R. P. Wenzel

Systemic inflammatory response syndrome, sepsis, severe sepsis and septic shock: incidence, morbidities and outcomes in surgical ICU patients

ObjectivesTo determine the incidence of systemic inflammatory response syndrome (SIRS), sepsis and severe sepsis in surgical ICU patients and define patient characteristics associated with their acquisition and outcome.DesignOne-month prospective study of critically ill patients with a 28 day in-hospital follow up.SettingSurgical intensive care unit (SICU) at a tertiary care institution.MethodsAll patients (n=170) admitted to the SICU between April 1 and April 30, 1992 were prospectively followed for 28 days. Daily surveillance was performed by two dedicated, specifically-trained research nurses. Medical and nursing chart reviews were performed, and follow up information at six and twelve months was obtained.ResultsThe in-hospital surveillance represented 2246 patient-days, including 658 ICU patient-days. Overall, 158 patients (93%) had SIRS for an incidence of 542 episodes/1000 patients-days. The incidence of SIRS in the ICU was even higher (840 episodes/1000 patients-days). A total of 83 patients (49%) had sepsis; among them 28 developed severe sepsis. Importantly, 13 patients had severe sepsis after discharge from the ICU. Patient groups were comparable with respect to age, sex ratio, and type of surgery performed. Apach II score on admission to the ICU and ASA score at time of surgery were significantly higher (p<0.05) only for patients who subsequently developed severe sepsis. The crude mortality at 28 days was 8.2% (14/170); it markedly differed among patient groups: 6% for those with SIRS vs. 35% for patients with severe sepsis. Patients with sepsis and severe sepsis had a longer mean length of ICU stay (2.1±0.2 and 7.5±1.5, respectively) than those with SIRS (1.45±0.1) or control patients (1.16±0.1). Total length of hospital stay also markedly differed among groups (35±9 (severe sepsis), 24±2 (sepsis), 11±0.8 (SIRS), and 9±0.1 (controls, respectively).ConclusionsAlmost everyone in the SICU had SIRS. Therefore, because of its poor specificity, SIRS was not helpful predicting severe sepsis and septic shock. Patients who developed sepsis or severe sepsis had higher crude mortality and length of stay than those who did not. Studies designed to identify those who develop complications of SIRS would be very useful.

The significance of nasal carriage of Staphylococcus aureus and the incidence of postoperative wound infection

Staphylococcus aureus infections are associated with considerable morbidity and, in certain situations, mortality. The association between the nasal carriage of S. aureus and subsequent infection has been comprehensively established in a variety of clinical settings, in particular, patients undergoing haemodialysis and continuous ambulatory peritoneal dialysis (CAPD), and in patients undergoing surgery. Postoperative wound infections are associated with a high degree of morbidity and represent an important medical issue. Until recently, eradication of S. aureus nasal carriage by various topical and systemic agents had proved unsuccessful. Mupirocin is a novel topical antibiotic with excellent antibacterial activity against staphylococci. Recent studies have demonstrated that intranasal administration of mupirocin is effective in eradicating the nasal carriage of S. aureus and in reducing the incidence of S. aureus infections in haemodialysis and CAPD patients. It has been suggested that sufficient evidence now exists to test the hypothesis that eradication of the carrier state in surgical patients preoperatively may reduce the incidence of S. aureus postoperative wound infections.

Comparative evaluation of an automated ribotyping system versus pulsed-field gel electrophoresis for epidemiological typing of clinical isolates of Escherichia coli and Pseudomonas aeruginosa from patients with recurrent gram-negative bacteremia☆

Ribotyping and macrorestriction analysis of chromosomal DNA using pulsed-field gel electrophoresis (PFGE) are among the more useful molecular epidemiologic typing methods. Because these techniques are labor intensive, automation of one or more steps may allow clinical laboratories to apply molecular typing methods. We compared the recently developed automated ribotyping system, the RiboPrinter Microbial Characterization System (DuPont), with PFGE as a means of typing clinical isolates of E. coli and P. aeruginosa. A total of 22 E. coli and 24 P. aeruginosa were typed by both PFGE and the RiboPrinter. When compared with PFGE typing of E. coli and P. aeruginosa, the RiboPrinter was less sensitive in identifying different strains, particularly among the isolates of P. aeruginosa. The RiboPrinter was completely automated and allowed up to 32 isolates to be typed within an 8-hour period. The pattern of results obtained in this study suggests that a heirarchical approach to molecular typing using the RiboPrinter Microbial Characterization System plus PFGE might be feasible. The RiboPrinter Microbial Characterization System promises to be a very useful addition to the expanding molecular typing armamentarium.

