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Objective: Among patients with a history of ESBL infection, uncertainty remains regarding whether all of these patients require ESBL-targeted therapy when presenting with a subsequent infection. We sought to determine the risks associated with a subsequent ESBL infection to help inform empiric antibiotic decisions., Methods: A retrospective cohort study of adult patients with positive index culture for Escherichia coli or Klebsiella pneumoniae (EC/KP) receiving medical care during 2017 was conducted. Risk assessments were performed to identify factors associated with subsequent infection caused by ESBL-producing EC/KP., Results: In total, 200 patients were included in the cohort, 100 with ESBL-producing EC/KP and 100 with ESBL-negative EC/KP. Of 100 patients (50%) who developed a subsequent infection, 22 infections were ESBL-producing EC/KP, 43 were other bacteria, and 35 had no or negative cultures. Subsequent infection caused by ESBL-producing EC/KP only occurred when the index culture was also ESBL-producing (22 vs 0). Among those with ESBL-producing index culture, the incidences of subsequent infection caused by ESBL-producing EC/KP versus other bacterial subsequent infection were similar (22 vs 18; P = .428). Factors associated with subsequent infection caused by ESBL-producing EC/KP include history of ESBL-producing index culture, time ≤180 days between index culture and subsequent infection, male sex, and Charlson comorbidity index score >3., Conclusions: History of ESBL-producing EC/KP culture is associated with subsequent infection caused by ESBL-producing EC/KP, particularly within 180 days after the historical culture. Among patients presenting with infection and a history of ESBL-producing EC/KP, other factors should be considered in making empiric antibiotic decisions, and ESBL-targeted therapy may not always be warranted., Competing Interests: All authors report no conflicts of interest relevant to this article., (© The Author(s) 2023.)

Objective: To evaluate the clinical impact of the BioFire FilmArray Pneumonia Panel (PNA panel) in critically ill patients., Design: Single-center, preintervention and postintervention retrospective cohort study., Setting: Tertiary-care academic medical center., Patients: Adult ICU patients., Methods: Patients with quantitative bacterial cultures obtained by bronchoalveolar lavage or tracheal aspirate either before (January-March 2021, preintervention period) or after (January-March 2022, postintervention period) implementation of the PNA panel were randomly screened until 25 patients per study month (75 in each cohort) who met the study criteria were included. Antibiotic use from the day of culture collection through day 5 was compared., Results: The primary outcome of median time to first antibiotic change based on microbiologic data was 50 hours before the intervention versus 21 hours after the intervention ( P = .0006). Also, 56 postintervention regimens (75%) were eligible for change based on PNA panel results; actual change occurred in 30 regimens (54%). Median antibiotic days of therapy (DOTs) were 8 before the intervention versus 6 after the intervention ( P = .07). For the patients with antibiotic changes made based on PNA panel results, the median time to first antibiotic change was 10 hours. For patients who were initially on inadequate therapy, time to adequate therapy was 67 hours before the intervention versus 37 hours after the intervention ( P = .27)., Conclusions: The PNA panel was associated with decreased time to first antibiotic change and fewer antibiotic DOTs. Its impact may have been larger if a higher percentage of potential antibiotic changes had been implemented. The PNA panel is a promising tool to enhance antibiotic stewardship., (© The Author(s) 2023.)

Professional societies serve many functions that benefit constituents; however, few professional societies have undertaken the development and dissemination of formal, national curricula to train the future workforce while simultaneously addressing significant healthcare needs. The Infectious Diseases Society of America (IDSA) has developed 2 curricula for the specific purpose of training the next generation of clinicians to ensure the future infectious diseases (ID) workforce is optimally trained to lead antimicrobial stewardship programs and equipped to meet the challenges of multidrug resistance, patient safety, and healthcare quality improvement. A core curriculum was developed to provide a foundation in antimicrobial stewardship for all ID fellows, regardless of career path. An advanced curriculum was developed for ID fellows specifically pursuing a career in antimicrobial stewardship. Both curricula will be broadly available in the summer of 2021 through the IDSA website., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

