin/ticarcillin treated episodes were complicated by bacteremic superinfection with Staphylococcus epidermidis, as compared to 0/62 netilmicin/ticarcillin treated episodes (p less than 0.05). Four of the five bacteremic strains produced aminoglycoside adenylating enzyme ANT 4', 4''. Prior colonization of patients with identical strains was demonstrated by plasmid profile analysis, antibiograms and biotyping with the API Staph-Ident system. During the trial, 36 consecutive patients were studied for colonization patterns with coagulase-negative staphylococci. S. epidermidis accounted for 566/831 (68%) isolates of coagulase-negative staphylococci recovered from surveillance cultures. Tobramycin-resistant strains were acquired in 2/17, 4/12 and 9/14 patients during trimethoprim/sulfamethoxazole, netilmicin/ticarcillin and tobramycin/ticarcillin therapy, respectively. Prior to aminoglycoside therapy, 77% of strains were susceptible to less than or equal to 8 micrograms/ml of tobramycin, but only 35% and 28% were susceptible to tobramycin after initiation of tobramycin/ticarcillin and netilmicin/ticarcillin therapy, respectively. In contrast, greater than or equal to 93% of isolates were susceptible to netilmicin before and after aminoglycoside therapy. Absence of several sites susceptible to modification by aminoglycoside inactivating enzymes produced by staphylococci may give netilmicin a therapeutic advantage in the therapy of febrile neutropenic patients.