Association of secondary and polymicrobial nosocomial bloodstream infections with higher mortality

The objective of this study was to characterize microbiological factors independently associated with higher mortality rates following nosocomial bloodstream infection. All patients admitted to the University of Iowa Hospitals and Clinics between 1 July 1989 and 30 June 1990 who developed a nosocomial bloodstream infection were included. The crude in-house mortality for the 364 patients with nosocomial bloodstream infections was 33 %. These deaths accounted for 25 % of all in-hospital deaths. Significant risk factors for death from bloodstream infection included diagnoses of cancers and diseases of the cardiovascular and respiratory systems (p<0.01). Neither previous surgery nor neutropenia was associated with higher mortality rates. Whereas the crude mortality rates associated with gram-negative (33 %) and gram-positive (31 %) bloodstream infections were similar, that associated with fungemia was higher (54 %, p<0.02). The mortality associated with secondary bloodstream infections (46 %) was higher than that associated with primary bloodstream infections (28 %, p<0.001). Furthermore, polymicrobial infections had a worse prognosis than infections from which a single pathogen was isolated (p<0.05). A multivariate, logistic regression model identified four variables that independently predicted mortality (p=0.025): age (OR 1.01 per year; CI95 1.00–1.02); cancer (OR 2.35, CI95 1.26–4.37) or diseases of the cardiovascular or respiratory systems (OR 2.20, CI95 1.04–4.67); polymicrobial infection (OR 2.34; CI95 1.21–4.53); and secondary bloodstream infection (OR 2.46; CI95 1.50–4.02). The last variable was the strongest independent predictor. Our study demonstrates the importance of microbiological factors in the outcome of nosocomial bloodstream infections.

An outbreak of Candida parapsilosis prosthetic valve endocarditis

Candida parapsilosis, an important nosocomial pathogen and the most common species of Candida found on the hands of health care workers, is a rare cause of prosthetic valve endocarditis (PVE). From March through June 1994, four cases of C. parapsilosis PVE were diagnosed at a 400-bed community hospital. The mean time to presentation after valve replacement surgery was 148 days (range, 20 to 345). Three of the four patients died of complications of PVE. Multiple environmental cultures were performed, and only one was positive for C. parapsilosis. Cultures from the bypass pump, cell saver, cardioplegia solution, and subsequent valves were all negative. All valve replacements were performed by the same operating room team. Interviews with the surgeon and physician assistant, the only personnel involved in all cases, revealed that their hypoallergenic gloves were subject to frequent tears during valve replacement procedures, often requiring several glove changes per procedure. Hand cultures of personnel were obtained, and cultures from 20 individuals (26%) were positive for C. parapsilosis. Hand cultures of the surgeon and physician assistant obtained 8 months after the last case had surgery were negative for yeasts. Molecular typing of the 3 available case isolates, 14 epidemiologically unrelated patient isolates, 1 environmental isolate, and 20 hand isolates was performed by electrophoretic karyotyping and restriction endonuclease analysis of genomic DNA using restriction enzymes BssHII and EagI followed by pulsed field gel electrophoresis. The three case isolates were identical by restriction endonuclease analysis of genomic DNA, and two of the three shared the same electrophoretic karyotyping profile. The remaining patient, environmental, and hand isolates represented 29 different DNA types and were distinctly different from the case isolates. All of the isolates tested were susceptible to amphotericin B, 5FC, fluconazole, and itraconazole. The circumstantial evidence suggests the probability of glove tears during valve replacement surgery and subsequent transmission of C. parapsilosis to patients.

The Dynamics of Disease Progression in Sepsis: Markov Modeling Describing the Natural History and the Likely Impact of Effective Antisepsis Agents

We conducted a 9-month prospective cohort study of 2,527 patients with systemic inflammatory response syndrome in three intensive care units and three general wards in a tertiary health care institution. Markov models were developed to predict the probability of movement to and from more severe stages--sepsis, severe sepsis, or septic shock--at 1, 3, and 7 days. For patients with sepsis, severe sepsis, and septic shock, the probabilities of remaining in the same category after 1 day were .65, .68, and .61, respectively. The probability for progression after 1 day was .09 for sepsis to severe sepsis and .026 for severe sepsis to shock. The probability of patients with sepsis, severe sepsis, and septic shock dying after 1 day was .005, .009, and .079, respectively. The model can be used to predict the reduction in end organ dysfunction and mortality with use of increasingly effective antisepsis agents.

