Epidemiology, treatment and outcome of candidemia: a five-year review at three Canadian hospitals.

To determine treatment regimens and epidemiological patterns in the occurrence of candidemia, a review of cases occurring from 1992 to 1996 in three large Canadian hospitals, University of Alberta Hospital (UAH) and Royal Alexandra Hospital (RAH), Edmonton, and Foothills Medical Center (FMC), Calgary, was carried out. Cases were detected by reviewing microbiology laboratory records. There were 202 cases in all (UAH 104, FMC 70, RAH 28). For the five study years the candidemia rate was 4.5/10 000 discharges (UAH 7.6, FMC 4.9, and RAH 1.7; P < 0.05 for all interhospital comparisons). The rate remained stable between 1992 and 1995 but rose dramatically in 1996 to 7.6/10 000 (P < 0.01 compared to 1995) as a result of increases at UAH and RAH. Of the 208 species identified, Candida albicans accounted for 135 (65%). During hospitalization 93 (46%) patients died. Species did not influence outcome. Antifungal treatment with fluconazole alone was given to 14% of patients, and increased in frequency throughout the study. No antifungal therapy was given to 47 patients (23%). This group had a much higher mortality (68%) than those who received treatment (39% P < 0.01). Twenty of the untreated patients had already died by the time the blood culture had been reported as growing a yeast. Candidemia rates vary significantly between hospitals and increased in some but not all over the five study years. As many patients with candidemia will have died by the time laboratory diagnosis is made, presumptive antifungal therapy in high-risk patients may be necessary if outcome is to be improved.

M(2) and M(4) muscarinic receptor subtypes couple to activation of endothelial nitric oxide synthase.

In this report we studied coupling of M(2) and M(4) muscarinic acetylcholine receptors to activation of endothelial nitric oxide synthase (eNOS). Chinese hamster ovary cells that co-express the individual receptor subtypes and eNOS in a stable fashion were used as a model. Activation of eNOS was assayed by measuring increasing levels of cyclic GMP in admixed cells that contain guanylate cyclase. Activation of both M(2) or M(4) muscarinic receptors resulted in marked activation of eNOS, in a time- and concentration-dependent manner. The time course of the response exhibited a transient peak, followed by a sustained lower plateau. While the sustained phase was dependent on influx of extracellular calcium, the transient response showed dependency on both mobilization of intracellular calcium and extracellular influx.

Neurokinin(3) receptors couple to the activation of neuronal nitric-oxide synthase in stably transfected Chinese hamster ovary cells.

Several physiological effects induced by activation of neurokinin(3) (NK(3)) receptors are mediated by the production of nitric oxide (NO). We investigated the intracellular coupling of NK(3) receptors to NO synthase (NOS) using a Chinese hamster ovary cell line that was stably transfected with both the NK(3) receptor and type I (neuronal) NOS. NOS activity in the transfected cell line was assayed directly, by measuring the formation of L-citrulline, another product of NOS, as well as indirectly, by measuring the production of cGMP in cultured rat fetal lung fibroblasts (RFL-6 cells). MePhe(7)-neurokinin B (NKB) stimulation of L-[(3)H]citrulline production was concentration-dependent and yielded a two-site model for the concentration-response relationship. The production of L-citrulline in response to two other tachykinins, substance P or neurokinin A, revealed only a one-site nature of the response. The production of cGMP in response to MePhe(7)-NKB had an EC(50) value that corresponded to the high-potency component of MePhe(7)-NKB-induced production of L-[(3)H]citrulline. Agonist-induced calcium signaling was also concentration-dependent, and the acute increase in the production of cGMP by MePhe(7)-NKB (0.1 nM) was dependent on the release of calcium from intracellular stores. Results of this study provide the first direct evidence that NK(3) receptors couple to the generation of NO within the same cell.

Long term trends in the occurrence of nosocomial blood stream infection.

