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Background and Objective: The antiretroviral nevirapine can cause severe hepatotoxicity when used 'off-label' for preventing mother-to-child HIV transmission (PMTCT), newborn post-exposure prophylaxis and for pre- and post-exposure prophylaxis among non-HIV-infected individuals. We describe the incidence of hepatotoxicity with short- versus long-course nevirapine-containing regimens in these groups.Methods: We reviewed hepatotoxicity cases among non-HIV-infected individuals and HIV-infected pregnant women and their offspring receiving short- (or=5 days) nevirapine prophylaxis. Sources included adverse event reports from pharmaceutical manufacturers and the US FDA, reports from peer-reviewed journals/scientific meetings and the Research on Adverse Drug events And Reports (RADAR) project. Hepatotoxicity was scored using the AIDS Clinical Trial Group criteria.Results: Toxicity data for 8216 patients treated with nevirapine-containing regimens were reviewed. Among 402 non-HIV-infected individuals receiving short- (n=251) or long-course (n=151) nevirapine, rates of grade 1-2 hepatotoxicity were 1.99% versus 5.30%, respectively, and rates of grade 3-4 hepatotoxicity were 0.00% versus 13.25%, respectively (p<0.001 for both comparisons). Among 4740 HIV-infected pregnant women receiving short- (n=3031) versus long-course (n=1709) nevirapine, rates of grade 1-2 hepatotoxicity were 0.62% and 7.04%, respectively, and rates of grade 3-4 hepatotoxicity were 0.23% versus 4.39%, respectively (p<0.001 for both comparisons). The rates of grade 3-4 hepatotoxicity among 3074 neonates of nevirapine-exposed HIV-infected pregnant women were 0.8% for those receiving short-course (n=2801) versus 1.1% for those receiving long-course (n=273) therapy (p<0.72).Conclusions: Therapy duration appears to significantly predict nevirapine hepatotoxicity. Short-course nevirapine for HIV prophylaxis is associated with fewer hepatotoxic reactions for non-HIV-infected individuals or pregnant HIV-infected women and their offspring, but administration of prophylactic nevirapine for >or=2 weeks appears to be associated with high rates of hepatotoxicity among non-HIV-infected individuals and HIV-infected pregnant mothers. When full highly active antiretroviral therapy (HAART) regimens are not available, single-dose nevirapine plus short-course nucleoside reverse transcriptase inhibitors to decrease the development of HIV viral resistance is an essential therapeutic option for PMTCT and these data support the safety of single-dose nevirapine in this setting. [ABSTRACT FROM AUTHOR]

Although healthy lifestyles are related to improved quality of life in the general population, little is known about the role of healthy lifestyles during HIV infection. The authors examined the relationships between health-promoting behaviors, risk behaviors, stress, and health-related quality of life (HRQOL) among 226 men with HIV infection who were attending three infectious disease clinics. As hypothesized, health-promoting behaviors were positively related and stress was negatively related with most of the HRQOL dimensions. Contrary to the hypothesis, tobacco use, recreational drug use, and unsafe sexual behaviors were not related to the HRQOL dimensions. Hazardous alcohol use was negatively associated with one HRQOL dimension-social functioning. The association of modifiable factors, such as health-promoting behaviors and stress, with HQROL offers opportunities for improving HIV-related health care. Relatively simple, straightforward changes in lifestyles such as eating well, remaining active, and avoiding stressful life events may result in improvements in HRQOL. [ABSTRACT FROM AUTHOR]

Study Objectives: We evaluated differences in processes and outcomes of HIV-related pneumonia care among patients in Veterans Affairs (VA), public, and for-profit and not-for-profit private hospitals in the United States. We compared the results of our current study (1995 to 1997) with those of our previous study that included a sample of patients receiving care during the years 1987 to 1990 to determine how HIV-related pneumonia care had evolved over the last decade.Setting/patients: The sample consisted of 1,231 patients with HIV infection who received care for Pneumocystis carinii pneumonia (PCP) and 750 patients with HIV infection who received care for community-acquired pneumonia (CAP) during the years 1995 to 1997.Measurement: We conducted a retrospective medical record review and evaluated patient and hospital characteristics, HIV-related processes of care (timely use of anti-PCP medications, adjunctive corticosteroids), non-HIV-related processes of care (timely use of CAP treatment medications, diagnostic testing, ICU utilization, rates of endotracheal ventilation, placement on respiratory isolation), length of inpatient hospital stay, and inpatient mortality.Results: Rates of timely use of antibiotics and adjunctive corticosteroids for treating PCP were high and improved dramatically from the prior decade. However, compliance with consensus guidelines that recommend < 8 h as the optimal time window for initiation of antibiotics to treat CAP was lower. For both PCP and CAP, variations in processes of care and lengths of in-hospital stays, but not mortality rates, were noted at VA, public, private not-for-profit hospitals, and for-profit hospitals.Conclusions: This study provides the first overview of HIV-related pneumonia care in the early highly active antiretroviral therapy era, and contrasts current findings with those of a similarly conducted study from a decade earlier. Quality of care for patients with PCP improved, but further efforts are needed to facilitate the appropriate management of CAP. In the third decade of the epidemic, it will be important to monitor whether variations in processes of care for various HIV-related clinical diagnoses among different types of hospitals persist. [ABSTRACT FROM AUTHOR]

The impact of chronic indwelling urinary catheters (IUCs) on the composition and stability of the urinary microbiota remains unknown. The primary aim of this study was to describe the urinary microbiomes of geriatric males with chronic IUCs. A secondary aim was to explore clinical catheter-associated urinary tract infection (CAUTI) courses of the participants. Geriatric male patients with chronic IUCs were followed longitudinally. Catheterized urine, catheter tips, and both urethral and periurethral swabs were collected from participants at monthly intervals. Microbes were isolated and identified from each specimen using an enhanced culture method called expanded quantitative urine culture (EQUC) and targeted 16S rRNA gene DNA sequencing. Microbial outcomes were examined both in the absence of urinary symptoms and in the context of clinical diagnosis of CAUTI. Ten male participants (mean age 86 years) were enrolled. Urinary microbiomes differed for each participant. However, within each individual, microbiomes were similar over time and across niches (bladder, catheter, urethra, and periurethra). Within-niche microbiomes differed across individuals, and this was observed over time. The most abundant bacteria isolated from all niches were known uropathogens. Six of 10 individuals met diagnostic criteria for CAUTI at least once during the 12-month observation period, but no evidence of this or antibiotic treatment/response was discernable in our monthly samples. The microbiomes of each participant were unique and remained similar over time and across niches. Longitudinal EQUC or 16S rRNA gene sequencing data could be useful to clinicians when diagnosing or treating possible CAUTI.IMPORTANCECatheter-associated urinary tract infections (CAUTIs) are serious but preventable nosocomial infections. The most common risk factor for developing CAUTI is prolonged use of indwelling urinary catheters (IUCs). This study provides the first longitudinal description of the urinary microbiomes of geriatric males with chronic IUCs, in the absence of urinary signs and symptoms, as a first step toward enhancing our knowledge of the impact of chronic IUCs on the composition and stability of the urinary microbiota. This is an understudied area, particularly for males., Competing Interests: A.J.W. discloses membership on the Scientific Advisory Boards of Urobiome Therapeutics and Pathnostics. He also discloses funding from the Craig H. Neilsen Foundation, Pathnostics, and an anonymous donor. J.P.P. discloses membership on the Shionogi and Innoviva speaker's bureaus. The other authors have no relevant disclosures.

Background/Objective: SeptiCyte RAPID is a transcriptional host response assay that discriminates between sepsis and non-infectious systemic inflammation (SIRS) with a one-hour turnaround time. The overall performance of this test in a cohort of 419 patients has recently been described [Balk et al., J Clin Med 2024, 13, 1194]. In this study, we present the results from a detailed stratification analysis in which SeptiCyte RAPID performance was evaluated in the same cohort across patient groups and subgroups encompassing different demographics, comorbidities and disease, sources and types of pathogens, interventional treatments, and clinically defined phenotypes. The aims were to identify variables that might affect the ability of SeptiCyte RAPID to discriminate between sepsis and SIRS and to determine if any patient subgroups appeared to present a diagnostic challenge for the test. Methods: (1) Subgroup analysis, with subgroups defined by individual demographic or clinical variables, using conventional statistical comparison tests. (2) Principal component analysis and k-means clustering analysis to investigate phenotypic subgroups defined by unique combinations of demographic and clinical variables. Results: No significant differences in SeptiCyte RAPID performance were observed between most groups and subgroups. One notable exception involved an enhanced SeptiCyte RAPID performance for a phenotypic subgroup defined by a combination of clinical variables suggesting a septic shock response. Conclusions: We conclude that for this patient cohort, SeptiCyte RAPID performance was largely unaffected by key variables associated with heterogeneity in patients suspected of sepsis.

