Cryptosporidium enteritis in solid organ transplant recipients: multicenter retrospective evaluation of 10 cases reveals an association with elevated tacrolimus concentrations.

BACKGROUND: Cryptosporidial enteritis, a diarrheal infection of the small intestine caused by the apicomplexan protozoa Cryptosporidium, is infrequently recognized in transplant recipients from developed countries. METHODS: A retrospective review of all cases of cryptosporidiosis in solid organ transplant (SOT) recipients at 2 centers from January 2001 to October 2010 was performed and compared with transplant recipients with community-onset Clostridium difficile infection (CDI). A literature search was performed with regard to reported cases of cryptosporidiosis in SOT recipients. RESULTS: Eight renal, 1 liver, and 1 lung transplant recipient were diagnosed with cryptosporidiosis at median 46.0 months (interquartile range [IQR] 25.2-62.8) following SOT. Symptoms existed for a median 14 days (IQR 10.5-14.8) before diagnosis. For the 9 patients receiving tacrolimus (TAC), mean TAC levels increased from 6.3 ± 1.1 to 21.3 ± 9.2 ng/mL (P = 0.0007) and median serum creatinine increased temporarily from 1.3 (IQR 1.1-1.7) to 2.4 (IQR 2.0-4.6) mg/dL (P = 0.008). By comparison, 8 SOT recipients (6 kidney, 2 liver) hospitalized with community-onset CDI had a mean TAC level of 10.8 ± 2.8 ng/dL during disease compared with 9.2 ± 2.3 ng/mL at baseline (P = 0.07) and had no change in median creatinine. All patients recovered from Cryptosporidium enteritis after receiving various chemotherapeutic regimens. CONCLUSIONS: Cryptosporidiosis should be recognized as an important cause of diarrhea after SOT and is associated with elevated TAC levels and acute kidney injury. Increased TAC levels may reflect altered drug metabolism in the small intestine.

Incidence of Early and Late-Onset Clostridioides difficile Infection following Appendectomy Compared to Other Common Abdominal Surgical Procedures.

Introduction: Clostridioides difficile associated diarrhea (CDAD) is a major public health issue. The appendix may function as a reservoir for the intestinal microbiome, which may repopulate the intestine following enteric infections including CDAD. Patients/Methods. This retrospective cohort study includes a total of 12,039 patients undergoing appendectomy, hemicolectomy, and cholecystectomy at a single center between 1992 and 2011 who were diagnosed with early and late-onset CDAD and were followed for a minimum of two years. Results: Cumulative CDAD rates were 2.3% after appendectomy, 6.4% after left and 6.8% after right hemicolectomy, and 4% after cholecystectomy with a median onset of 76 (range 1-6011) days after the procedure. Median time to CDAD onset was 76 days after appendectomy, 23 days after left, 54 days after right hemicolectomy, and 122 days after cholecystectomy (p < 0.05). Late-onset CDAD (>1 year) was significantly more common following appendectomy (37%) and cholecystectomy (39%) than after left (17%) and right (21%) hemicolectomy. Significant differences in age, gender, complication rate, and length of hospitalization between the four groups need to be considered when interpreting the results. Conclusion: The incidence of CDAD after various abdominal surgeries ranged between 2% and 7% in this study. Whereas, hemicolectomy patients had predominantly early onset CDAD, and appendectomy and cholecystectomy may increase the risk for late-onset CDAD. Appendectomy per se does not seem to increase the risk for late-onset CDAD.

Fatal cross infection by carbapenem-resistant Klebsiella in two liver transplant recipients.

Members of the family Enterobacteriaceae including Klebsiella have re-emerged as major pathogens in solid organ transplantation. The recent appearance and dissemination of carbapenemase-producing Enterobacteriaceae in Europe and the northeastern United States represents a major challenge to the treatment of enteric gram-negative bacterial infections in immunocompromised patients; however, few reports have detailed the outcomes of such infections. Here we report 2 cases of Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella infections in orthotopic liver transplant recipients, which were the index case and initial secondary case for an outbreak of KPC-producing Enterobacteriaceae in our institution. In both instances, the pathogens were initially misidentified as being carbapenem sensitive, the infections recurred after cessation of directed therapy, and the patients ultimately succumbed to their infections.

Pneumonia in solid organ recipients: spectrum of pathogens in 217 episodes.