OBJECTIVE: To determine trends in the occurrence of nosocomial blood stream infection at the University of Alberta Hospital. METHODS: A prospective survey of nosocomial blood stream infection was conducted; cases from August 1986 to December 1996 were reviewed. Cases were detected by a review of positive blood cultures reported by the microbiology laboratory. Centers for Disease Control and Prevention definitions of nosocomial infection were used to categorize isolates as nosocomial, community acquired or contaminant. RESULTS: There were 2389 cases; primary bacteremia was the most common source (57%), followed by urinary tract, respiratory tract and surgical site sources (10% each). The nosocomial blood steam infection rate rose progressively from 6.0/1000 admissions and 4.59/10,000 patient days in 1986 to 11.2/1000 admissions and 14.31/10,000 days in 1996 (P<0.01); 48% of the total increase in rate occurred between 1995 and 1996. Significant increases occurred between 1986 and 1996 in primary infections (from 3.2 to 7.5/1000 admissions, P<0.01) and infections from all secondary sources (from 2.5 to 3.8/1000 admissions, P=0.01). Coagulase-negative staphylococci (27%), Staphylococcus aureus (19%) and enterococci (9%) were the most common microbial causes. Aerobic Gram-negative bacilli accounted for 28% and candida for 6%. Coagulase-negative staphylococci, enterococci and candida all became more prevalent as causes of infection over the study period. CONCLUSIONS: The nosocomial blood stream infection rate in the hospital has nearly doubled in the past 10 years, largely due to increased primary bacteremia.

The impact of health care restructuring on nosocomially acquired blood stream infections.

OBJECTIVE: To assess the impact of the health care restructuring, which occurred in Alberta in 1995, on the occurrence of nosocomial blood stream infection and risk factors for these infections at the University of Alberta Hospital. PATIENTS AND METHODS: Changes in patient population, hospital bed numbers, admissions and hospital days for 1993 and 1994 (1993/94) were compared with those for 1996 and 1997(1996/97). Central venous catheter (CVC) use in intensive care units (ICU), days of total parenteral nutrition (TPN) and hemodialysis were compared for the two time periods. Prospectively collected data obtained by monitoring blood culture results on nosocomial blood stream infections in 1993/94 were compared with those obtained in 1996/97. RESULTS: Hospital bed number fell by 10% between 1993/94 and 1996/97. Annual admissions fell by 19% and patient days by 17%. Some services markedly increased patient days (neurosurgery 49%, nephrology 30%, orthopedic surgery 24%), and others markedly reduced patient days (obstetrics and gynecology 99%, ophthalmology 100%, adult medicine 41%, general paediatrics 38%). ICU use of CVCs increased by 41%, TPN days increased by 25% and hemodialysis runs increased by 9%. Annual nosocomial blood stream infections increased by 31% and the annual rate per 10,000 patient days increased by 60%. TPN-related blood stream infection rates and ICU CVC infection rates did not change from 1993/94 to 1996/97. CONCLUSIONS: Hospital restructuring has been associated with a 31% increase in nosocomial blood stream infection number and a 60% increase in rate. The increase has been associated with a change in patient populations and increases in risk factors for blood stream infection.

Peritonitis due to Stenotrophomonas maltophilia in patients undergoing chronic peritoneal dialysis.

The occurrence of cases of Stenotrophomonas maltophilia peritonitis in chronic peritoneal dialysis (PD) patients prompted a review of our experience with this condition. A search of microbiology records revealed seven episodes of S. maltophilia peritonitis in 7 patients in 1996 - 3.8% of all PD patients - compared to no cases in 1994 and 1995 (p = 0.01). Patients ranged in age from 16 to 64 years; there were 3 males and 4 females. Six of seven episodes of peritonitis were community acquired and one was hospital acquired. No temporal clustering of cases was seen. Patients were from different urban and rural communities. Patients used the same commercially supplied dialysate fluid, different dialysis techniques, and were taught a no-touch technique for connection. Treatment of peritonitis required removal of the Tenckhoff catheter in 4 of 7 cases. Fingerprinting of six available isolates by polymerase chain reaction using primers derived from the conserved region of the 16/23Sr RNA gene sequence and pulsed field gel electrophoresis revealed all to be unique strains. A case-control study comparing 7 S. maltophilia cases to 21 PD controls showed case patients to be younger and more likely to be on immunosuppressive therapy. We conclude that S. maltophilia has emerged as an important cause of peritonitis in our continuous ambulatory PD population. Evidence to date suggests community acquisition with no evidence of a common source.

Central venous catheters as a source of hemodialysis-related bacteremia.