Objective: To determine the effectiveness of active, upper-room, germicidal ultraviolet (GUV) devices in reducing bacterial contamination in patient rooms in air and on surfaces as a supplement to the central heating, ventilation, and air conditioning (HVAC) air handling unit (AHU) with MERV 14 filters and UV-C disinfection., Methods: This study was conducted in an academic medical center, burn intensive care unit (BICU), for 4 months in 2022. Room occupancy was monitored and recorded. In total, 402 preinstallation and postinstallation bacterial air and non-high-touch surface samples were obtained from 10 BICU patient rooms. Airborne particle counts were measured in the rooms, and bacterial air samples were obtained from the patient-room supply air vents and outdoor air, before and after the intervention. After preintervention samples were obtained, an active, upper-room, GUV air disinfection system was deployed in each of the patient rooms in the BICU., Results: The average levels of airborne bacteria of 395 CFU/m 3 before GUV device installation and 37 CFU/m 3 after installation indicated an 89% overall decrease ( P < .0001). Levels of surface-borne bacteria were associated with a 69% decrease ( P < .0001) after GUV device installation. Outdoor levels of airborne bacteria averaged 341 CFU/m 3 in March before installation and 676 CFU/m 3 in June after installation, but this increase was not significant ( P = .517)., Conclusions: Significant reductions in air and surface contamination occurred in all rooms and areas and were not associated with variations in outdoor air concentrations of bacteria. The significant decrease of surface bacteria is an unexpected benefit associated with in-room GUV air disinfection, which can potentially reduce overall bioburden.

(1) Background: SeptiCyte RAPID is a molecular test for discriminating sepsis from non-infectious systemic inflammation, and for estimating sepsis probabilities. The objective of this study was the clinical validation of SeptiCyte RAPID, based on testing retrospectively banked and prospectively collected patient samples. (2) Methods: The cartridge-based SeptiCyte RAPID test accepts a PAXgene blood RNA sample and provides sample-to-answer processing in ~1 h. The test output (SeptiScore, range 0-15) falls into four interpretation bands, with higher scores indicating higher probabilities of sepsis. Retrospective (N = 356) and prospective (N = 63) samples were tested from adult patients in ICU who either had the systemic inflammatory response syndrome (SIRS), or were suspected of having/diagnosed with sepsis. Patients were clinically evaluated by a panel of three expert physicians blinded to the SeptiCyte test results. Results were interpreted under either the Sepsis-2 or Sepsis-3 framework. (3) Results: Under the Sepsis-2 framework, SeptiCyte RAPID performance for the combined retrospective and prospective cohorts had Areas Under the ROC Curve (AUCs) ranging from 0.82 to 0.85, a negative predictive value of 0.91 (sensitivity 0.94) for SeptiScore Band 1 (score range 0.1-5.0; lowest risk of sepsis), and a positive predictive value of 0.81 (specificity 0.90) for SeptiScore Band 4 (score range 7.4-15; highest risk of sepsis). Performance estimates for the prospective cohort ranged from AUC 0.86-0.95. For physician-adjudicated sepsis cases that were blood culture (+) or blood, urine culture (+)(+), 43/48 (90%) of SeptiCyte scores fell in Bands 3 or 4. In multivariable analysis with up to 14 additional clinical variables, SeptiScore was the most important variable for sepsis diagnosis. A comparable performance was obtained for the majority of patients reanalyzed under the Sepsis-3 definition, although a subgroup of 16 patients was identified that was called septic under Sepsis-2 but not under Sepsis-3. (4) Conclusions: This study validates SeptiCyte RAPID for estimating sepsis probability, under both the Sepsis-2 and Sepsis-3 frameworks, for hospitalized patients on their first day of ICU admission.

Background: Postoperative infectious complications after a pancreaticoduodenectomy remain a significant cause of morbidity. Studies have demonstrated that a preoperative biliary stent increases the risk of postoperative infectious complications. Few studies have investigated the specific preoperative biliary stent bacterial sensitivities to preoperative antibiotics and the effect on infectious complications. The goal of this study was to investigate if the presence of a preoperative biliary stent increases the risk of postoperative infectious complications in patients undergoing a pancreaticoduodenectomy. Additionally, we aimed to investigate biliary stent culture sensitivities to preoperative antibiotics and determine if those sensitivities impacted postoperative infectious complications after a pancreaticoduodenectomy., Methods: A retrospective chart review of patients who had undergone a pancreaticoduodenectomy at a single institution tertiary care center from 2007 to 2018 was performed. Perioperative variables including microbiology cultures from biliary stents were collected and analyzed., Results: A total of 244 patients underwent a pancreaticoduodenectomy. A preoperative biliary stent was present in 45 (18%) patients. Infectious complications occurred in 25% of those patients with a preoperative biliary stent, and 19% of those without (P = .37). Of those patients with a stent that was cultured intraoperatively, 92% grew bacteria and 61% of those were resistant to the preoperative antibiotics administered. Of the patients with a preoperative biliary stent and bacteria resistant to the preoperative antibiotics, 17% developed a postoperative infectious complication, compared with 20% if the bacteria cultured was susceptible to the preoperative antibiotics (P = .64)., Conclusion: Infectious complications after pancreaticoduodenectomy are a significant cause of morbidity. Stent bacterial sensitivities to preoperative antibiotics did not reduce the postoperative infectious complications in the preoperative biliary stent group suggesting a multifactorial cause of infections., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Catheter-associated asymptomatic bacteriuria (CAABU) is frequent in intensive care units (ICUs) and contributes to the routine use of antibiotics and to antibiotic-resistant infections. While nurses are responsible for the implementation of CAABU-prevention guidelines, variability in how individual nurses contribute to CAABU-free rates in ICUs has not been previously explored. This study's objective was to examine the variability in CAABU-free outcomes of individual ICU nurses. This observational cross-sectional study used shift-level nurse-patient data from the electronic health records from two ICUs in a tertiary medical center in the US between July 2015 and June 2016. We included all adult (18+) catheterized patients with no prior CAABU during the hospital encounter and nurses who provided their care. The CAABU-free outcome was defined as a 0/1 indicator identifying shifts where a previously CAABU-free patient remained CAABU-free (absence of a confirmed urine sample) 24-48 hours following end of shift. The analytical approach used Value-Added Modeling and a split-sample design to estimate and validate nurse-level CAABU-free rates while adjusting for patient characteristics, shift, and ICU type. The sample included 94 nurses, 2,150 patients with 256 confirmed CAABU cases, and 21,729 patient shifts. Patients were 55% male, average age was 60 years. CAABU-free rates of individual nurses varied between 94 and 100 per 100 shifts (Wald test: 227.88, P<0.001) and were robust in cross-validation analyses (correlation coefficient: 0.66, P<0.001). Learning and disseminating effective CAABU-avoidance strategies from top-performers throughout the nursing teams could improve quality of care in ICUs., Competing Interests: The authors have declared that no competing interests exist.