BACKGROUND: Lower respiratory tract infection (LRTI) remains a leading cause of morbidity and mortality after solid organ transplantation (SOT). PATIENTS AND METHODS: We performed a retrospective analysis of 217 episodes of LRTI in 143 SOT patients from a single center. RESULTS: There were 94 men and 49 women (85% Caucasian) of median age of 51 (range 17-79) years, including 50 renal, 86 liver, 6 pancreas, and 1 lung recipient. Forty patients experienced multiple episodes of LRTI. Median APACHE II score was 17 (range 5-40), median temperature was 38 degrees C (range 35.3 degrees C-40.2 degrees C), and median white blood cell count was 12000 (range 100-106,000). Pneumonia developed at a median of 11 (range 2-191) days after the last surgical intervention. Of the 217 LRTIs, 163 were nosocomial infections (60 ventilator-associated). Overall crude mortality of 21% was increased in patients with multiple episodes of LRTI (25%) and after liver transplantation (33%). In 40 cases, treatment was initiated without identification of a specific pathogen. Overall, 202 microorganisms were found (41 mixed infections): Staphylococcus aureus (n = 32) of which 81% were MRSA; Escherichia coli (n = 9); Klebsiella spp (n = 7); Enterobacter spp (n = 11); Serratia spp (n = 12); Pseudomonas aeruginosa (n = 15); Stenotrophomonas maltophila (n = 15); Acinetobacter spp (n = 9); fungi (n = 18), and viruses (n = 17). CONCLUSION: LRTI remains one of the most common, dangerous infections in transplant recipients with higher mortality than in other populations. MRSA is a particular problem. As a significant number of SOT patients develop multiple episodes of LRTI, a thorough reevaluation of the current guidelines for the treatment of pneumonia is urgently needed.

Laparoscopic gastric banding in a kidney-pancreas transplant recipient with new onset type II diabetes mellitus associated with morbid obesity.

Combined kidney-pancreas transplantation is the treatment of choice for end-stage diabetic nephropathy. Post-transplant weight gain increases the risk for post-transplant complications and death owing to cardiovascular events. Gastric banding is an established treatment for moderate morbid obesity. We report on a patient who experienced significant weight gain and developed type II diabetes mellitus following successful kidney-pancreas transplantation. He underwent laparoscopic gastric banding and initially had good weight loss. However, lack of compliance with dietary guidelines led to transient failure of weight loss therapy. With further adjustment of the gastric band good weight loss was achieved.

Benign transient hyperphosphatasemia associated with Epstein-Barr virus enteritis in a pediatric liver transplant patient: a case report.

Transient hyperphosphatasemia was found in a 3-year-old male liver transplant recipient. The condition was associated with diarrheal disease due to the Epstein-Barr virus (EBV). Immunosuppression was tapered and valganciclovir prescribed for 3 months, after which the diarrhea resolved and the EBV polymerase chain reaction assays became negative. After 6 months, alkaline phosphatase levels normalized. Isolated elevation of alkaline phosphatase in conjunction with enteric infection is a rare condition. No further diagnostic or therapeutic interventions except treatment of the underlying infection are needed, as this has been shown to be a benign, transient condition.

Morning report: combining education with patient handover.

INTRODUCTION: The advent of resident work hour restrictions has challenged us to train residents within a shorter working week, while ensuring continuity of patient care. We instituted morning report (MR) at the University of Virginia primarily as a means to accomplish these objectives. Serendipitously MR has become an integral educational tool for the surgical residents. The rationale for the format and instructional design are discussed in the context of learning theory. METHODS: The chief residents as primary stakeholders were strongly encouraged to play a leadership role in designing MR. A faculty- led didactic format was rejected because of the importance of focusing on resident team building, and leadership, but poor faculty participation was also an issue. RESULTS: The initial obstacles included timing, and designing the format. CONCLUSIONS: MR is an opportunity for residents to exercise and improve their knowledge, leadership, presentation and problem-solving skills. We would hypothesise that the advantages for teaching are many and include that residents are prepared for actual clinical problems in a supportive environment with opportunities for immediate feedback and assessment. Reports of educational effectiveness of MR are mostly anecdotal and further studies are needed to characterise the types of learning and teaching that occur during MR and to document educational effectiveness.

Erratum to: Antimicrobials: a global alliance for optimizing their rational use in intra-abdominal infections (AGORA).

[This corrects the article DOI: 10.1186/s13017-016-0089-y.].

Implant-associated infections: an overview.