OBJECTIVE: To describe investigations into an increase in hemodialysis-related bacteremia that occurred in our hospital in the first 6 months of 1996. SETTING: Hemodialysis unit in a tertiary-care medical center. METHODS: Prospective surveillance for hemodialysis bacteremia has been performed for several years. Cases that occurred in 1995 were compared to cases in the first 6 months of 1996. Unit data on dialysis runs and method of dialysis access were used to calculate rates. Nested polymerase chain reaction (PCR) was used to type 18 Staphylococcus aureus isolates from 1996. A case-control study comparing 80 randomly selected hemodialysis patients from 1995 and 1996 was performed to examine infection risk factors. RESULTS: The hemodialysis bacteremia rate was 1.2 per 1,000 runs in 1995 and 2.8 per 1,000 in the first 6 months of 1996 (P=.0009). The 25 cases in 1995 and 32 in the first half of 1996 were similar in age, gender, means of vascular access, and microbial etiology. Central venous catheter (CVC) access accounted for >90% of cases in both time periods. S aureus was the most common microbial etiology (53% of the 1996 cases). PCR typing of S aureus isolates from 1996 demonstrated five different strains, the most common having six isolates. The use of CVCs as a means of vascular access abruptly increased in the unit in January 1996, from <30% of dialysis runs in 1995 to >40% in 1996 (P<.001), associated with structural changes in healthcare delivery in the region resulting in delays in performing surgical procedures, such as creation of vascular grafts and fistulae. CONCLUSION: A marked increase in hemodialysis bacteremia occurred in 1996, associated with increased reliance on CVCs for vascular access in hemodialysis patients during a period of healthcare restructuring.

Psychological preparation for nasogastric feeding in children.

Psychological preparation of children undergoing enteral nutrition by nasogastric tube was evaluated in a prospective study of 48 children nursed at home. They were randomly allocated to receive either standard informal preparation or detailed psychological preparation and support. The children were divided into two groups according to age: group A comprised toddlers and younger children aged 2-6 years and group B comprised older children and adolescents aged 7-16 years. Detailed questionnaires were administered to all parents and older children by dietetic colleagues who were blinded to the type of preparation received by the children. The results emphasize that detailed psychological preparation of families takes time. Passage of a nasogastric tube was seen as very distressing to both parents and children. Having a nasogastric tube was perceived as a major problem by group A. There was no statistical difference in the effects of enteral nutrition between younger children who received routine preparation and those who received detailed preparation; however, parental assessment of their child's behaviour was the sole means of determining how the younger child felt and reacted. In group B, there were marked differences: scores suggested that those who received detailed preparation had been better prepared for enteral feeding in hospital and at home and that the passage of the nasogastric tube, although unpleasant, was less distressing to them (P < 0.05). Talking to a nurse and play therapist was seen by parents as essential (P < 0.05). The authors conclude that children should be prepared for painful procedures and followed up sensitively, according to their needs.

Bacteremic nosocomial pneumonia. A 7-year experience in one institution.

STUDY OBJECT: To describe the epidemiology, microbiology, and outcome of nosocomial pneumonia with secondary bloodstream infection. DESIGN: Prospective cohort study. SETTING: Tertiary care Canadian teaching hospital. PATIENTS: Inpatients. MEASUREMENT: All inpatient blood cultures were concurrently monitored over an 89 month period. Following chart review, patients experiencing nosocomial bloodstream infection due to pneumonia were identified. A standardized definition of pneumonia was used. RESULTS: One hundred forty-nine episodes occurred in 145 patients, 0.66/1,000 hospital admissions, 8.4% of all nosocomial bloodstream infections. No change in rate occurred in the study period. Fifty-four percent of episodes developed in one of seven ICUs. Staphylococcus aureus was the most frequently identified etiologic organism (27%). The ICU and non-ICU cases did not differ in etiology. No organism became more prevalent during the study period. Twenty percent of patients died within 1 week of first positive culture; episodes associated with Pseudomonas species had a much higher mortality rate (45%) than other infections (14%) (p = 0.002). The ICU and non-ICU infections had a similar mortality rate. CONCLUSION: Pneumonia is an important cause of nosocomial bloodstream infection, but it is not increasing in frequency or changing in etiology in our institution. The ICUs are a major contributor to this problem but have the same case short-term mortality rate and microbial etiology as non-ICU cases. Cases associated with Pseudomonas have a much higher mortality rate.

Trends and sources of nosocomial fungaemia.