Background: Differentiating sepsis from the systemic inflammatory response syndrome (SIRS) in critical care patients is challenging, especially before serious organ damage is evident, and with variable clinical presentations of patients and variable training and experience of attending physicians. Our objective was to describe and quantify physician agreement in diagnosing SIRS or sepsis in critical care patients as a function of available clinical information, infection site, and hospital setting., Methods: We conducted a post hoc analysis of previously collected data from a prospective, observational trial ( N  = 249 subjects) in intensive care units at seven US hospitals, in which physicians at different stages of patient care were asked to make diagnostic calls of either SIRS, sepsis, or indeterminate, based on varying amounts of available clinical information (clinicaltrials.gov identifier: NCT02127502). The overall percent agreement and the free-marginal, inter-observer agreement statistic kappa ( κ free ) were used to quantify agreement between evaluators (attending physicians, site investigators, external expert panelists). Logistic regression and machine learning techniques were used to search for significant variables that could explain heterogeneity within the indeterminate and SIRS patient subgroups., Results: Free-marginal kappa decreased between the initial impression of the attending physician and (1) the initial impression of the site investigator ( κ free 0.68), (2) the consensus discharge diagnosis of the site investigators ( κ free 0.62), and (3) the consensus diagnosis of the external expert panel ( κ free 0.58). In contrast, agreement was greatest between the consensus discharge impression of site investigators and the consensus diagnosis of the external expert panel ( κ free 0.79). When stratified by infection site, κ free for agreement between initial and later diagnoses had a mean value + 0.24 (range - 0.29 to + 0.39) for respiratory infections, compared to + 0.70 (range + 0.42 to + 0.88) for abdominal + urinary + other infections. Bioinformatics analysis failed to clearly resolve the indeterminate diagnoses and also failed to explain why 60% of SIRS patients were treated with antibiotics., Conclusions: Considerable uncertainty surrounds the differential clinical diagnosis of sepsis vs. SIRS, especially before organ damage has become highly evident, and for patients presenting with respiratory clinical signs. Our findings underscore the need to provide physicians with accurate, timely diagnostic information in evaluating possible sepsis., Competing Interests: Ethics approval was gained from the relevant institutional review boards: Intermountain Medical Center/Latter Day Saints Hospital (1024931); Johns Hopkins Hospital (IRB00087839); Rush University Medical Center (15111104-IRB01); Loyola University Medical Center (208291); Northwell Healthcare (16-02-42-03); and Grady Memorial Hospital (000-87806).This manuscript does not contain any individual person’s data in any form. Therefore, consent for publication is not required.The authors have read the journal’s policy and declare the following competing interests: LM, TDY, AR, RBB, RAB, and TS are current or past employees and/or shareholders of Immunexpress.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Background: There have been reported outbreaks of carbapenem-resistant Enterobacteriaceae infections linked to endoscopes with elevator mechanisms. Adenosine triphosphate (ATP) testing has been used as a marker for bioburden and monitoring manual cleaning for flexible endoscopes with and without an elevator mechanism. The objective of this study was to determine whether routine ATP testing could identify areas of improvement in cleaning of endoscopes with an elevator mechanism., Methods: ATP testing after manual cleaning of TJF-Q180V duodenoscopes and GF-UCT180 linear echoendoscopes (Olympus America Inc, Center Valley, PA) was implemented. Samples were tested from the distal end, the elevator mechanism, and water flushed through the lumen of the biopsy channel. Data were recorded and compared by time point, test point, and reprocessing technician., Results: Overall failure rate was 6.99% (295 out of 4,219). The highest percentage of failed ATP tests (17.05%) was reported in the first quarter of routine testing, with an overall decrease in rates over time. The elevator mechanism and working channel lumen had higher failure rates than the distal end. Quality of manual cleaning between reprocessing technicians showed variation., Conclusion: ATP testing is effective in identifying residual organic material and improving quality of manual cleaning of endoscopes with an elevator mechanism. Cleaning efficacy is influenced by reprocessing technicians and location tested on the endoscope. Close attention to the working channel and elevator mechanism during manual cleaning is warranted., (Copyright © 2018 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Rationale: A molecular test to distinguish between sepsis and systemic inflammation of noninfectious etiology could potentially have clinical utility., Objectives: This study evaluated the diagnostic performance of a molecular host response assay (SeptiCyte LAB) designed to distinguish between sepsis and noninfectious systemic inflammation in critically ill adults., Methods: The study employed a prospective, observational, noninterventional design and recruited a heterogeneous cohort of adult critical care patients from seven sites in the United States (n = 249). An additional group of 198 patients, recruited in the large MARS (Molecular Diagnosis and Risk Stratification of Sepsis) consortium trial in the Netherlands ( www.clinicaltrials.gov identifier NCT01905033), was also tested and analyzed, making a grand total of 447 patients in our study. The performance of SeptiCyte LAB was compared with retrospective physician diagnosis by a panel of three experts., Measurements and Main Results: In receiver operating characteristic curve analysis, SeptiCyte LAB had an estimated area under the curve of 0.82-0.89 for discriminating sepsis from noninfectious systemic inflammation. The relative likelihood of sepsis versus noninfectious systemic inflammation was found to increase with increasing test score (range, 0-10). In a forward logistic regression analysis, the diagnostic performance of the assay was improved only marginally when used in combination with other clinical and laboratory variables, including procalcitonin. The performance of the assay was not significantly affected by demographic variables, including age, sex, or race/ethnicity., Conclusions: SeptiCyte LAB appears to be a promising diagnostic tool to complement physician assessment of infection likelihood in critically ill adult patients with systemic inflammation. Clinical trial registered with www.clinicaltrials.gov (NCT01905033 and NCT02127502).

Study Objectives: The primary objective was to determine the impact of hematologic malignancies and/or conditioning regimens on the risk of developing Clostridium difficile infection (CDI) in patients undergoing hematopoietic stem cell transplantation (HSCT). Secondary objectives were to determine if traditional CDI risk factors applied to patients undergoing HSCT and to determine the presence of CDI markers of severity of illness among this patient population., Design: Single-center retrospective case-control study., Setting: Quaternary care academic medical center., Patients: A total of 105 patients who underwent HSCT between December 2009 and December 2014; of these patients, 35 developed an initial episode of CDI (HSCT/CDI group [cases]), and 70 did not (controls). Controls were matched in a 2:1 ratio to cases based on age (± 10 yrs) and date of HSCT (± 6 mo)., Measurements and Main Results: Baseline characteristics of the two groups were well balanced regarding age, sex, race, ethnicity, and type of HSCT. No significant differences in conditioning regimen, hematologic malignancy, total body irradiation received for HSCT, use of antibiotics within 60 days of HSCT, or use of prophylactic antibiotics after HSCT were noted between the two groups. Patients in the control group were 10.57 (95% confidence interval 1.24-492.75) more likely to have received corticosteroids prior to HSCT than patients in the HSCT/CDI group (p=0.01). Use of proton pump inhibitors at the time of HSCT was greater among the control group than among patients in the HSCT/CDI group (97% vs 86%, p=0.048). No significant difference in mortality was noted between the groups at 3, 6, and 12 months after HSCT. Metronidazole was frequently prescribed for patients in the HSCT/CDI group (34 patients [97%]). Severe CDI was not common among patients within the HSCT/CDI group (13 patients [37%]); vancomycin was infrequently prescribed for these patients ([31%] 4/13 patients)., Conclusion: Hematologic malignancies and a conditioning regimen administered for HSCT were not significant risk factors for the development of CDI after HSCT. Use of corticosteroids prior to HSCT and use of proton pump inhibitors at the time of HSCT were associated with a significantly decreased risk of CDI., (© 2017 Pharmacotherapy Publications, Inc.)