An experimental model for study ofCandida survival and transmission in human volunteers

In order to determine the potential for cross-transmission ofCandida spp. between health-care workers and patients, the survival of clinical isolates of five species ofCandida on the palms of human volunteers was tested. One hundred µl of a McFarland 1.0 density suspension (5×105 cfu) from an overnight culture ofCandida albicans, Candida krusei, Candida parapsilosis, Candida tropicalis andCandida glabrata was used as inoculum. The degree of hydrophobicity of the differentCandida species was also tested and did not influence the survival. The half-lives were brief, being 9.5, 12.4, 7.4, 12.8, 9.6 min forCandida albicans, Candida krusei, Candida glabrata, Candida parapsilosis, andCandida tropicalis, respectively, but at 45 min 2.6 × 103 to 3 × 104 organisms remained on the hands. Survival ofCandida albicans for as long as 24 h on inanimate surfaces was observed. Transmission from one hand to a second hand occurred in 69 % of the experiments and from the first to a third hand in 38 %. Transmission to and from inanimate surfaces was successful in most of the experiments (90 %). This experimental model aids in the biological study ofCandida spp. and suggests some of the potential mechanisms of transmission.

The use of biotyping and DNA fingerprinting in typing Canadida albicans from hospitalized patients

The application of typing procedures for the purpose of strain differentiation among isolates of Candida albicans obtained from hospitalized patients has been limited. We have applied biotyping and DNA restriction fragment analysis (DNA fingerprinting) by using EcoRI to the study of C. albicans isolates obtained from hospitalized patients. A total of 68 isolates from 15 patients were studied. Thirteen subtypes were identified by biotyping, 8 by DNA fingerprinting, and 21 by a combination of the biotyping and DNA fingerprinting approaches (composite subtype). Both techniques were highly reproducible. In examining the strain variation among isolates obtained from multiple anatomic sites over time, we found that similar, if not identical, strains were recovered from the oropharynx, urine, stool, and blood in a given patient, and these strains persisted. Only rarely did two patients share the same composite subtype suggesting sporadic nosocomial transmission. The combination of biotyping and DNA fingerprinting improved strain discrimination compared to either method alone. Further investigation with these and other epidemiologic typing methods will be necessary to enhance the understanding of the epidemiology and pathogenesis of candidiasis in hospitalized patients.

A four-year prospective study on microbial ecology of explanted prosthetic hips in 52 patients with “aseptic” prosthetic joint loosening

The bacteriology of explanted prosthetic hips and surrounding soft tissue was studied in 52 patients undergoing surgical revision for joint loosening. In a prospective four-year study, positive bacterial cultures were recorded in 34 (76%) patients. Coagulase-negative staphylococci were the predominant isolates, and 11 patients (33%) had more than three organisms isolated, 7 (20%) had two only, and 11 (33%) had one species. Among the 23 patients from whom specimens from all 11 predetermined anatomic sites were cultured, the highest frequency of positive cultures (52% and 47%) came from the shaft and capsular tissue, respectively. Organisms were less frequently recovered from the cement and acetabulum (13% and 4%, respectively). Using molecular typing in eight patients with paired isolates of the same species, clonal identity was found in four. An additional patient underwent a second revision for loosening 17 months after the first revision and the same clone ofStaphylococcus epidermidis was isolated on both occasions.

Value of the Cand-Tec Candida antigen assay in the diagnosis and therapy of systemic candidiasis in high-risk patients

A total of 911 sera from 171 patients at risk for systemic candidiasis and 24 sera from 24 non-hospitalized control subjects were analyzed for the presence of candida antigen using a commercially available latex agglutination test (Cand-Tec). Thirty-seven (22 %) patients had systemic candidasis documented by positive blood cultures, deep biopsy culture and histopathology or autopsy. Six patients had transient candidemia, 20 patients had candiduria, 53 patients had mucous membrane colonization, 21 patients were not colonized but received empiric amphotericin B, and 34 patients were not colonized and not treated with amphotericin B. The intraobserver reproducibility was 90 % for the exact titer and 100 % for a deviation of one dilution. The sensitivity and specificity of the candida antigen test in detection of systemic candidasis was 95 % and 50 % (≥ 1: 2), 73 % and 72 % (≥ 1 : 4), and 46 % and 80 % (≥ 1 : 8) respectively. Despite the poor specificity, serial antigen determinations in patients with documented systemic candidiasis demonstrated both an early diagnostic and prognostic role for the candida antigen test. Seventy-one percent of patients whose antigen titer increased during the course of amphotericin B therapy of documented infection died versus only 13 % of those whose titer decreased while on therapy (p = 0.01). The candida antigen test has a limited yet potentially useful role in the diagnosis and management of systemic candidasis in high-risk patients.