Efficacy of cefepime in the treatment of infections due to multiply resistant Enterobacter species.

Cefepime is a new cephalosporin with an enhanced antibacterial potency and spectrum. More rapid penetration into many gram-negative bacilli, targeting of multiple penicillin-binding proteins, and resistance to inactivation by many beta-lactamases account for its activity against organisms that have developed resistance to agents such as ceftazidime, cefotaxime, or ceftriaxone. This study identified 16 patients with 17 infections due to Enterobacter species organisms with reduced susceptibility or resistance to ceftazidime. Most isolates were multiply resistant to other beta-lactam drugs as well, but all were susceptible to cefepime. All 17 infections, which included pneumonia, urinary tract infection, intraabdominal infection, and bacteremia, responded clinically to intravenous cefepime. In particular, cefepime was successfully used in the management of cases of chronic infection that had responded poorly to repeated therapy with imipenem, aminoglycosides, or ciprofloxacin. Eradication of Enterobacter species organisms occurred at 15 (88.2%) of the 17 sites of infection. No emergence of resistance to cefepime was noted.

Prevalence and characteristics of nursing home-acquired infections in the aged.

OBJECTIVES: This study provides estimates of the prevalence of infections in all patients from a representative sample of 53 Maryland nursing homes; identifies risk factors for these infections; and describes diagnostic procedures carried out. METHODS: The records of 4,259 patients in a stratified random sample of 53 Maryland nursing homes were reviewed for diagnostic procedures, medical, functional, and behavioral status. Infections were identified by signs, symptoms, and laboratory findings. RESULTS: Study patients were characteristic of aged patients in US nursing homes. The prevalence of infections actually acquired in the nursing home (80% of all infections) was 4.4%. Multivariate analysis revealed that skin infections (35% of nursing home-acquired infections) were associated with skin ulcers and inversely with urine incontinence. Fevers of uncertain source (13%) were associated with bladder catheters. Symptomatic urinary infections (12%) and lower respiratory infections (12%) were associated with bedfast status, and the latter with tracheostomy and lung disease. Skin ulcers, urethral catheters, and bedfast status were markers for nursing home-acquired infection. The prevalence of infection in patients with all three markers was 32%; in patients with none, 2%. Fewer than a quarter of the four most common nursing home-acquired infections received an evaluation which met minimal diagnostic criteria established by a panel of infectious disease specialists and geriatricians. Patients with dementia, those in large homes (greater than 150 beds), and those in urban homes were less likely to be evaluated in a manner meeting these criteria. CONCLUSIONS: Use of three characteristics (ie skin ulcers, urethral catheters, bedfast status) to identify patients at risk for nursing home-acquired infections may allow targeted infection surveillance and prevention programs. In addition, nursing home-acquired infections are not evaluated uniformly across patients and facilities, suggesting the need to establish, through further study, guidelines for such evaluations.

The prevalence of urethral catheterization in Maryland nursing homes.

Urinary incontinence is common in the increasing numbers of aged people and is often the precipitating factor for nursing home admission. Recalcitrant incontinence may be managed by urethral catheters. In this study of a random stratified sample of Maryland nursing homes (4259 patients), we found that the daily prevalence of urethral catheter use in Maryland nursing homes was 7.5%. More than 80% of urethral catheter users were women. Among men, we found equal prevalences of urethral and condom catheter use. Previous studies have demonstrated long-term use of urethral catheters to be associated with almost universal bacteriuria of a polymicrobial and dynamic nature. Combining these data suggests that long-term catheter-associated bacteriuria is the most common infection in American health care facilities.

Nosocomial sepsis in the neonatal intensive care unit.

During a 12-month study of the causes of and risk factors for nosocomial sepsis in a neonatal intensive care unit (NICU), we detected 23 episodes of nosocomial sepsis in 20 of the 155 infants at risk who were hospitalized in the NICU for at least one week. The associated mortality was 20%. Gram-positive organisms accounted for 15 (65%) of the episodes. Low birth weight, multiple gestation, and prolonged hospitalization were significant risk factors for nosocomial sepsis by univariate analysis; together, these three factors correctly predicted 80% of the infants with sepsis and 82% of the control subjects. By logistic regression analysis, however, length of stay was not a significant risk factor, but rather a confounding variable that was highly associated with birth weight. Analysis of risk factors for nosocomial sepsis showed that previous antibiotic therapy placed an infant at risk for candidemia; assisted ventilation was a risk factor for sepsis caused by group D Streptococcus and Candida albicans. Sepsis was related to infected or malfunctioning intravascular catheters in nine of the 20 infants with sepsis. Further investigation to determine strategies for preventing nosocomial septicemia in the low birth weight infant is warranted.