Background: Rotavirus infection in adults is poorly understood and few rotavirus outbreaks among US adults have been reported in the literature. We describe an outbreak due to genotype G12P[8] rotavirus among medical students, faculty, and guests who attended a formal dinner event in April 2013., Methods: A web-based questionnaire was distributed to event attendees to collect symptom and exposure data. A clinical case was defined as a person who developed diarrhea after attending the formal event. A laboratory-confirmed case was defined as a clinical case who attended the formal event, with rotavirus detected in stool by enzyme immunoassay or reverse transcription-polymerase chain reaction (RT-PCR) assay., Results: Among 334 dinner attendees, 136 (41%) completed the web-based questionnaire; 58 (43%) respondents reported illness. Symptom onset ranged from 1 to 8 days, with peak onset 3 days after the event. In addition to diarrhea, predominant symptoms included fever (91%), abdominal pain (84%), and vomiting (49%). The median duration of illness was 2.5 days. Thirteen (22%) of 58 cases sought medical attention; none were hospitalized. Analysis of food exposures among questionnaire respondents did not identify significant associations between any specific food or drink item and illness. Stool specimens were negative for bacterial pathogens by culture and negative for norovirus by RT-PCR assay; 4 specimens were positive for rotavirus by enzyme immunoassay or PCR. G12P[8]-R1-C1-M1-A1-N1-T1-E1-H1 was identified as the causative full-genome genotype., Conclusions: Rotavirus outbreaks can occur among adults, including young adults. Health professionals should consider rotavirus as a cause of acute gastroenteritis in adults., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Rapid public health response to a large-scale anthrax attack would reduce overall morbidity and mortality. However, there is uncertainty about the optimal cost-effective response strategy based on timing of intervention, public health resources, and critical care facilities. We conducted a decision analytic study to compare response strategies to a theoretical large-scale anthrax attack on the Chicago metropolitan area beginning either Day 2 or Day 5 after the attack. These strategies correspond to the policy options set forth by the Anthrax Modeling Working Group for population-wide responses to a large-scale anthrax attack: (1) postattack antibiotic prophylaxis, (2) postattack antibiotic prophylaxis and vaccination, (3) preattack vaccination with postattack antibiotic prophylaxis, and (4) preattack vaccination with postattack antibiotic prophylaxis and vaccination. Outcomes were measured in costs, lives saved, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). We estimated that postattack antibiotic prophylaxis of all 1,390,000 anthrax-exposed people beginning on Day 2 after attack would result in 205,835 infected victims, 35,049 fulminant victims, and 28,612 deaths. Only 6,437 (18.5%) of the fulminant victims could be saved with the existing critical care facilities in the Chicago metropolitan area. Mortality would increase to 69,136 if the response strategy began on Day 5. Including postattack vaccination with antibiotic prophylaxis of all exposed people reduces mortality and is cost-effective for both Day 2 (ICER=$182/QALY) and Day 5 (ICER=$1,088/QALY) response strategies. Increasing ICU bed availability significantly reduces mortality for all response strategies. We conclude that postattack antibiotic prophylaxis and vaccination of all exposed people is the optimal cost-effective response strategy for a large-scale anthrax attack. Our findings support the US government's plan to provide antibiotic prophylaxis and vaccination for all exposed people within 48 hours of the recognition of a large-scale anthrax attack. Future policies should consider expanding critical care capacity to allow for the rescue of more victims.

Background: Bartonella henselae (B. henselae) is considered a rare cause of granulomatous hepatitis. Due to the fastidious growth characteristics of the bacteria, the limited sensitivity of histopathological stains, and the non-specific histological findings on liver biopsy, the diagnosis of hepatic bartonellosis can be difficult to establish. Furthermore, the optimal treatment of established hepatic bartonellosis remains controversial., Case Presentation: We present a case of hepatic bartonellosis in an immunocompetent woman who presented with right upper quadrant pain and a five cm right hepatic lobe mass on CT scan. The patient underwent a right hepatic lobectomy. Surgical pathology revealed florid necrotizing granulomatous hepatitis, favoring an infectious etiology. Despite extensive histological and serological evaluation a definitive diagnosis was not established initially. Thirteen months after initial presentation, hepatic bartonellosis was diagnosed by PCR studies from surgically excised liver tissue. Interestingly, the hepatic granulomas persisted and Bartonella henselae was isolated from the patient's enriched blood culture after several courses of antibiotic therapy., Conclusion: The diagnosis of hepatic bartonellosis is exceedingly difficult to establish and requires a high degree of clinical suspicion. Recently developed, PCR-based approaches may be required in select patients to make the diagnosis. The optimal antimicrobial therapy for hepatic bartonellosis has not been established, and close follow-up is needed to ensure successful eradication of the infection.

Objective: To describe the identification, management, and clinical characteristics of hospitalized patients with influenza-like illness (ILI) during the peak period of activity of the 2009 pandemic strain of influenza A virus subtype H1N1 (2009 H1N1)., Design: Retrospective review of electronic medical records., Patients and Setting: Hospitalized patients who presented to the emergency department during the period October 18 through November 14, 2009, at 4 hospitals in Cook County, Illinois, with the capacity to perform real-time reverse-transcriptase polymerase chain reaction testing for influenza., Methods: Vital signs and notes recorded within 1 calendar day after emergency department arrival were reviewed for signs and symptoms consistent with ILI. Cases of ILI were classified as recognized by healthcare providers if an influenza test was performed or if influenza was mentioned as a possible diagnosis in the physician notes. Logistic regression was used to determine the patient attributes and symptoms that were associated with ILI recognition and with influenza infection., Results: We identified 460 ILI case patients, of whom 412 (90%) had ILI recognized by healthcare providers, 389 (85%) were placed under airborne or droplet isolation precautions, and 243 (53%) were treated with antiviral medication. Of 401 ILI case patients tested for influenza, 91 (23%) had a positive result. Fourteen (3%) ILI case patients and none of the case patients who tested positive for influenza had sore throat in the absence of cough., Conclusions: Healthcare providers identified a high proportion of hospitalized ILI case patients. Further improvements in disease detection can be made through the use of advanced electronic health records and efficient diagnostic tests. Future studies should evaluate the inclusion of sore throat in the ILI case definition.

Although respiratory viral infections have been associated with acute rejection and bronchiolitis obliterans syndrome, the long-term impact of the novel pandemic influenza A (2009 H1N1) virus on lung transplant patients has not been defined. We describe the diagnostic challenges and long-term consequences of 2009 H1N1 infection in a lung transplant patient, discuss the potential implications for prevention and treatment, and conclude that even timely antiviral therapy may be insufficient to prevent long-term morbidity., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Background: Alcohol-based hand rubs (ABHRs) are an effective means of decreasing the transmission of bacterial pathogens. Alcohol is not effective against Clostridium difficile spores. We examined the retention of C. difficile spores on the hands of volunteers after ABHR use and the subsequent transfer of these spores through physical contact., Methods: Nontoxigenic C. difficile spores were spread on the bare palms of 10 volunteers. Use of 3 ABHRs and chlorhexidine soap-and-water washing were compared with plain water rubbing alone for removal of C. difficile spores. Palmar cultures were performed before and after hand decontamination by means of a plate stamping method. Transferability of C. difficile after application of ABHR was tested by having each volunteer shake hands with an uninoculated volunteer., Results: Plain water rubbing reduced palmar culture counts by a mean (+/- standard deviation [SD]) of 1.57 +/- 0.11 log10 colony-forming units (CFU) per cm2, and this value was set as the zero point for the other products. Compared with water washing, chlorhexidine soap washing reduced spore counts by a mean (+/- SD) of 0.89 +/- 0.34 log10 CFU per cm2; among the ABHRs, Isagel accounted for a reduction of 0.11 +/- 0.20 log10 CFU per cm2 (P = .005), Endure for a reduction of 0.37 +/- 0.42 log10 CFU per cm2 (P = .010), and Purell for a reduction of 0.14 +/- 0.33 log10 CFU per cm2 (P = .005). There were no statistically significant differences between the reductions achieved by the ABHRs; only Endure had a reduction statistically different from that for water control rubbing (P = .040). After ABHR use, handshaking transferred a mean of 30% of the residual C. difficile spores to the hands of recipients., Conclusions: Hand washing with soap and water is significantly more effective at removing C. difficile spores from the hands of volunteers than are ABHRs. Residual spores are readily transferred by a handshake after use of ABHR.

Few reports in the literature have documented 'spontaneous' vertebral osteomyelitis due to Staphylococcus epidermidis. Herein, we describe a case of S. epidermidis lumbar osteomyelitis presenting as progressive back pain, but without a known port of entry or underlying pre-existing high-risk predisposing conditions. A low threshold for the consideration of infectious osteomyelitis is warranted in persons presenting with new, progressive back pain.

Racial disparities in HIV-care include the disproportionate impact of HIV/AIDS on African Americans. We conducted a retrospective review of 1,855 cases at 78 hospitals in nine cities to evaluate racial variations in inpatient care for AIDS-related Pneumocystis pneumonia (PCP) shortly after the introduction of highly active anti-retroviral therapies. While inpatient HIV-related PCP mortality was comparable between Whites and Hispanics (p=0.94), African Americans were less likely than Whites to die in-hospital (AOR 0.69, 95% CI 0.48, 0.99) and more likely to receive timely anti-PCP medications (AOR 1.67, 95% CI 1.21, 2.30) and timely corticosteroids (AOR 1.46, 95% CI 1.17, 1.82). Findings were compared with those from our study involving 1,547 patients at 82 hospitals in five cities over the first decade of the AIDS epidemic. In contrast to the first study, in the second decade African Americans were more likely to receive timely and appropriate therapy for HIV-related PCP, and resultantly were more likely to survive the hospitalization.