There have been tremendous advances in methodologies available for detection and identification of organisms causing infections. Providers can now obtain identification results and antimicrobial susceptibility results in a shorter period of time. However, declining health care resources highlight the importance of selecting the right test at the right time to maximize diagnostic benefits. Therefore, the role of the antimicrobial stewardship team in the clinical microbiology laboratory has expanded to include diagnostic stewardship and provision of guidance on test selection for diagnosis and management of infection. This review focuses on the experience of our group in collaborative stewardship, emphasizing successes and challenges., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2019 Elsevier Inc. All rights reserved.)

We describe the proportion of pharmacist representation among current and corresponding prior editions of Infectious Diseases Society of America (IDSA) clinical practice guidelines (CPGs). Pharmacist representation was 13% and 21% in previous and current editions, respectively, increasing significantly since 2011. We advocate for continued collaborations between IDSA and pharmacy organizations to enhance multidisciplinary representation in CPGs.

A needs assessment survey of infectious diseases (ID) training program directors identified gaps in educational resources for training and evaluating ID fellows in antimicrobial stewardship. An Infectious Diseases Society of America-sponsored core curriculum was developed to address that need.

Evidence-based guidelines for implementation and measurement of antibiotic stewardship interventions in inpatient populations including long-term care were prepared by a multidisciplinary expert panel of the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. The panel included clinicians and investigators representing internal medicine, emergency medicine, microbiology, critical care, surgery, epidemiology, pharmacy, and adult and pediatric infectious diseases specialties. These recommendations address the best approaches for antibiotic stewardship programs to influence the optimal use of antibiotics., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Evidence-based guidelines for implementation and measurement of antibiotic stewardship interventions in inpatient populations including long-term care were prepared by a multidisciplinary expert panel of the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. The panel included clinicians and investigators representing internal medicine, emergency medicine, microbiology, critical care, surgery, epidemiology, pharmacy, and adult and pediatric infectious diseases specialties. These recommendations address the best approaches for antibiotic stewardship programs to influence the optimal use of antibiotics., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Background: The optimal therapy for critically ill patients with Clostridium difficile infection (CDI) is not known. We aimed to evaluate mortality among critically ill patients with CDI who received oral vancomycin (monotherapy) vs oral vancomycin with intravenous (IV) metronidazole (combination therapy)., Methods: A single-center, retrospective, observational, comparative study was performed. Patients with a positive C. difficile assay who received oral vancomycin while bedded in an intensive care unit (ICU) between June 2007 and September 2012 were evaluated. Patients meeting ≥3 of the following criteria were included: albumin <2.5 g/dL, heart rate >90 bpm, mean arterial pressure <60 mmHg, white blood cell count ≥15 000 cells/mL, age >60 years, serum creatinine ≥1.5 times baseline, or temperature ≥100.4°F. Patients in the combination therapy group received IV metronidazole within 48 hours after initiating vancomycin. Patients <18 years or with unrelated gastrointestinal disease were excluded. The primary outcome was in-hospital mortality. Patients were matched using Acute Physiology and Chronic Health Evaluation II scores., Results: Eighty-eight patients were included, 44 in each group. Patient characteristics were similar although more patients in the combination group had renal disease. Mortality was 36.4% and 15.9% in the monotherapy and combination therapy groups, respectively (P = .03). Secondary outcomes of clinical success, length of stay, and length of ICU stay did not differ between groups., Conclusions: Our data are supportive of the use of combination therapy with oral vancomycin and IV metronidazole in critically ill patients with CDI. However, prospective, randomized studies are required to define optimal treatment regimens in this limited population of CDI patients., (© 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.)