Once-daily irrigation of long-term urethral catheters with normal saline. Lack of benefit.

Urinary incontinence is often managed with a long-term urethral catheter after other methods have failed. Such urethral catheterization is associated with polymicrobial bacteriuria, catheter obstruction, fever, bacteremia, urinary tract stones, and death. Periodic catheter irrigation is a common but untested management procedure intended to prevent catheter obstruction, fevers, and/or bacteremia. To evaluate this technique, we performed a randomized crossover trial comparing ten weeks of once-daily normal saline irrigation with ten weeks of no irrigation in 32 long-term catheterized women. The incidence of catheter obstructions and febrile episodes and the prevalence and species of bacteriuria were similar whether examined as completed crossover patients (N = 23) or as partially completed trials (N = 9). Once-daily irrigation with normal saline of long-term urethral catheters is a time-consuming and costly procedure that is unlikely to have an impact on the morbidity associated with such catheters.

Infection control in Maryland nursing homes.

We surveyed 53 randomly chosen Maryland nursing homes for infection control policies and practices. The majority had written infection control policies, an infection control committee, and a designated practitioner for infection control; in most facilities, however, the infection control practitioner had other major duties, spent little time on infection control, and had no specific training in the field. Thirty-four percent of homes in the survey performed routine environmental cultures, and more than half had insufficient or no isolation policies for infected decubiti and acute diarrhea. In general, the intensity of infection surveillance and the extent of infection control measures increased with the level of care provided, from domiciliary homes to homes providing chronic care. Employee health care fared generally well: 60% of homes offered influenza vaccine to employees and 66% had restriction policies for employees with upper respiratory infections. While the majority of homes offered the influenza vaccine to residents, acceptance of other vaccines recommended for the elderly was less widespread. We conclude that infection control efforts are made in most Maryland nursing homes; however, appropriate guidelines and more effort to educate nursing home personnel in proper infection control practices are badly needed.

Obesity and diabetes as risk factors for postoperative wound infections after cardiac surgery.

During a 30-month period, 20 median sternotomy wound infections or endocarditis occurred after 20 of 1204 (1.7%) cardiac surgery procedures in adults at the University of Maryland Hospital. We examined four risk factors related to the individual undergoing surgery: age, sex, and index of obesity (weight/height), and presence of diabetes mellitus. The odds ratio estimates of the relative risk of infection observed with use of a population control group were as follows: sex (female) 3.5 (p less than 0.05), obesity 2.0, and presence of diabetes mellitus 3.8. For a second control group matched for age, type of operative procedure, and date of operation, the estimated relative risks of infection were sex (female) 2.1, obesity 6.2 (p less than 0.05), and diabetes mellitus 2.0. More precise definition of the relative risk of sternotomy infection associated with obesity and diabetes is required to aid surgeons and patients in making judgments about the relative benefits of surgery and to alert nursing personnel to be particularly aware of early signs of infection in patients at high risk.

MR/K hemagglutination of Providencia stuartii correlates with adherence to catheters and with persistence in catheter-associated bacteriuria.

Providencia stuartii was the most prevalent bacterial species isolated, for one year, from weekly urine specimens from 51 long-term catheterized patients. Significantly more strains causing bacteriuric episodes of long duration expressed MR/K (mannose-resistant/Klebsiella-like) hemagglutination (74%) than did those causing episodes of short duration (26%; P = .004). Isolates expressing MR/K hemagglutinin bound in higher numbers to catheter material (P = .023) than did those not expressing this hemagglutinin. Significantly more strains causing bacteriuric episodes of short duration expressed the mannose-sensitive (MS) hemagglutinin (43%) than did those causing episodes of long duration (7%; P = .014). Isolates expressing MS hemagglutinin bound significantly more 125I-labeled Tamm-Horsfall protein (THP) than did isolates not expressing this hemagglutinin (P = .0001). Our results indicate that MR/K hemagglutinin plays an important role in the ability of P. stuartii to persist and suggest that MR/K adheres to the catheter. Conversely, MS hemagglutinin binds to THP and may prevent persistence of P. stuartii in the catheterized urinary tract.