Background: The molecular epidemiology of endemic and outbreak Clostridium difficile strains across time is not well known., Methods: HindIII restriction endonuclease analysis (REA) typing was performed on available clinical C. difficile isolates from 1982 to 1991., Results: The annual incidence of C. difficile infection (CDI) ranged from 3.2 to 9.9 cases per 1000 discharges and was significantly higher in 1982, 1983, 1985, and 1991 (high-incidence years) than in other years (mean standard deviation number of cases for the high- vs the low-incidence years, 121.8 +/-20.4 and 70.0 +/-15.0; P =.002). A total of 696 (76.6%) of 908 C. difficile isolates were available for REA typing over the 10-year period. Large clusters (>or=10 CDI cases in consecutive months) were caused by REA types B1 and B2 in 1982 and 1983, F2 and B1 in 1985, and K1 in 1991 (high-incidence years). Small clusters of 4-9 CDI cases in consecutive months were caused by REA types G1 (1984), Y4 and Y6 (1987), Y2 (1988), L1 (1989), Y1 (1990), and K1 (1991). Current epidemic REA group BI (unrelated to type B1) was isolated 6 times, twice in 1984, 1988, and 1990., Conclusions: Years with a high incidence of CDI were associated with large clusters of specific REA types that changed yearly. The molecular epidemiology of CDI in this hospital was characterized by a wide diversity of C. difficile types and an ever-changing dominance of specific C. difficile types over time. The current epidemic BI group was found sporadically on 6 occasions. A changing CDI molecular epidemiology should be expected in the future.

All patients admitted to our tertiary care hospital from 1 December 2007 to 10 June 2008 were screened for methicillin (meticillin)-resistant Staphylococcus aureus (MRSA) nasal colonization, and the isolates were tested for mupirocin susceptibility by using Etest. Mupirocin resistance (MR) was noted to occur in 3.4% of MRSA carriers, and high-level MR was noted to occur in 0.62% of carriers.

Objective: To describe the epidemiology of hospital-acquired infections (HAIs) in veterans with spinal cord injury and disorder (SCI&D)., Design: Retrospective medical record review., Setting: Midwestern Department of Veterans Affairs spinal cord injury center., Participants: A total of 226 patients with SCI&D hospitalized at least once during a 2-year period (October 1, 2001, through September 30, 2003)., Results: A total of 549 hospitalizations were included in the analysis (mean duration of hospitalization, 33.7 days); an HAI occurred during 182 (33.2%) of these hospitalizations. A total of 657 HAIs occurred during 18,517 patient-days in the hospital (incidence rate, 35.5 HAIs per 1,000 patient-days). Almost half of the 226 patients had at least 1 HAI; the mean number of HAIs among these patients was 6.0 HAIs per patient. The most common HAIs were urinary tract infection (164 [25.0%] of the 657 HAIs; incidence rate, 8.9 cases per 1,000 patient-days), bloodstream infection (111 [16.9%]; incidence rate, 6.0 cases per 1,000 patient-days), and bone and joint infection (103 [15.7%]; incidence rate, 5.6 cases per 1,000 patient-days). The most common culture isolates were gram-positive bacteria (1,082 [45.6%] of 2,307 isolates), including Staphylococcus aureus, and gram-negative bacteria (1,033 [43.6%] of isolates), including Pseudomonas aeruginosa. Multivariable regression demonstrated that predictors of HAI were longer length of hospital stay (P=.002), community-acquired infection (P=.007), and use of a urinary invasive device (P=.01) or respiratory invasive device (P=.04)., Conclusions: The overall incidence of HAIs in persons with SCI&D was higher than that reported for other populations, confirming the increased risk of HAI in persons with spinal cord injury. The increased risk associated with longer length of stay and with community-acquired infection suggests that strategies are needed to reduce the duration of hospitalization and to effectively treat community-acquired infection, to decrease infection rates. There is significant room for improvement in reducing the incidence of HAIs in this population.

Background: Community-acquired pneumonia (CAP) accounts for 1.5 million emergency department (ED) patient visits in the United States each year., Objectives: To derive an algorithm for the ED triage setting that facilitates rapid and accurate ordering of chest radiography (CXR) for CAP., Methods: The authors conducted an ED-based retrospective matched case-control study using 100 radiographic confirmed CAP cases and 100 radiographic confirmed influenzalike illness (ILI) controls. Sensitivities and specificities of characteristics assessed in the triage setting were measured to discriminate CAP from ILI. The authors then used classification tree analysis to derive an algorithm that maximizes sensitivity and specificity for detecting patients with CAP in the ED triage setting., Results: Temperature greater than 100.4 degrees F (likelihood ratio = 4.39, 95% confidence interval [CI] = 2.04 to 9.45), heart rate greater than 110 beats/minute (likelihood ratio = 3.59, 95% CI = 1.82 to 7.10), and pulse oximetry less than 96% (likelihood ratio = 2.36, 95% CI = 1.32 to 4.20) were the strongest predictors of CAP. However, no single characteristic was adequately sensitive and specific to accurately discriminate CAP from ILI. A three-step algorithm (using optimum cut points for elevated temperature, tachycardia, and hypoxemia on room air pulse oximetry) was derived that is 70.8% sensitive (95% CI = 60.7% to 79.7%) and 79.1% specific (95% CI = 69.3% to 86.9%)., Conclusions: No single characteristic adequately discriminates CAP from ILI, but a derived clinical algorithm may detect most radiographic confirmed CAP patients in the triage setting. Prospective assessment of this algorithm will be needed to determine its effects on the care of ED patients with suspected pneumonia.

Objectives: To determine the response rate of Clostridium difficile disease (CDD) to treatment with metronidazole and assess a scoring system to predict response to treatment with metronidazole when applied at the time of CDD diagnosis., Methods: Retrospective review of patients with CDD who received primary treatment with metronidazole. We defined success as diarrhea resolution within 6 days of therapy. A CDD score was defined prospectively using variables suggested to correlate with disease severity., Results: Among 102 evaluable patients, 72 had a successful response (70.6%). Twenty-one of the remaining 30 patients eventually responded to metronidazole, but required longer treatment, leaving 9 'true failures'. The mean CDD score was higher among true failures (2.89+/-1.4) than among all metronidazole responders (0.77+/-1.0) (p<.0001). The score was greater than 2 in 67% of true failures and 2 or less in 94% of metronidazole responders. Leukocytosis and abnormal CT scan findings were individual factors associated with a higher risk of metronidazole failure., Conclusions: Only 71% of CDD patients responded to metronidazole within 6 days, but the overall response rate was 91%. A CDD score greater than 2 was associated with metronidazole failure in 6 of 9 true failures. The CDD score will require prospective validation.

Background: Nosocomial infection may contribute to poor long-term consequences in persons who have spinal cord injuries and disorders (SCI&D)., Methods: This is a cohort study of individuals who had SCI&D and were hospitalized at least once during 2002. They were followed for 3 years to assess inpatient (IP) admissions, total IP length of stay (LOS), outpatient (OP) visits, and mortality. Count data models and a Cox proportional hazards model were used to assess the relationship between previous infection and subsequent IP and OP use and long-term mortality, respectively., Results: Of persons who had SCI&D, 59% had at least one nosocomial infection. Multivariable regression indicated that veterans who had SCI&D had more IP admissions (b = 0.405; P < .0001) and longer IP LOS (b = 0.843; P < .0001) if they had a previous infection; however, infection status was not a predictor of future OP visits. Survival time was lower (913.93 versus 1034.75 days, P = .004) in the infection group. Death rate was higher in the nosocomial infection group (30.11% versus 10.77%; P = .004), but the association did not achieve significance in the Cox proportional hazards model (P = .12)., Conclusions: Nosocomial infections have serious subsequent consequences that result in future hospitalization and shorter survival. Efforts to prevent nosocomial infections are needed to reduce long-term adverse effects in persons who have SCI&D.