The discovery of a 5500-year-old dental implant near Gebel Ramlah, Egypt, marks the earliest discovery of a medical prosthesis. It would not be until the 20th century, however, that this ancient concept would resurface on a wide scale basis. With the introduction of physiologically inert biomaterials in the 1950s, the field of surgical implants has emerged as arguably one of the greatest medical advancements of our time. It is now estimated that millions of patients worldwide have received some type of prosthesis. This forces us to appreciate the impact of implant-associated infections on patients today and mandates that we as a medical community be prepared to manage these infections effectively. This article provides an in-depth review of the current most commonly used prosthetic devices and the infections that accompany them. We examine the epidemiology, diagnosis, prevention, and treatment of various implant-associated infections within the fields of general, plastic, orthopedic, dental, and neurosurgery. We will highlight the recent technological advancements and future prospects. We will also draw attention to the need for further research in this ever growing field.

Incidence and management of biliary complications after 291 liver transplants following the introduction of transcystic stenting.

BACKGROUND: Biliary complications occur frequently after liver transplantation, and many are historically related to T tubes. Stents placed through the donor cystic duct have been used to attempt to reduce tube-related complications yet maintain access to the biliary tree. METHODS: The outcomes of all liver transplant procedures performed at the University of Michigan between December 7, 1990 (when transcystic stenting was first used), and April 6, 1995, were analyzed retrospectively. Preoperative, perioperative, and postoperative variables were studied in relationship to biliary complications. The management of complications was also reviewed. RESULTS: A total of 291 transplants qualified for study. The overall biliary complication rate was 25%, with no difference between the 237 patients who received transcystic stents, the 28 who received T tubes, and the 26 who received no tube. Among the complications patients experienced, 65% had stricture(s), 44% had stone or sludge formation, and 40% had a leak. Complications attributable solely to transcystic stents occurred in 4% of cases. Advanced age was the only preoperative variable associated with complications. Primary sclerosing cholangitis was associated with intrahepatic strictures, and prolonged cold ischemia time and rejection were associated with stone or sludge formation. Nonoperative management had the highest success rate for anastomotic stricture (76%) and the lowest for intrahepatic strictures (65%). Only one death was directly attributable to a biliary complication. CONCLUSION: Transcystic stenting reduces the incidence of significant tube-related complications, but not the frequency of other biliary complications. Biliary complications can usually be managed percutaneously or endoscopically, although intrahepatic strictures and large, early leaks frequently require reoperation. Aggressive, early management of these complications can reduce excess mortality to less than 2%.

Uni- and multi-variate analysis of risk factors for early and late hepatic artery thrombosis after liver transplantation.

BACKGROUND: Hepatic artery thrombosis (HAT) is a significant cause of morbidity after liver transplantation. The aims of this study are to identify and compare risk factors that might contribute to HAT. METHODS: A total of 424 liver transplants performed at the University of Virginia were reviewed. HAT was defined as complete disruption of arterial blood flow to the allograft and was identified in 29 cases (6.8%). HAT was classified as early (less than 1 month posttransplant, 9 cases: 2.1%) or late (more than 1 month posttransplant, 20 cases: 5.4%). Possible risk factors for HAT were analyzed using Pearson chi2 test for univariate analysis and logistic regression for multivariate analysis. RESULTS: Multiple transplants, recipient/donor weight ratio >1.25, biopsy-proven rejection within 1 week of transplant, recipient negative cytomegalovirus (CMV) status, arterial anastomosis to an old conduit (defined as a previously constructed aorto-hepatic artery remnant using donor iliac artery), and CMV negative patients receiving allograft from CMV positive donors were found to be significant risk factors for developing early HAT. After logistic regression, factors independently predicting early HAT included arterial anastomosis to an old conduit [odds ratio (OR)=7.33], recipient/donor weight ratio >1.25 (OR=5.65), biopsy-proven rejection within 1 week posttransplant (OR=2.81), and donor positive and recipient negative CMV status (OR=2.66). Female donor, the combination of female donor and male recipient, recipient hepatitis C-related liver disease, donor negative CMV status, and the combination of recipient CMV negative and donor CMV negative were found to be significant risk factors for late HAT. Factors independently predicting late HAT by logistic regression included negative recipient and donor CMV status (OR=2.26) and the combination of a female donor and male recipient (OR=1.97). CONCLUSION: Therefore, in nonemergency situations attention to these factors in donor allocation may minimize the possibility of HAT.

Cellular mechanisms of abscess formation: macrophage procoagulant activity and major histocompatibility complex recognition.