Expression of type 1 fimbriae may be required for persistence of Escherichia coli in the catheterized urinary tract.

Long-term urinary catheterization results in polymicrobial bacteriuria and is complicated by fever, bacteremia, acute pyelonephritis, and death. Escherichia coli is a common urine isolate from catheterized patients and can persist for months. We hypothesized that fimbria-mediated adherence contributes to its persistence. For 1 year, urine specimens were collected from 51 patients greater than or equal to 65 years of age who were catheterized for greater than or equal to 30 days. E. coli was isolated at greater than or equal to 10(5) CFU/ml from 447 (36%) of 1,230 weekly urine specimens from 26 patients. Week 1 isolates from 52 definable episodes were tested for hemagglutination, hybridization with gene sequences from the pil and pap operons, in vitro adherence to catheter material, binding of 125I-labeled Tamm-Horsfall protein, hemolysin and colicin V production, and serum resistance. The proportions of isolates of short (1 week only), medium (2 to 11 weeks) and long (greater than or equal to 12 weeks) episodes of bacteriuria which expressed type 1 fimbriae as assayed by mannose-sensitive hemagglutination were 59, 65, and 92%, respectively. Isolates with the pil operon (the genome for type 1 fimbriae) from episodes lasting greater than 1 week expressed mannose-sensitive hemagglutination more frequently (P = 0.011) than pil-positive isolates from episodes of less than or equal to 1 week. Isolates from episodes of greater than 1 week also bound significantly more Tamm-Horsfall protein than isolates from episodes of less than or equal to 1 week (P = 0.044). Although nearly half of the isolates produced P fimbriae, an important virulence factor for the development of pyelonephritis, no correlation with persistence could be made. Overall, the E. coli isolates expressed traits similar to those of strains that caused cystitis. Type 1 fimbriae appear to be important for the persistence of E. coli in the long-term-catheterized urinary tract.

Long-term catheter-associated bacteriuria: species at low concentration.

Polymicrobial bacteriuria in patients with long-term (greater than or equal to 30 days) indwelling urethral catheters is common and is associated with potentially serious acute and long-term complications. The dynamics of organisms at low concentration (less than 10(5) cfu/mL) in this setting has not been well-characterized; however, in patients with short-term catheters organisms initially present at low concentration (less than 10(5) cfu/mL) usually grow to high concentration (greater than or equal to 10(5) cfu/mL). At the time of catheter replacement for 7 long-term catheterized patients who were not receiving antibiotics, we identified all species at greater than or equal to 10(2) cfu/mL in fresh urine aspirated from the old indwelling catheter and the new sterile replacement catheter and then determined which of these species were present at high concentration two weeks later. A total of thirty-seven species, nineteen at high and eighteen at low concentration were detected in either the old or the new catheters. Eighteen of the nineteen initially detected at high concentration but only one of the eighteen initially detected at low concentration (p less than 0.001) were present at high concentration two weeks later. In patients with long-term indwelling urethral catheters, the number and multiplicity of species causing bacteriuria at low concentration rival that of species at high concentration; however, species at low concentration usually do not grow to high concentration in the presence of other species at high concentration.

Fever, bacteremia, and death as complications of bacteriuria in women with long-term urethral catheters.

Numbers of nursing home beds now exceed hospital beds in the United States and are usually occupied by women. Urinary incontinence is very common and may be managed with long-term urethral catheters. Bacteriuria invariably results, yet its clinical consequences are not well known. We studied 47 catheterized and bacteriuric women for almost 25 patient-years. The incidence of febrile episodes of possible urinary origin was 1.1 episodes/100 patient-days. Because these were diagnoses of exclusion, even this low incidence may be an overestimate. Most of these episodes were of less than or equal to 38.3 C (101.0 F), lasted for less than one day, and resolved without antibiotic therapy. Six deaths, half the total from all causes, occurred during these episodes, an incidence 60 times that during afebrile periods. Deaths and bacteremias were significantly associated with episodes of greater than or equal to 38.8 C (102.0 F). In the individual patient, these risks should be weighed against benefits of patient comfort, family satisfaction, and prevention and management of decubitus ulcers.