Antibiotic stewardship education for health care providers provides a foundation of knowledge and an environment that facilitates and supports optimal antibiotic prescribing. There is a need to extend this education to medical students and health care trainees. Education using passive techniques is modestly effective for increasing prescriber knowledge, whereas education using active techniques is more effective for changing prescribing behavior. Such education has been shown to enhance other antibiotic stewardship interventions. In this review, the need and suggested audience for antibiotic stewardship education are highlighted, and effective education techniques are recommended for increasing knowledge of antibiotics and improving their use., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Antibiotic selection is challenging in patients with severe β-lactam allergy due to declining reliability of alternate antibiotics. Organisms isolated from these patients may exhibit unique resistance phenotypes. The objective of this study was to determine which alternate antibiotics or combinations provide adequate empirical therapy for patients with β-lactam allergy who develop Gram-negative infections at our institution. We further sought to determine the effects of risk factors for drug resistance on empirical adequacy. A retrospective analysis was conducted for adult patients hospitalized from September 2009 to May 2010 who had a severe β-lactam allergy and a urine, blood, or respiratory culture positive for a Gram-negative organism and who met predefined criteria for infection. Patient characteristics, culture and susceptibility data, and predefined risk factors for antibiotic resistance were collected. Adequacies of β-lactam and alternate antibiotics were compared for all infections and selected subsets. The primary outcome was adequacy of each alternate antibiotic or combination for all infections. One hundred sixteen infections (40 pneumonias, 67 urinary tract infections, and 9 bacteremias) were identified. Single alternate agents were adequate less frequently than β-lactams and combination regimens. Only in cases without risk factors for resistance did single-agent regimens demonstrate acceptable adequacy rates; each factor conferred a doubling of risk for resistance. Resistance risk factors should be considered in selecting empirical antibiotics for Gram-negative pathogens in patients unable to take β-lactams due to severe allergy.

Objective: To describe a case of BK virus encephalitis with attempted direct antiviral therapy, review the reported cases of BK virus in the central nervous system, and report the novel use of intravenous cimetidine in place of oral probenecid to minimize the toxicities of intravenous cidofovir., Case Summary: A 36-year-old male with acute myelomonocytic leukemia and subsequent myelodysplastic syndrome underwent allogeneic hematopoietic stem cell transplant. His course was complicated by severe graft-versus-host disease involving his skin and gastrointestinal tract. Five weeks after transplantation, he developed fever and confusion. Magnetic resonance imaging was suggestive of limbic encephalitis and cerebrospinal fluid tested positive for BK virus. Therapy with intravenous cidofovir was thought to be indicated. Although probenecid is commonly used to minimize the toxicities of cidofovir, the patient's severe graft-versus-host disease raised concerns about absorption of oral medications. Based on animal models and pharmacokinetic data, intravenous cimetidine was used in place of oral probenecid. Despite these therapies, the patient's mental status did not improve. He developed progressive organ system failure, and care was ultimately withdrawn., Discussion: BK virus is increasingly described as a cause of encephalitis. The majority of reported cases have occurred in immunocompromised patients and have generally had a poor outcome. This case describes attempted antiviral therapy using cidofovir, the antiviral agent used most frequently in other syndromes due to BK virus. Intravenous cimetidine is a novel modality used to minimize ocular and renal toxicities frequently seen with cidofovir, and we believe this warrants further investigation., Conclusions: BK virus may be a cause of encephalitis in immunocompromised hosts, and cidofovir represents a possible treatment option. Intravenous cimetidine can be considered to minimize toxicities associated with cidofovir use in patients unable to tolerate or absorb oral probenecid.