BACKGROUND: Macrophage procoagulant activity (PCA) has been proposed as a key mediator of abscess formation. Experimentally, transient systemic bacterial infection lead to increased numbers of intraabdominal abscesses after a subsequent episode of peritonitis. We tested the hypothesis that these events were regulated by classic major histocompatibility complex (MHC)-restricted antigen processing and presentation to lymphocytes followed by lymphocyte-mediated up-regulation of macrophage PCA. METHODS: In vitro, macrophages and lymphocytes from BALB/c or C57BL/6 mice either untreated or preexposed to Escherichia coli were coincubated with bacteria or lipopolysaccharide. Cell lysates were tested for PCA in a one-step dotting assay. In vivo, mice were either preexposed to E. coli or received passive transfer of lymphocytes from MHC-compatible or MHC-incompatible and naive or preexposed donors; peritonitis and intraabdominal abscesses were afterwards induced with E. coli, Bacteroides fragilis, and a sterile fecal adjuvant. Mice were killed after 10 days and were studied for abscess number and bacterial composition. RESULTS: The presence of lymphocytes consistently increased macrophage PCA; lymphocytes from preexposed donors induced twice as much PCA as lymphocytes from naive donors regardless of MHC background. Both bacterial preexposure and passive transfer of lymphocytes from preexposed donors increased later intraabdominal abscess number in an MHC-restricted fashion. CONCLUSIONS: Transient infections enhance subsequent lymphocyte-mediated macrophage PCA, correlating with increases in abscess formation after peritonitis. The need for MHC identity to reproduce these results via passive transfer in vivo is consistent with classic T-cell receptor-mediated antigen presentation and lymphocyte activation before enhancement of PCA during peritonitis.

Bacterially preexposed T cells impair bacterial elimination by non-Th1/Th2 cell mechanisms in a model of intra-abdominal infection.

BACKGROUND: Escherichia coli preexposure in mice results in impaired elimination of subsequent intra-abdominal infections by a CD+4 T cell-dependent process. Certain gram-negative infections have been shown to induce T-helper-(Th)2 type CD4+ T-cell differentiation, which correlates with impaired elimination of infection and death. We hypothesized that E coli preexposure impairs subsequent bacterial elimination as a consequence of Th2 differentiation and that interleukin-12 (IL-12) treatment could reverse this differentiation and minimize the effects of E coli preexposure. METHODS: After preexposure to E coli or other species, BALB/c mice or interferon-gamma (INF-gamma)-deficient mice, treated with or without IL-12, were given a standard intra-abdominal infection (E coli, Bacteroides fragilis, and adjuvant). Cohorts were killed for abscess quantification, in vitro T-cell proliferative responsiveness, and cytokine secretory profiles. Splenic lymphocytes preexposed in vivo to other types of bacteria were transferred to naive mice before intra-abdominal infection to determine whether preexposure, eliciting the lymphocyte-dependent response, was species specific. RESULTS: E coli preexposure alone caused no Th1 or Th2 shift; increased the proliferative responses of T cells; and, in combination with IL-12 therapy, caused markedly decreased IL-2 and IL-4 responses and an increased IFN-gamma response. IL-12 therapy did not change the response to intra-abdominal infection despite its ability to cause marked Th1 polarization. IFN-gamma-deficient mice responded to E coli preexposure no differently than did wild-type mice. Transfer of lymphocytes preexposed to Pseudomonas aeruginosa, Klebsiella pneumoniae, and hemolytic E coli but not other types of nosocomial pathogens caused the development of more abscesses just as transfer of E coli preexposed lymphocytes had. CONCLUSIONS: CD4+ T cells responsive to E coli preexposure regulate subsequent intra-abdominal abscess formation by a mechanism not explained by the Th1/Th2 paradigm. Preexposure to hemolytic E coli and other Enterobacteriaceae alters responses to intra-abdominal infection.

Intern call schedules and their relationship to sleep, operating room participation, stress, and satisfaction.

BACKGROUND: The ideal resident call schedule remains unknown. This study assessed the impact of different call schedules on intern performance and education. METHODS: A year-long, prospective, observational study of first-year residents in a surgery training program was performed with use of intern sleep/operative logs and questionnaires, and faculty questionnaires. RESULTS: Compared with interns taking call every third or fourth night (and cross-covering a separate service), interns taking call every other night reported the greatest amount of fatigue and stress, the lowest satisfaction, and the fewest operative cases. Errors in patient care were not different between schedules. Multivariate analysis revealed that operative participation was inversely related to frequency of night call and level of fatigue post call, stress was related to fatigue while off call and service census, and overall satisfaction was associated with infrequency of call and operative cases performed. Faculty reported more errors by interns cross-covering other services and less operating room participation by interns taking call every other night. CONCLUSIONS: No single resident schedule optimally balances patient care and resident education and satisfaction. All 3 patterns of call studied are acceptable; specific decisions regarding the allocation of house staff manpower should be flexible and dependent on individual service and educational needs.