A practical method of estimating stature of bedridden female nursing home patients.

Accurate measurement of stature is important for the determination of several nutritional indices as well as body surface area (BSA) for the normalization of creatinine clearances. Direct standing measurement of stature of bedridden elderly nursing home patients is impossible, and stature as recorded in the chart may not be valid. An accurate stature obtained by summing five segmental measurements was compared to the stature recorded in the patient's chart and calculated estimates of stature from measurement of a long bone (humerus, tibia, knee height). Estimation of stature from measurement of knee height was highly correlated (r = 0.93) to the segmental measurement of stature while estimates from other long-bone measurements were less highly correlated (r = 0.71 to 0.81). Recorded chart stature was poorly correlated (r = 0.37). Measurement of knee height provides a simple, quick, and accurate means of estimating stature for bedridden females in nursing homes.

Routine surveillance for infections in nursing homes: experience at two facilities.

Because the feasibility and usefulness of routine surveillance for infections in nursing homes has been questioned, we reviewed the elements of infection surveillance programs developed by two nursing homes using existing personnel. Although infection definitions and data collection methods differed between the two homes, both homes identified urinary and respiratory tract infections as the major endemic problems at their institutions and demonstrated important clusters of gastrointestinal tract and eye infections. Surveillance data were used to identify individual patients who required follow-up by physicians, to justify special infection control measures for clusters of gastrointestinal tract and eye infections, and to provide the basis for in-service education in infection control. Routine surveillance for infections is both feasible and an integral and valuable part of overall infection control programs at two large Maryland nursing homes.

Recruitment of long-term care facilities for research.

We report the successful recruitment of a stratified random sample of nursing homes in the state of Maryland into three research studies funded by the National Institute on Aging. These studies examine the prevalence of infections and urinary tract instrumentation and the incidence of antimicrobial use in nursing home residents. Following selection of a facility, the administrator was telephoned and a meeting at the home was requested. At this meeting, the project was explained in detail using a packet of promotional information which included a project summary, a listing of project staff and their qualifications, and letters of support from influential organizations. A total of 61 eligible facilities were contacted in order to achieve a group of 53 participating homes with approximately 5000 beds. One hundred percent cooperation was achieved from all strata except small (less than or equal to 50 beds) proprietary comprehensive care facilities, and homes with both comprehensive and domiciliary beds. A direct, personal approach, backed by a carefully prepared study information and the support of medical and nursing home organizations resulted in successful recruitment of 53 (87%) of 61 homes sampled.

On antibiotic prophylaxis in cardiac surgery: a risk factor for wound infection.

During a 30-month period, median sternotomy wound infections or endocarditis developed during the first 60 days postoperatively following 20 of 1,204 (1.7%) adult cardiac procedures at the University of Maryland Hospital. Fifty percent of the infected patients received perioperative clindamycin prophylaxis. A retrospective study was conducted in which the odds ratio estimate of the relative risk of sternotomy infection or endocarditis for patients receiving clindamycin prophylaxis compared with patients receiving cefamandole was found to be 17.0 (p less than .001) using population controls and 8.25 (p less than .001) using matched controls. Seventy-five percent of the organisms causing infections, principally Staphylococcus epidermidis, were resistant in vitro to clindamycin. Perioperative clindamycin administration was not fully effective in preventing wound infection following cardiac surgery at our hospital, thus providing indirect evidence for the efficacy of prophylaxis with cephalosporin-containing regimens. Trials of alternative antibiotics to clindamycin for prophylaxis in penicillin-allergic patients undergoing cardiac surgery are indicated.

Adherence to uroepithelial cells of Providencia stuartii isolated from the catheterized urinary tract.