Time-to-positivity (TTP) is defined as the length of time from the beginning of culture incubation to the detection of bacterial growth by an automated system. The objective of this study was to assess the clinical and microbiological implications of TTP among patients with Gram-negative bacilli (GNB) bacteremia. This was a prospective, single-center, observational study. Patients aged 18 years or older with one or more blood cultures growing GNB were included and followed until hospital discharge or death. Patients were excluded if they were without symptoms of infection, if they had polymicrobial culture, or if the culture was positive with an obligate anaerobe. A multivariate logistic regression analysis was performed to determine the predictors of in-hospital mortality, including TTP (primary endpoint), demographics, disease severity, comorbidities, pathogen type, source of infection, time to symptom resolution, hospital/intensive care unit (ICU) length of stay, adequacy of empiric antibiotics, and presence of an extended-spectrum beta-lactamase (ESBL)-producing bacteria. One hundred consecutive patients with GNB bacteremia were enrolled. TTP was an independent predictor of mortality; for every hour that TTP was shorter, the risk of mortality increased by 10% [odds ratio (OR) 1.10, 95% confidence interval (CI) 1.00-1.21, p = 0.049]. Other predictors of mortality included severity of illness, ESBL-producing GNB, and ICU admission within 24 h before culture. Mortality was highest among patients with inadequate empiric therapy (56% vs. 14%, p < 0.001) and TTP <11 h (23.1% vs. 8.3%, p = 0.18). Lactose-fermenting GNB had a shorter mean TTP than non-lactose fermenters (11.4 vs. 17.9 h, p = 0.001). Among patients with bacteremia due to GNB, TTP values are inversely associated with mortality risk.

By controlling and changing how antimicrobial agents are selected and administered, antimicrobial stewardship programs (ASPs) aim to prevent or slow the emergence of antimicrobial resistance; optimize the selection, dosing, and duration of antimicrobial therapy; reduce the incidence of drug-related adverse events; and lower rates of morbidity and mortality, length of hospitalization, and costs. There is an abundant and growing body of evidence demonstrating that ASPs change the quantity and quality of antimicrobial prescriptions; however, measuring whether, when, and how ASPs improve patient outcomes and change patterns of antimicrobial resistance--which is the ultimate goals of ASPs--has been difficult, but the totality of evidence indicates that ASPs are capable of achieving these goals. In this article, we review the existing data on ASPs and their effects on patient care and antimicrobial resistance, as well as strategies for establishing ASPs in different types of hospitals.

Antibiotic stewardship aims to improve patient care and reduce unwanted consequences of antimicrobial overuse or misuse, including lowered efficacy, emergence of antimicrobial resistance, development of secondary infections, adverse drug reactions, increased length of hospital stay, and additional healthcare costs. Recent guidelines make specific recommendations for the development of institutional programs to enhance antimicrobial stewardship. Optimally, such programs should be comprehensive, multidisciplinary, supported by hospital and medical staff leadership, and should employ evidence-based strategies that best fit local needs and resources. An infectious diseases physician and clinical pharmacist with infectious diseases training are recommended as core members of the multidisciplinary team, although a hospitalist with interest (and perhaps additional training) in antimicrobial therapy may be able to fill the void. Program directors and core members should be compensated for their time. Principal proactive strategies--with evidence supporting their consideration--include prospective audits, with intervention and feedback, formulary restriction, and preauthorization. Other strategies include persistent one-on-one education, guidelines adapted to local needs, and informatics to support clinical decision making. Intervention goals are to prevent unnecessary antimicrobial starts, to streamline or de-escalate therapy early in its course, and to convert from parenteral to oral therapy, optimize dosing, and ensure the appropriate length of therapy. Most community hospitals, if sufficiently resourced, should be able to implement a successful antimicrobial stewardship program. Evidence suggests that good antimicrobial stewardship can lead to less overall and inappropriate antimicrobial use, lower drug-related costs, reductions in Clostridium difficile-associated disease, and, in some studies, less emergence of antimicrobial resistance., (Copyright © 2011 Society of Hospital Medicine.)

The role of corticosteroid therapy in addition to anti-tuberculous agents in the treatment of hepatic tuberculosis is unclear. We describe a 54-y-old female with hepatic tuberculosis and worsening hepatitis after initiation of anti-tuberculosis therapy. She experienced considerable clinical improvement and ultimately a complete recovery upon the receipt of adjunctive corticosteroids.