Objective: To identify patients with a diagnosis of Clostridium difficile-associated disease (CDAD) in the ambulatory care setting and determine the relationship of symptom onset and diagnosis to prior hospitalization and exposure to antimicrobials., Design: Single-center, retrospective study., Methods: Medical records were reviewed for outpatients and hospitalized patients with a stool assay positive for C. difficile toxin A from January 1998 through March 2005. Patients with recurrent CDAD or residing in an extended-care facility were excluded. CDAD in patients who had been hospitalized in the 100 days prior to diagnosis was considered potentially hospital-associated., Results: Of the 84 patients who met the inclusion criteria, 75 (89%) received a diagnosis 1-60 days after hospital discharge (median, 12 days), and 71 (85%) received a diagnosis within 30 days after discharge. Of the 69 patients whose records contained information regarding time of symptom onset, 62 (90%) developed diarrhea within 30 days of a previous hospital discharge, including 7 patients with symptom onset prior to discharge and 9 with onset on the day of discharge. The median time from symptom onset to diagnosis was 6 days. Of 84 patients, 77 (92%) had received antimicrobials during a prior hospitalization, but 55 (65%) received antimicrobials both as inpatients and as outpatients., Conclusion: If all cases of CDAD diagnosed within 100 days of hospital discharge were assumed to be hospital-associated, 71 (85%) of 84 patients with CDAD were identified within 30 days, and 75 (89%) of 84 were identified by day 60. Continued outpatient antimicrobial exposure confounds determination of whether late-onset cases are community- or hospital-associated.

Purpose. Febrile neutropenia (FN) is a common, costly, and potentially fatal complication in oncology. While FN in the inpatient setting has been extensively studied, only one study has evaluated emergency department (ED) care for FN cancer patients. That study found that 96% of patients survived the complication. We evaluated clinical and economic outcomes for cancer patients with chemotherapy-associated FN treated in an ED. Methods. ED records for consecutive oncology patients with FN were reviewed for information on death, intensive care unit (ICU) use, blood cultures, and costs. Results. Forty-eight patients (n = 57 visits) were evaluated. Six patients died from FN (12%) and four received ICU care within 2 weeks and survived (8%). Blood cultures were positive for 37% of the ED visits. The median ED time was 3.3 hours. In 91% of visits, i.v. antibiotics were administered in the ED, ordered at a median of 1.7 hours from triage (interquartile range [IQR], 1.2-2.8 hours). All patients with death or ICU in 2 weeks and all but one patient with positive blood cultures received antibiotics. The median per patient ED costs were $1,455 (IQR, $1,300-$1,579)-42.4% for hospital/nursing, 23.5% for radiology, 20.8% for physician services, 10.9% for diagnostic tests, and 2.4% for antibiotics. Conclusions. Cancer patients with FN in this sample presenting to the ED frequently had no identified source of infection. One third of the patients had positive ED blood cultures and one fifth died or required ICU care within 2 weeks. Costs of ED care were similar to the cost of a single day of inpatient care. Disclosure of potential conflicts of interest is found at the end of this article.

Background: In 2001, a small-scale bioterrorism-related anthrax attack was perpetrated via the US mail. The optimal future response may require strategies different from those required in a large-scale attack., Methods: We conducted a cost-effectiveness analysis using Monte Carlo simulation during a 10-year time frame from a societal perspective to determine the optimal response strategy for a small-scale anthrax attack perpetrated against US Postal Service distribution centers in a large metropolitan area. Three strategies were compared: preattack vaccination of all US distribution center postal workers, postattack antibiotic therapy followed by vaccination of exposed personnel, and postattack antibiotic therapy without vaccination of exposed personnel. Outcome measures were costs, quality-adjusted life-years, and incremental cost-effectiveness. The probabilities for anthrax exposure and infection; vaccine and antibiotic benefits, risks, and costs; and associated clinical outcomes were derived from the medical literature and from bioterrorism experts., Results: Postattack antibiotic therapy and vaccination of exposed postal workers is the most cost-effective response compared with other strategies. The incremental cost-effectiveness is $59 558 per quality-adjusted life-year compared with postattack antibiotic therapy alone. Preattack vaccination of all distribution center workers is less effective and more costly than the other 2 strategies. Assuming complete adherence to preattack vaccination, the incremental cost-effectiveness compared with postattack antibiotic therapy alone is almost $2.6 million per quality-adjusted life-year., Conclusion: Despite uncertainties about a future anthrax attack and exposure risk, postattack antibiotic therapy and vaccination of exposed personnel seems to be the optimal response to an attack perpetrated through the US Postal Service.

Background: Corynebacterium species are recognized as uncommon agents of endocarditis, but little is known regarding species-specific risk factors and outcomes in Corynebacterium endocarditis., Methods: Case report and Medline search of English language journals for cases of Corynebacterium endocarditis. Inclusion criteria required that cases be identified as endocarditis, having persistent Corynebacterium bacteremia, murmurs described by the authors as identifying the affected valve, or vegetations found by echocardiography or in surgical or autopsy specimens. Cases also required patient-specific information on risk factors and outcomes (age, gender, prior prosthetic valve, other prior nosocomial risk factors (infected valve, involvement of native versus prosthetic valve, need for valve replacement, and death) to be included in the analysis. Publications of Corynebacterium endocarditis which reported aggregate data were excluded. Univariate analysis was conducted with chi-square and t-tests, as appropriate, with p = 0.05 considered significant., Results: 129 cases of Corynebacterium endocarditis involving nine species met inclusion criteria. Corynebacterium endocarditis typically infects the left heart of adult males and nearly one third of patients have underlying valvular disease. One quarter of patients required valve replacement and one half of patients died. Toxigenic C. diphtheriae is associated with pediatric infections (p < 0.001). Only C. amycolatum has a predilection for women (p = 0.024), while C. pseudodiphtheriticum infections are most frequent in men (p = 0.023). C. striatum, C. jeikeium and C. hemolyticum are associated with nosocomial risk factors (p < 0.001, 0.028, and 0.024, respectively). No species was found to have a predilection for any particular heart valve. C. pseudodiphtheriticum is associated with a previous prosthetic valve replacement (p = 0.004). C. jeikeium infections are more likely to require valve replacement (p = 0.026). Infections involving toxigenic C. diphtheriae and C. pseudodiphtheriticum are associated with decreased survival (p = 0.001 and 0.032, respectively)., Conclusion: We report the first analysis of species-specific risk factors and outcomes in Corynebacterium endocarditis. In addition to species-specific associations with age, gender, prior valvular diseases, and other nosocomial risk factors, we found differences in rates of need for valve replacement and death. This review highlights the seriousness of these infections, as up to 28% of patients required valve replacement and 43.5% died.

Although well-recognized animal pathogens, group C streptococci are relatively rare causes of human infection. The phenotypically small-colony group C 'Streptococcus milleri' are typically associated with suppurative disease of soft tissue and organs, including liver abscesses, while bacteraemia and endocarditis are distinctly less common. Herein, a case of 'S. milleri' causing both endocarditis and liver abscess in the same patient is reported.

Because penicillin agents are implicated in granulopoiesis inhibition, healthcare professionals frequently consider discontinuation of such therapy in patients with decreasing white blood cell counts. No systematic review to date has described piperacillin and the patient population at risk for this adverse drug reaction (ADR). This review sought to assess the occurrence of piperacillin-induced neutropenia, describe characteristics of affected patients and assess the reporting modalities that most accurately classify this ADR. Case reports, cohort studies and clinical trials identified by comprehensive searches of PubMed and the US FDA Adverse Event Reporting System (AERS) database were reviewed for patient demographics, duration and dose of piperacillin or piperacillin-tazobactam treatment and the occurrence of neutropenia. Causality assessments were performed. Six published case reports, three cohort studies, 178 clinical trials and two compilations of phase I-III trials were reviewed. Review of case reports was notable in that the duration of beta-lactam therapy prior to the noting of leukopenia always exceeded 15 days. No deaths were recorded in this group. Among 13,816 patients enrolled in non-neutropenic fever studies, the occurrence of piperacillin-induced neutropenia was rare: five patients (0.04%) developed neutropenia; none died. The demographics for this group were poorly documented. Through the AERS database, we identified 366 unique cases of piperacillin or piperacillin-tazobactam-induced haematological abnormalities, including neutropenia (n = 183, 50.0%), leukopenia, (n = 99, 27%), agranulocytosis (n = 58, 15.8%) and others. In 62 cases, patients received between 1 and 14 days of therapy (mean 7.7 + 4.1 days). Overall, there were 82 (22.4%) deaths. Reports of haematological ADRs among patients receiving piperacillin or piperacillin-tazobactam are rare. Report of neutropenia associated with piperacillin usage prior to 15 days of therapy is a novel finding that requires further evaluation. Current reporting methods poorly characterise patient groups at risk.