Concurrent surveillance of blood culture isolates in a 1000-bed tertiary care hospital over a 7-year period from 1986 to 1993 identified 102 episodes of nosocomial fungaemia, representing 6.6% of all episodes of nosocomial bloodstream infections and 0.49/1000 admissions. No significant change in the frequency, rate, source or microbial aetiology of nosocomial fungaemia occurred over the 7-year period. Candida albicans accounted for 74%, followed by Candida (Torulopsis) glabrata (8%), C. parapsilosis (7%), C. tropicalis (3%), C. lusitaniae (2%), C. krusei, Malassezia furfur Saccharomyces cerevisiae, Hansenula anomala and Cryptococcus albidus (one each). 'Primary' fungaemia, usually attributed to intravascular catheters, was considered to be the source in 65% of cases, with 64% of these patients receiving total parenteral nutrition (TPN). Other important sources of infection included the urinary tract (11%), the gastrointestinal tract (8%) and the respiratory tract (7%). Sixty-four % of patients were in one of the hospital's seven intensive care units (ICUs) when their infection developed, the neonatal ICU and adult medical/surgical ICU each accounting for 21%. Only 7% of cases were associated with neutropenia and another 14% with malignancy or immunosuppression. Death occurred within 7 days of diagnosis of fungaemia in 23 cases. In eight instances, fungaemia was considered the main cause of death. We conclude that in our hospital nosocomial fungaemia is largely caused by C. albicans, occurring in association with intravascular catheter use and TPN in ICU patients. Most cases are not associated with recognized immune defence defects. Fungaemia is associated with a high short-term mortality rate.

Reduction in surgical wound infection rates associated with reporting data to surgeons.

Several studies have shown that wound infection (surgical site infection [ ssi ]) rates fall when surgeons are provided with data on their performance. Since 1987, the authors have been performing concurrent surveillance of surgical patients and confidentially reporting surgeon-specific ssi rates to individual surgeons and their clinical directors, and providing surgeons with the mean rates of their peers. The program has been gradually refined and expanded. Data are now collected on wound infection risk and report risk adjusted rates compared with the mean for hospitals in the United States National Nosocomial Infections Surveillance (nnis) data bank. Since inception through to December 1993, ssi rates have fallen 68% in clean contaminated general surgery cases (relative risk [rr] 0.36, 95% ci 0.2 to 0.6, P=0.0001), 64% in clean plastic surgery cases (rr 0.35, 95% ci 0.06 to 1.8), 72% in caesarean section cases (rr 0.23, 95% ci 0.03 to 1.96) and 42% in clean cardiovascular surgery cases (rr 0.59, 95% ci 0.34 to 1.0). In clean orthopedic surgery the ssi rate remained stable from 1987 through 1992. In 1993 a marked increase was experienced. Reasons for this are being explored. Overall there was a 32% decrease in ssi rate between the index year and 1993 or, in percentage terms, 2.8% to 1.9% (rr 0.65, 95% ci 0.51 to 0.86, P=0.002). ssi surveillance should become standard in Canadian hospitals interested in improving the quality of surgical care and reducing the clinical impact and cost associated with nosocomial infection.

Use of generic quality improvement chart review to recognize nosocomial infection.

BACKGROUND: Generic medical quality improvement concurrent chart review for adverse patient occurrences was introduced into our hospital. To determine whether this program could be used to augment the surveillance activities of the infection control program, an evaluation of this review was carried out and it was compared with existing surveillance methods. METHODS: Analysts were provided with Centers for Disease Control definitions of site infections and were trained in identification. During a 6-month period (period 1) infections in this manner documented were reviewed by infection control program to confirm nosocomial infection as a measure of specificity. Data were also compared with infection control surveillance data when the two programs overlapped (nosocomial bloodstream infections and surgical wound infections) as a check on the sensitivity of the data generated in the medical quality improvement process. A second 6-month review of data (period 2), starting 3 months after completion of period 1, was carried out; this review was limited to areas of overlap and designed to determine whether changes in data occurred with experience. RESULTS: In period 1, 72% (109/152) of infections detected by chart review were confirmed by infection control methods, and 51% (26/51) of infections detected by the infection control program were also detected by chart review. During period 2 the values were 73% (52/71) for confirmed infections and 61% (43/70) for detected infections. There was no statistical difference between periods 1 and 2. In the two periods 25 bacteremic infections went undetected by chart surveyors. CONCLUSION: We conclude that this chart surveillance has only moderate sensitivity and specificity compared with our infection control surveillance methods. Improvements were not demonstrated with experience.