Background: Rickettsia parkeri rickettsiosis, a recently identified spotted fever transmitted by the Gulf Coast tick (Amblyomma maculatum), was first described in 2004. We summarize the clinical and epidemiological features of 12 patients in the United States with confirmed or probable disease attributable to R. parkeri and comment on distinctions between R. parkeri rickettsiosis and other United States rickettsioses., Methods: Clinical specimens from patients in the United States who reside within the range of A. maculatum for whom an eschar or vesicular rash was described were evaluated by > or =1 laboratory assays at the Centers for Disease Control and Prevention (Atlanta, GA) to identify probable or confirmed infection with R. parkeri., Results: During 1998-2007, clinical samples from 12 patients with illnesses epidemiologically and clinically compatible with R. parkeri rickettsiosis were submitted for diagnostic evaluation. Using indirect immunofluorescence antibody assays, immunohistochemistry, polymerase chain reaction assays, and cell culture isolation, we identified 6 confirmed and 6 probable cases of infection with R. parkeri. The aggregate clinical characteristics of these patients revealed a disease similar to but less severe than classically described Rocky Mountain spotted fever., Conclusions: Closer attention to the distinct clinical features of the various spotted fever syndromes that exist in the United States and other countries of the Western hemisphere, coupled with more frequent use of specific confirmatory assays, may unveil several unique diseases that have been identified collectively as Rocky Mountain spotted fever during the past century. Accurate assessments of these distinct infections will ultimately provide a more valid description of the currently recognized distribution, incidence, and case-fatality rate of Rocky Mountain spotted fever.

Objective: To determine whether a multi-interventional program can limit increases in prescription drug expenditures while maintaining utilization of needed medications., Study Design: Quasi-experimental, pre-post design., Methods: The program included formulary changes, quantity limits, and mandatory pill splitting for select drugs implemented in phases. We assessed the short-term effects of each intervention by comparing class-specific drug spending and generic medication use before and after benefit changes. Long-term effects were determined by comparing overall spending with projected spending estimates, and by examining changes in the planwide use of generic medications over time. Effects on medication utilization were assessed by examining members' use of selected classes of chronic medications before and after the policy changes., Results: Over 3 years, the plan and members saved $6.6 million attributed to the interventions. Most of the savings were due to the reclassification of select brand-name drugs to nonpreferred status (estimated annual savings, $941,000), followed by the removal of nonsedating antihistamines from the formulary (annual savings, $565,000), and the introduction of pill splitting (annual savings, $342,000). Limiting quantities of select medications had the smallest impact (annual savings, $135,000). Members' use of generic medications steadily increased from 40% to 57%. Although 17.5% of members stopped using at least 1 class of selected medications, members' total use of chronic medications remained constant., Conclusions: A combination of interventions can successfully manage prescription drug spending while preserving utilization of chronic medications. Additional studies are needed to determine the effect of these cost-control interventions on other health outcomes.

Background: While current guidelines recommend consideration of local microbiologic data when selecting empiric treatment for hospital-acquired pneumonia (HAP), few specifics of how to do this have been offered., Methods: We conducted a retrospective analysis of HAP pathogens in 111 consecutive patients who acquired HAP during July to December 2004 and had a corresponding positive culture finding for a bacterial pathogen. These data were used to develop institution-specific guidelines., Results: The most common bacteria identified were Staphylococcus aureus, Acinetobacter baumannii, and Pseudomonas aeruginosa, which were associated with 38%, 25%, and 19% of pneumonias, respectively. Susceptibility of Gram-negative bacteria to piperacillin-tazobactam and cefepime was 80% and 81%, respectively. The isolation of organisms resistant to piperacillin-tazobactam or cefepime was significantly more frequent in patients who had been hospitalized > or = 10 days. Of Gram-negative isolates resistant to piperacillin-tazobactam or cefepime, ciprofloxacin was active against < 10%, while amikacin was active against > 80%. New treatment guidelines were developed that divided the American Thoracic Society/Infectious Diseases Society of America "late onset/risk of multidrug-resistant pathogens" group of patients into two subcategories: "early-late" pneumonias (< 10 days of hospitalization) and "late-late" pneumonias (> or = 10 days of hospitalization). Guideline-directed treatment regimens would be predicted to provide adequate initial therapy for > 90% of late-onset pneumonias at our institution., Conclusions: Current guidelines suggest adding either an aminoglycoside or a fluoroquinolone to beta-lactam therapy for empiric Gram-negative coverage. However, in our institution, adding ciprofloxacin would not appreciably enhance the likelihood of providing initial appropriate antibiotic coverage. This underscores the importance of employing a systematic analysis of local data when developing treatment guidelines.