The "July phenomenon" and the care of the severely injured patient: fact or fiction?

BACKGROUND: The "July phenomenon," a common belief in medical academia, refers to purported errors, inefficiency, and negative outcomes during the summertime transition of the house staff. We hypothesized that care in a trauma service is consistent throughout the year and that the July phenomenon therefore is a myth. METHODS: The records of adults admitted to a trauma service between July 1994 and September 1999 were evaluated. The care of and outcomes for patients admitted in July and August were compared with those of patients admitted in April and May. RESULTS: Nine hundred seventeen patients were evaluated over 5 years. Patients were well matched by the Injury Severity Score, the Glasgow Coma Score, by mechanism, and by survival probability. Patients admitted in the spring were significantly older, by a mean of 5.1 years. Length of stay and intensive care unit stay were similar. Emergency department times were similar, as were resuscitation times, infection rates, and hospital costs. The mortality of patients was similar between the 2 times. CONCLUSIONS: There was no evidence of an increase in negative outcomes early in the academic year compared with the end of the academic year. We believe that a systematic approach to the diagnosis, resuscitation, and treatment of trauma prevented a July phenomenon.

Transient and distant infections alter later intraperitoneal abscess formation.

Transient nosocomial infections, such as line sepsis and pneumonia, are common in today's critical care patient population. Although generally well treated, the effect of these transient antigen exposures on the immune system is unclear. We have previously shown that prior intraperitoneal inoculation with live bacteria leads to increased numbers of intraperitoneal abscesses. Data presented here demonstrate in a murine model that two immunizations with live Escherichia coli, Bacteroides fragilis, or both, administered systemically via intracardiac injection or at a focal distant site in subcutaneous tissue, significantly increased the number of mixed E coli/B fragilis intraperitoneal abscesses when induced 1 week later. Further, immunization with E coli, either alone or in combination with B fragilis, increased the total number of anaerobes recovered per mouse. Transient or focal sublethal infections can significantly alter an animal's immune response to later infectious insults, particularly the formation of intraperitoneal abscesses.

Analysis of aminoglycosides in the treatment of gram-negative infections in surgical patients.

HYPOTHESIS: Antibiotic regimens containing aminoglycosides result in a similar outcome compared with non-aminoglycoside regimens in the treatment of gram-negative infections in surgical patients. DESIGN: An inception cohort study of hospitalized surgical patients from December 1, 1996, through September 30, 1998. Patients were observed from the time of diagnosis of infection to discharge. SETTING: University hospital. PATIENTS: Two hundred fifty-eight consecutive gram-negative infections occurring in general surgical and trauma patients and patients undergoing transplantation. Sixty-six patients received aminoglycosides as a component of their treatment regimen, whereas 192 received other agents. RESULTS: Patients treated with aminoglycosides were younger (mean +/- SEM age, 48+/-2 vs 53+/-1 years; P = .04 by univariate analysis) and had a similar APACHE II (Acute Physiology and Chronic Health Evaluation II) score (mean +/- SEM, 17+/-1 vs 15+/-1; P = .10), yet had a significantly higher mortality vs patients treated with other agents (29% vs 14%; P = .02). A larger proportion of patients requiring hemodialysis were treated with aminoglycosides (33% vs 13%; P = .001). Although there was no difference in the sites of infection between groups, surgical patients with gram-negative pneumonia had a higher mortality when treated with aminoglycosides (37% vs 18%; P = .04), despite similar APACHE II scores (mean +/- SEM, 20+/-1 vs 18+/-1; P = .40). CONCLUSIONS: Despite a younger age and similar severity of illness, patients with gram-negative infections treated with aminoglycosides were associated with a higher mortality rate, although this may be related to selection bias in the use of aminoglycoside agents. The mortality rate associated with gram-negative pneumonia was also higher in patients treated with aminoglycosides, despite a similar severity of illness. Future randomized studies are necessary to reanalyze the role of aminoglycosides in treating surgical patients with gram-negative infections, particularly pneumonia.

Emerging evidence of selection of fluconazole-tolerant fungi in surgical intensive care units.