The long-term catheterized urinary tract appears to offer a niche for Providencia stuartii, otherwise an unusual clinical isolate. P. stuartii, the most frequent and persistent isolate from the urine of 51 long-term catheterized patients, was recovered from 761 of 1230 (62%) weekly urine specimens. To test the hypothesis that prevalence of this species may be due to adherence properties of the organism, 20 selected strains from 14 patients at two nursing homes, representing six distinct serotypes and harbouring combinations of nine different plasmid species, were tested for adherence to uroepithelial cells (UEC). Optimal conditions were determined for differentiating strains on the basis of in vitro adherence to UEC. These strains, grown in nutrient broth, were incubated with UEC isolated from the urine of a healthy adult female (10(8) bacteria per 10(5) cells). Washed UEC, retained on 8 micron pore diameter filters, were transferred to slides, fixed and stained; bacteria were counted on each of 40 cells. Fourteen of the 20 strains were defined as adherent to UEC by comparison of mean adherent bacteria and percentage of uroepithelial cells with more than 10 bacteria. Adherence was compared to that of a P-fimbriated strain of Escherichia coli. It was not inhibited by 50 mM-mannose. We conclude that the majority of P. stuartii isolates are adherent to UEC in vitro and suggest that this may play a role in the persistence of this organism in the catheterized urinary tract.

Informed consent by proxy. An issue in research with elderly patients.

The need for clinical study of patients in nursing homes is growing as this population grows; yet many of these patients are mentally incompetent to give informed consent for such research, and the decision must therefore be left to family members or other proxies. We studied the decisions by the proxies for 168 patients in nursing homes about whether to permit the patients' participation in a study involving minimal risk. The proxies were family members in all but one case, and 78 of 168 (46 percent) refused consent. Refusal was significantly associated (P less than 0.001) with the views that research should not be done in nursing homes, that the study would disturb the patient, that the patient, if able, would refuse to participate in the study, and that the proxy would refuse to participate in such a study if asked. Of the 55 proxies who believed that the patient would refuse consent, however, 17 (31 percent) gave consent, in apparent opposition to the patient's wishes. We conclude that refusal by family members to allow incompetent elderly patients to participate in studies may be an important obstacle to research among the elderly. Both the selection of proxies and the bases for their decisions require further study and definition.

Adherent microorganisms on lumenal surfaces of long-term intravenous catheters. Importance of Staphylococcus epidermidis in patients with cancer.

Using electron microscopy, we prospectively evaluated how frequently adherent microorganisms colonized silicone rubber intravenous (Hickman) catheters removed from patients with cancer. Thirteen (87%) of 15 catheters had gram-positive cocci in glycocalyx adherent to the surface of the catheter lumen. Fungal elements or gram-negative bacilli were mixed with the gram-positive cocci in the glycocalyx on the lumens of three catheters. A consistent morphologic form was adherent to, and the same species was recovered from, the corresponding catheter for six of 27 organisms causing septicemia during catheterization: four of five Staphylococcus epidermidis bacteremias and the only Staphylococcus aureus bacteremia, and one of five candidemias. Three of these six septicemias were successfully treated without removal of the catheter. Although adherent organisms, particularly S epidermidis, were likely to be present on the surface of the lumen of long-term, indwelling, silicone intravenous catheters, septicemias potentially related to these organisms occurred infrequently (fewer than two per 1000 days of catheter use), and the suspect septicemias could sometimes be treated without removal of the catheter.

Do clinical microbiology laboratories report complete bacteriology in urine from patients with long-term urinary catheters?

Bacteriuria associated with long-term urinary catheters (those in place for greater than or equal to 30 days) appears to be the most common nosocomial infection in U.S. medical care facilities. This bacteriuria is polymicrobial and dynamic and accompanied by fevers, catheter obstructions, bacteremias, and deaths. We compared the reporting by our research laboratory of bacteria present in urine from long-term-catheterized nursing home patients with that by two commercial laboratories. The commercial laboratories isolated significantly fewer bacterial species at 10(5) CFU/ml of urine specimen. Organisms well recognized as causes of urinary tract infections in noncatheterized patients (Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae) were isolated in comparable frequencies by both the research and commercial laboratories. However, other organisms, including uncommon uropathogens like Providencia stuartii and Morganella morganii, which were actually among the most frequent bacteriuric species in these long-term-catheterized patients, were isolated significantly less frequently by the commercial laboratories. Reasons for the discrepancies are unclear but may involve use of different techniques. More complete reporting may lead to better understanding of the polymicrobial bacteriuria of long-term catheters and its associated complications. This, in turn, may result in improved patient care and infection control in nursing homes.