Tickborne rickettsial diseases (TBRD) continue to cause severe illness and death in otherwise healthy adults and children, despite the availability of low cost, effective antimicrobial therapy. The greatest challenge to clinicians is the difficult diagnostic dilemma posed by these infections early in their clinical course, when antibiotic therapy is most effective. Early signs and symptoms of these illnesses are notoriously nonspecific or mimic benign viral illnesses, making diagnosis difficult. In October 2004, CDC's Viral and Rickettsial Zoonoses Branch, in consultation with 11 clinical and academic specialists of Rocky Mountain spotted fever, human granulocytotropic anaplasmosis, and human monocytotropic ehrlichiosis, developed guidelines to address the need for a consolidated source for the diagnosis and management of TBRD. The preparers focused on the practical aspects of epidemiology, clinical assessment, treatment, and laboratory diagnosis of TBRD. This report will assist clinicians and other health-care and public health professionals to 1) recognize epidemiologic features and clinical manifestations of TBRD, 2) develop a differential diagnosis that includes and ranks TBRD, 3) understand that the recommendations for doxycycline are the treatment of choice for both adults and children, 4) understand that early empiric antibiotic therapy can prevent severe morbidity and death, and 5) report suspect or confirmed cases of TBRD to local public health authorities to assist them with control measures and public health education efforts.

Background: Pharmaceutical company representatives (PCRs) influence the prescribing habits and professional behaviour of physicians. However, the skills for interacting with PCRs are not taught in the traditional medical school curriculum. We examined whether an innovative, mandatory workshop for third year medical students had immediate effects on knowledge and attitudes regarding interactions with PCRs., Methods: Surveys issued before and after the workshop intervention solicited opinions (five point Likert scales) from third year students (n = 75) about the degree of bias in PCR information, the influence of PCRs on prescribing habits, the acceptability of specific gifts, and the educational value of PCR information for both practicing physicians and students. Two faculty members and one PCR led the workshop, which highlighted typical physician-PCR interactions, the use of samples and gifts, the validity and legal boundaries of PCR information, and associated ethical issues. Role plays with the PCR demonstrated appropriate and inappropriate strategies for interacting with PCRs., Results: The majority of third year students (56%, 42/75) had experienced more than three personal conversations with a PCR about a drug product since starting medical school. Five percent (4/75) claimed no previous personal experience with PCRs. Most students (57.3%, 43/75) were not aware of available guidelines regarding PCR interactions. Twenty-eight percent of students (21/75) thought that none of the named activities/gifts (lunch access, free stethoscope, textbooks, educational CD-ROMS, sporting events) should be restricted, while 24.0% (8/75) thought that students should be restricted only from sporting events. The perceived educational value of PCR information to both practicing physicians and students increased after the workshop intervention from 17.7% to 43.2% (chi square, p = .0001), and 22.1% to 40.5% (p = .0007), respectively. Student perceptions of the degree of bias of PCR information decreased from 84.1% to 72.9% (p = .065), but the perceived degree of influence on prescribing increased (44.2% to 62.1% (p = .02))., Conclusions: Students have exposure to PCRs early in their medical training. A single workshop intervention may influence student attitudes toward interactions with PCRs. Students were more likely to acknowledge the educational value of PCR interactions and their impact on prescribing after the workshop intervention.