OBJECTIVE: To determine whether increased use of fluconazole has coincided with a shift in the relative proportion of fluconazole-tolerant species isolated from critically ill surgical patients in 2 university hospitals. DESIGN: Microbiological data and fluconazole administration frequencies were reviewed among patients treated in the surgical intensive care units (SICUs) from January 1, 1990, through December 31, 1995. SETTING: The SICUs of the University of Virginia Medical Center, Charlottesville, and the Hospital of the University of Pennsylvania, Philadelphia. MAIN OUTCOME MEASURES: The number and species types of all fungal isolates and the number of patients treated with fluconazole for each of the 6 years were determined. RESULTS: A sharp increase in the use of fluconazole among critically ill surgical patients has occurred at both medical centers from 1990-1995. The culture results of most patients treated with fluconazole were negative for fungi (73% and 63% at the University of Virginia Medical Center and the Hospital of the University of Pennsylvania, respectively); there was a greater tendency to use fluconazole at the University of Virginia Medical Center compared with the Hospital of the University of Pennsylvania (2.2% vs 1.8% of patients admitted to the SICU received it, respectively; P = .007). There was a significant increase in the proportion of Candida glabrata isolated at the University of Virginia Medical Center (P < .01) from 1990-1995, but a similar change was not detectable at the Hospital of the University of Pennsylvania. CONCLUSIONS: These data justify concern that the increased use of fluconazole in SICUs may be promoting a shift in the fungal flora that cause nosocomial infections toward species that are more difficult to treat. Prospective studies about the use of fluconazole for prophylaxis and empirical therapy among SICU patients are warranted before its widespread use in these settings continues.

Anti-tumor necrosis factor antibody reduces mortality in the presence of antibiotic-induced tumor necrosis factor release.

The systemic tumor necrosis factor (TNF) response has been extensively studied during infection. In addition, antibiotics that cause cell-wall lysis have been associated with endotoxinemia and, therefore, could trigger TNF release. We studied the effects of pretreatment with cefoxitin and/or anti-TNF antibody on mortality and early (90 minutes) and delayed (6 hours) serum TNF levels in a murine model of mixed Escherichia coli/Bacteroides fragilis peritonitis. At low and intermediate inocula levels, cefoxitin, but not anti-TNF antibody, prevented death, and low serum TNF levels were noted in all groups. At the highest inoculum level, mortality was uniform in control, cefoxitin, and anti-TNF antibody groups, and a significant elevation in serum TNF levels was seen only at the 6-hour point in animals receiving cefoxitin. The addition of anti-TNF antibody to cefoxitin at this inoculum level abrogated the 6-hour rise in serum TNF levels and reduced mortality to 40%. These results emphasize that the cytokine response in disease is dependent on both the nature of the insult and other forms of therapeutic interventions.

Waiting for microbiologic data to direct therapy against nosocomial infections in febrile surgical patients: are outcomes worsened?

HYPOTHESIS: Allowing adequate time for laboratory and culture results before initial treatment may be associated with a worse outcome in nosocomial infections. DESIGN: Cohort study of all episodes of nosocomial infection from December 10, 1996, to October 28, 1998. SETTING: Surgical services at a university hospital. PATIENTS AND METHODS: In surgical patients presenting with fever, 372 episodes of nosocomial infection were evaluated. Nosocomial infections were divided by time from fever to intervention (< or =12, 13-24, and >24 hours). These groups were subdivided by Acute Physiology and Chronic Health Evaluation II (APACHE II) scores into low (< or =10 [n = 114]), moderate (11-20 [n = 169]), and high severity of illness (>20 [n = 89]). Pneumonia and bloodstream infections were divided by APACHE II scores into low (< or =15 [n = 55 and n = 56, respectively]) or high severity of illness (>15 [n = 84 and n = 77, respectively]). MAIN OUTCOME MEASURES: Mortality, length of stay. RESULTS: No difference in outcome was seen between different time intervals from fever to intervention for nosocomial infections in patients with APACHE II scores of no more than 10. Patients treated more than 24 hours after fever were significantly younger than those treated at no more than 12 and 13 to 24 hours with APACHE II scores of 11 to 20 (P<.05) and more than 20 (P<.05). Mortality and length of stay for patients treated at later time intervals were comparable with those of patients treated earlier with similar APACHE II scores. There was no difference in outcome for patients with pneumonia or bloodstream infection. CONCLUSIONS: Episodes of infection in which treatment was withheld until initial microbiologic data were available (24 hours) did not have worse outcomes compared with those treated earlier. Waiting for laboratory and culture results to direct antibiotic therapy for nosocomial infections does not appear harmful and may be potentially beneficial.