The prostate gland is a rare site of primary infection due to Cryptococcus neoformans; however, it may serve as a site of its sequestration after an occult or treated disseminated infection. Serum prostate specific antigen may correlate with the severity of prostatic inflammation, but its role as a diagnostic and prognostic marker is unclear. We report the first case of primary cryptococcal prostatitis in a renal transplant recipient. The diagnosis was established based on asymmetrically enlarged prostate gland, markedly elevated serum PSA levels, cryptococcal fungemia, an ultrasound-guided prostatic biopsy that demonstrated cryptococcal fungal elements and growth of C. neoformans on culture. The patient was successfully treated with a prolonged course of fluconazole and remained disease-free for more than 28 months of follow-up. In addition, we present a review of the published literature since 1946 and discuss possible correlation with PSA levels.

Background: Blood culture (BCX) use is often sub-optimal, and is a user-dependent diagnostic test. Little is known about physician training and BCX-related knowledge. We sought to assess variations in caregiver BCX-related knowledge, and their relation to medical training., Methods: We developed and piloted a self-administered BCX-related knowledge survey instrument. Expert opinion, literature review, focus groups, and mini-pilots reduced > 100 questions in multiple formats to a final questionnaire with 15 scored content items and 4 covariate identifiers. This questionnaire was used in a cross-sectional survey of physicians, fellows, residents and medical students at a large urban public teaching hospital. The responses were stratified by years/level of training, type of specialty training, self-reported practical and theoretical BCX-related instruction. Summary scores were derived from participant responses compared to a 95% consensus opinion of infectious diseases specialists that matched an evidence based reference standard., Results: There were 291 respondents (Attendings = 72, Post-Graduate Year (PGY) = 3 = 84, PGY2 = 42, PGY1 = 41, medical students = 52). Mean scores differed by training level (Attending = 85.0, PGY3 = 81.1, PGY2 = 78.4, PGY1 = 75.4, students = 67.7) [p < or = 0.001], and training type (Infectious Diseases = 96.1, Medicine = 81.7, Emergency Medicine = 79.6, Surgery = 78.5, Family Practice = 76.5, Obstetrics-Gynecology = 74.4, Pediatrics = 74.0) [p < or = 0.001]. Higher summary scores were associated with self-reported theoretical [p < or = 0.001] and practical [p = 0.001] BCX-related training. Linear regression showed level and type of training accounted for most of the score variation., Conclusion: Higher mean scores were associated with advancing level of training and greater subject-related training. Notably, house staff and medical students, who are most likely to order and/or obtain BCXs, lack key BCX-related knowledge. Targeted education may improve utilization of this important diagnostic tool.

Objectives: Most acute respiratory infections (ARIs) are viral and do not warrant antibiotic therapy. Studies to date have not examined trends in antibiotic use in ARIs in populations with disabilities, thus we assessed antibiotic prescribing for veterans with spinal cord injury and disorder (SCI and D) with outpatient ARI visits., Patients and Methods: Retrospective study using Department of Veterans Affairs (VA) administrative and pharmacy datasets (1 October 1998-30 September 2001; fiscal years 1999-2001) to assess antibiotic prescribing for upper respiratory infection (URI), lower respiratory infection (LRI), and pneumonia in veterans with SCI and D., Results: There were 5713 ARI visits; 50% received new antibiotic prescriptions. URI and LRI visits were 2.3 times and almost 4 times (P < 0.0001), respectively, more likely to have antibiotics prescribed than pneumonia visits. The majority of URI visits with antibiotic prescriptions had a diagnosis of the common cold or URI not otherwise specified (78%). Acute bronchitis without exacerbation was associated with 95% of LRI visits that received antibiotics. Broad-spectrum antibiotic use increased over time (1999, 46%; 2001, 62%; P < 0.0001)., Conclusions: Although rates of antibiotic prescribing remained stable, prescriptions for broad-spectrum antibiotics increased. Most prescriptions were for indications for which antibiotic use is generally not recommended. Since patients with SCI and D are susceptible to multiple complications, providers may be more concerned with ensuring that any infection is treated, rather than the potential for overuse and resistance. Future efforts should focus on defining benefits of antibiotic use for ARIs in those with disabilities, predictors of prescribing, and interventions to prevent injudicious use of antibiotics.

Context: In 1998, a multidisciplinary team of investigators initiated RADAR (Research on Adverse Drug events And Reports), a clinically based postmarketing surveillance program that systematically investigates and disseminates information describing serious and previously unrecognized adverse drug and device reactions (ADRs)., Objective: To describe the structure, operations, and preliminary findings from the RADAR project and related dissemination efforts by pharmaceutical suppliers and the US Food and Drug Administration (FDA)., Design: After identifying a serious and unexpected clinical event suitable for further investigation, RADAR collaborators postulated clinical hypotheses and derived case series and incidence estimates from physician queries, published and unpublished clinical trials, published case reports, FDA databases, and manufacturer sales figures., Results: RADAR investigators identified 16 types of serious ADRs among 1699 patients, of whom 169 (10%) died as a result of the reaction. Initial cases were identified by 7 RADAR investigators, 4 collaborating physicians, 2 attorneys, and by reviewing 3 published reports. Additional sources included queries of occupational health programs and medical directors of interventional cardiology laboratories (3 types of ADRs), published manuscripts and clinical trials (11 types of ADRs), review of medical records at a RADAR site (2 types of ADRs), unpublished clinical trial reports (3 types of ADRs), and reports from attorneys, family members, or patients (4 types of ADRs). Incidence estimates, ranging from 0.4% to 33%, were derived from 5 clinical trial reports, 2 physician queries, and 2 observational databases. Laboratory support for hypotheses included identification of 3 neutralizing antibodies and 3 histopathological findings. ADR reports were disseminated as 8 revised package inserts, 7 "dear doctor" letters, and 9 peer-reviewed articles., Conclusion: A new, clinically based, hypothesis-driven approach to postmarketing surveillance may supplement existing regulatory surveillance systems and improve patient safety.

Objective: To report 2 cases of multidrug-resistant (MDR) Pseudomonas aeruginosa meningitis and ventriculo-peritoneal shunt (VPS) infection successfully sterilized with intrathecal colistin 10 mg/day after development of nephrotoxicity associated with intravenous administration., Case Summaries: Case 1. A 69-year-old African American woman with a history of subarachnoid hemorrhage and hydrocephalus requiring VPS placement was admitted with VPS infection and meningitis. Cerebrospinal fluid (CSF) cultures revealed MDR P. aeruginosa susceptible only to colistin. Intravenous colistin was initiated but rapidly discontinued due to development of renal dysfunction. Intravenous colistin was the probable cause of the adverse effect. Intrathecal colistin was initiated via an externalized VPS, with subsequent improvement in white blood cell counts in the CSF. Follow-up CSF cultures remained sterile and renal function returned to baseline. Case 2. A 69-year-old white woman with a history of subarachnoid hemorrhage, hydrocephalus, and VPS was transferred from an extended-care facility for management of a VPS infection. CSF cultures revealed MDR P. aeruginosa susceptible only to colistin. Intravenous colistin was initiated but subsequently discontinued due to worsening renal function that, as with the first case, probably correlated with colistin administration and persisted despite dose adjustment. Therapy was changed to intrathecal administration, with subsequent normalization of her CSF white blood cell counts and sterilization of cultures., Discussion: The limited availability of antibiotics for treatment of highly resistant or MDR gram-negative organisms has prompted clinicians to reconsider the use of older drugs. Prior reports have suggested that intravenous colistin is a potential alternative for treating highly resistant gram-negative central nervous system infections, specifically Acinetobacter, but its use is limited by nephrotoxicity. Our experience suggests that intrathecal colistin is a potentially curative intervention for the treatment of severe MDR P. aeruginosa meningitis and VPS infections in patients in whom intravenous colistin is not an option., Conclusions: Intrathecal use of colistin is a potentially safe, effective, and viable treatment option for MDR P. aeruginosa central nervous system infections when intravenous administration is not feasible.