Ticks, including many that bite humans, are hosts to several obligate intracellular bacteria in the spotted fever group (SFG) of the genus Rickettsia. Only Rickettsia rickettsii, the agent of Rocky Mountain spotted fever, has been definitively associated with disease in humans in the United States. Herein we describe disease in a human caused by Rickettsia parkeri, an SFG rickettsia first identified >60 years ago in Gulf Coast ticks (Amblyomma maculatum) collected from the southern United States. Confirmation of the infection was accomplished using serological testing, immunohistochemical staining, cell culture isolation, and molecular methods. Application of specific laboratory assays to clinical specimens obtained from patients with febrile, eschar-associated illnesses following a tick bite may identify additional cases of R. parkeri rickettsiosis and possibly other novel SFG rickettsioses in the United States.

Clostridium difficile, a spore-forming toxigenic bacterium, is one of the most common causes of infectious diarrhea and colitis in the United States. Most patients with C. difficile infection have recently received antimicrobial therapy--usually clindamycin, cephalosporins, or the extended-spectrum penicillins. Clinical presentation varies from asymptomatic colonization to mild diarrhea to severe colitis. The mainstay of diagnosis is detection of C. difficile toxin A, toxin B, or both with a cytotoxin test or enzyme immunoassay of the stool of patients who have received antibiotic therapy and have features of C. difficile-associated diarrhea. Enzyme immunoassays that detect both toxins are preferred because of their higher diagnostic accuracy. If the first assay is negative and C. difficile-associated diarrhea is strongly suspected, a second assay may be performed. Ten days of oral metronidazole is the preferred therapy for most initial infections. Vancomycin is considered second-line therapy because of its cost and potential to select for vancomycin resistance. About 20% to 25% of patients experience reinfection or relapse after initial therapy and require retreatment. The disease can best be prevented by limiting the use of broad-spectrum antibiotics and adhering to control techniques.

Giardia lamblia is one of the most common parasitic infections. Although standard treatments are usually curative, some immunocompromised patients, including patients with acquired immunodeficiency syndrome as well as healthy patients, have giardiasis that is refractory to recommended regimens. We report our experience with 6 patients with giardiasis, for whom therapy with a combination of quinacrine and metronidazole resulted in cures for 5 of the 6 patients.

Purpose: To obtain reliable estimates of the sensitivity and specificity of the cervical Papanicolaou (Pap) smear and wet mount to diagnose vaginal trichomoniasis., Methods: Articles indexed in MEDLINE (1976-1998) about diagnostic tests for trichomoniasis and their listed references were retrieved. Thirty studies (9,501 patients) that used trichomonas culture as a gold standard were selected. Studies were defined as level I if they fulfilled at least two of the following three criteria: consecutive patients were evaluated prospectively, the decision to culture was not influenced by test results, and there was independent and blind comparison with culture. Studies were classified as level II if one criterion was fulfilled, and as level III otherwise., Results: The pooled sensitivity of the Pap smear for the diagnosis of trichomoniasis among level I studies was 57% (95% confidence interval [CI]: 51% to 63%) and the pooled specificity was 97% (95% CI: 93% to 100%). The likelihood ratio for a positive Pap smear was 19 among level I studies (range: 8 to 62). The pooled sensitivity of the wet mount among level I studies was 58% (95% CI: 51% to 66%); among level II studies, the sensitivity was 72% (95% CI: 62% to 81%), and among level III studies, the sensitivity was 82% (95% CI: 67% to 97%). The overall specificity of the wet mount was 99.8%., Conclusions: A positive Pap smear for trichomonads in settings in which trichomoniasis is common (prevalence > or =20%) requires treatment. A positive Pap smear is indeterminate when the prevalence of trichomoniasis is about 10%; thus, clinicians should either confirm the diagnosis by culture or treat all such patients, recognizing that some patients will be treated unnecessarily. A culture should be obtained in women with a positive Pap smear who are unlikely to have trichomoniasis (prevalence < or =1%). While a positive wet mount is diagnostic, a negative wet mount does not exclude trichomoniasis.