Objective: To determine whether documentation of a causative organism for community-acquired pneumonia (CAP) is associated with outcomes, including mortality and length of stay (LOS), in hospitalized veterans with spinal cord injuries and disorders (SCI&D)., Design: Retrospective cohort study., Setting: Patients with SCI&D admitted with CAP to any Veterans Affairs medical center between September 1998 and October 2000., Participants: Hospital administrative data on 260 patients with SCI&D and a CAP diagnosis., Interventions: Not applicable., Main Outcomes Measures: All-cause, 30-day mortality and hospital LOS., Results: An organism was documented by International Classification of Diseases, 9th Revision , discharge codes in 24% of cases. Streptococcus pneumoniae and Pseudomonas aeruginosa accounted for 32% and 21%, respectively, of the identified bacterial pathogens. The overall mortality rate was 8.5%. No significant association was found between etiologic diagnosis of CAP and 30-day mortality. Lower mortality was associated with treatment at a designated SCI center (relative risk=.35; confidence interval, .12-.99). Pathogen-based CAP diagnosis was significantly associated with longer LOS (adjusted r 2 =.023, P =.024)., Conclusions: There was no association between etiologic diagnosis of CAP and 30-day mortality among people with SCI&D. Documentation of CAP etiology was associated with the variance in LOS. Pneumococcal vaccination and antibiotic therapy with antipseudomonal activity may be particularly prudent in these patients given the high frequency of these pathogens among SCI&D patients with CAP.

Background: While prior studies have shown that public and private hospitals differ in their rates of suspicion and isolation of patients who are at risk for tuberculosis (TB), no study has investigated whether this variation is due to differences in the impact of patient case-mix on hospitals or to variations attributable to specific hospital practice patterns., Objective: To investigate patient-level and hospital-level factors associated with delays in TB suspicion and isolation among inpatients with pulmonary TB disease., Design: Retrospective cohort study of patients hospitalized with culture-positive pulmonary TB during 1996 to 1999., Setting: Patients with culture-proven pulmonary TB treated at three public hospitals (765 patients) and seven not-for-profit private hospitals (172 patients) in Chicago, Los Angeles, and southern Florida that provided care for five or more patients with TB per year during the study period., Measurements: Two-day rates (within 48 h from admission) of acid-fast bacilli (AFB) smear orders and 1-day rates (within 24 h from admission) of TB isolation., Results: Two-day rates of ordering AFB smears were > 80% at three public and two private hospitals vs 65 to 75% at five private hospitals. One-day rates of TB isolation at the three public hospitals were 64%, 79%, and 86%, respectively, vs 39 to 58% at the seven private hospitals. Delays of > 2 days in ordering AFB smears were associated with patient-level factors: absence of cough (adjusted odds ratio [AOR], 6.02; 95% confidence interval [CI], 3.82 to 9.52), cavitary lung lesion (AOR, 5.17; 95% CI, 1.98 to 13.50), night sweats (AOR, 3.38; 95% CI, 1.90 to 5.99), chills (AOR, 1.70; 95% CI, 1.01 to 2.88), and female gender (AOR, 1.66; 95% CI, 1.06 to 2.60). Delays of > 1 day in ordering pulmonary isolation were associated with patient-level factors: absence of cough (AOR, 3.40; 95% CI, 2.31 to 5.03), cavitary lung lesion (AOR, 2.66; 95% CI, 1.57 to 4.50), night sweats (AOR, 1.98; 95% CI, 1.35 to 2.92), and history of noninjecting drug use (AOR, 1.86; 95% CI, 1.16 to 2.99) and one hospital-level factor: receiving care at a nonpublic hospital. Even after adjustment for patient-level factors, TB patients at private hospitals were half as likely as those at public hospitals to be placed in pulmonary isolation (AOR, 0.47; 95% CI, 0.30 to 0.72), while odds of suspecting TB in these same patients were similar at both hospitals., Conclusion: Private hospitals should order TB isolation for all patients for whom AFB smears are ordered, a policy that has been instituted previously at public hospitals in our study.

Study Design: Retrospective case series., Objectives: Respiratory disorders are the leading cause of death in persons with spinal cord injury (SCI), but the epidemiology and medical management of pneumonia in persons with chronic SCI is not well characterized. We describe the clinical presentation of persons with SCI with community-acquired pneumonia (CAP), characterize its management and compare practice to recommendations for CAP in the general population., Setting: Three United States Veterans Affairs Medical Centers with specialized SCI services., Methods: Chart abstraction was performed for all persons with chronic SCI seen at participating centers for treatment of CAP during a 2-year period. Collected data included presenting signs and symptoms, laboratory and imaging results, initial antibiotic therapy, secretion mobilization techniques, in-patient vs outpatient management, length of stay, and mortality., Results: In all, 41 persons with SCI received treatment for CAP during the study period. A total of 32 (78.0%) patients were admitted for treatment; two (4.8%) required intubation and mechanical ventilation. Initial antibiotic coverage met guideline recommendations for only half of inpatients and infrequently provided adequate antipseudomonal coverage. Microbiologic testing was performed on 26 cases (63.4%) and demonstrated a specific pathogen in only five cases (12.2% of total). Three cases (7.3%) died during treatment for CAP, and 16 (42.1%) of 38 CAP survivors died within a median follow-up of 3 years., Conclusion: The majority of chronic SCI patients who present to specialized SCI centers with CAP are admitted for treatment. Short-term mortality is comparable to CAP in the general population.

Age-related variations in care have been identified for HIV-associated Pneumocystis carinii pneumonia (PCP) in both the 1980s and 1990s. We evaluated if age-related variations affected all aspects of HIV-specific and non-HIV-specific care for HIV-infected individuals with PCP or community-acquired pneumonia (CAP), or whether age-related variations were primarily limited to HIV-specific aspects of care. Subjects were HIV-infected persons with PCP (n = 1855) or CAP (n = 1415) hospitalized in 8 cities from 1995 to 1997. Nine percent of our study patients had received protease inhibitors and 39% had received any type of antiretroviral therapy prior to hospitalization. Data were abstracted from medical records and included severity of illness, HIV-specific aspects of care (initiation of PCP medications), general measures of care [initiation of CAP medications, intubation, and intensive care units (ICU)], and inpatient mortality. Compared to younger patients, pneumonia patients 50 years of age or older were significantly more likely to: be severely ill (PCP, 20.4% vs. 10.4%; CAP, 27.5% vs. 14.9%; each p = 0.001), receive ICU care (PCP, 22.0% vs. 12.8%, p = 0.002; CAP: 15.1% vs. 9.4%; p = 0.02), and be intubated (PCP, 14.6% vs. 8.4%, p = 0.01; CAP, 9.9% vs. 5.6%, p = 0.03). Compared to younger patients, older patients (>/=50 years) had similar rates of timely medications for CAP (48.5% vs. 50.8%) but had lower rates of receiving anti-PCP medications (85.8% vs. 92.9%, p = 0.002). Differences by age in timely initiation of PCP medications, ICU use, and intubation were limited to the nonseverely ill patients. Older hospitalized patients were more likely to die (PCP, 18.3% vs. 10.4%; CAP, 13.4% vs. 8.5%; each p < 0.05). After adjustment for disease severity and timeliness of antibiotic use, mortality rates were similar for both age groups. Physicians should develop strategies that increase awareness of the possibility of HIV infection in older individuals.

In the late 1980s, Medicaid-insured human immunodeficiency virus (HIV)-infected patients with Pneumocystis carinii pneumonia (PCP) were 40% less likely to undergo diagnostic bronchoscopy and 75% more likely to die than were privately insured patients, whereas rates of use of other, less resource-intensive aspects of PCP care were similar. We reviewed 1395 medical records at 59 hospitals in 6 cities for the period 1995-1997 to examine the impact of insurance status on PCP-related care. Medicaid patients were only one-half as likely to undergo diagnostic bronchoscopy as were privately insured patients, yet we found no evidence that mortality was greater among patients who received empirical treatment. The bronchoscopy rates were primarily related to patients' personal insurance status. A weaker hospital-level effect was seen that was related to hospitals' Medicaid/private insurance case mix ratios. The situation has evolved from one in which Medicaid coverage was associated with underuse of bronchoscopy and poorer survival among empirically treated persons with HIV-related PCP to one in which empirical therapy is effective in treating this disease and expensive diagnostic procedures may be overused for privately insured patients.