The first reported case of Clostridium septicum myonecrosis in an adult with aplastic anemia is described. The patient presented with sepsis, a parapharyngeal abscess that necessitated emergent intubation, and severe intravascular hemolysis attributed to clostridial alpha-toxin production. Despite prompt recognition and treatment, the patient died of his infection. C. septicum myonecrosis should be considered in any immunocompromised patient with sepsis, especially when accompanied by evidence of multiple sites of tissue infection.

Human phagocytes recognize bacterial LPS (endotoxin) through membrane CD14 (mCD14), a proinflammatory LPS receptor. This study tested the hypothesis that anti-LPS Abs neutralize endotoxin by blocking cellular uptake through mCD14. Ab-associated changes in the uptake and cellular distribution of FITC-LPS were assessed by flow cytometry and laser scanning confocal microscopy in human CD14-transfected Chinese hamster ovary fibroblasts (CHO-CD14 cells) and human peripheral blood monocytes. LPS core- and O-side chain-specific mAbs inhibited mCD14-mediated LPS uptake by both cell types in the presence of serum. O-side chain-specific mAb concurrently enhanced complement-dependent LPS uptake by monocytes through complement receptor-1 (CR1) and uptake by CHO-CD14 cells involving another heat-labile serum factor(s) and cell-associated recognition molecule(s). Core-specific mAb inhibited mCD14-mediated uptake of homologous and heterologous LPS, while producing less concurrent enhancement of non-mCD14-mediated LPS uptake. The modulation by anti-LPS mAbs of mCD14-mediated LPS uptake was associated with inhibition of LPS-induced nuclear factor-kappaB (NF-kappaB) translocation and TNF-alpha secretion in CHO-CD14 cells and monocytes, respectively, while mAb enhancement of non-mCD14-mediated LPS uptake stimulated these activities. LPS-specific Abs thus mediate anti-inflammatory and proinflammatory functions, respectively, by preventing target cell uptake of LPS through mCD14 and augmenting uptake through CR1 or other cell receptors.

Medical preparation of travelers to overseas locations is an important part of military medical care. We reviewed pre-travel records of patients attending the travel clinic at the National Naval Medical Center (NNMC) and used a post-travel questionnaire to determine the most frequent medical problems associated with international travel. Among 1,416 individuals who received pre-travel care at NNMC, there were 760 (54%) males and 656 (46%) females, the median patient age was 48 years, the most common reason for travel was pleasure, and the median duration of travel was 21 days. The most common destinations were Asia (27%), Africa (15%), Europe (13%), Central America/Caribbean (12%), and South America (11%). The median number of immunizations prescribed was three. Malaria chemoprophylaxis was prescribed to 45%. The average cost of vaccines and medications to medically prepare a traveler was $67. Among 271 (82%) who returned the post-travel questionnaire, the most common illnesses reported were diarrhea (23%) and upper respiratory infections (19%); medical treatment was sought by 9%. Properly informed, military physicians can provide a valuable service at a reasonable cost to reduce the risk of travel-acquired medical problems and illnesses.

Lipopolysaccharide (LPS)-monocyte/macrophage interactions are central to the infected host's inflammatory response to gram-negative bacteria. Flow cytometry was used to analyze the regulation by LPS-specific monoclonal antibodies (MAbs) of fluorescein isothiocyanate-conjugated LPS uptake by human peripheral blood monocytes. The uptake of LPS was stimulated by fresh or heat-inactivated serum (NHS or delta NHS) or by LPS-binding protein and inhibited by alpha-LPS or alpha-CD14 (LPS receptor) MAbs. The inhibition of alpha-LPS uptake was offset in the presence of NHS by a simultaneous MAb-mediated increase in LPS uptake that was blocked by alpha-complement receptor 1. Monocyte tumor necrosis factor-alpha responses to LPS were augmented by NHS and delta NHS and inhibited by alpha-LPS MAbs. Thus, alpha-LPS MAbs down-regulate the proinflammatory uptake of LPS by human monocytes via membrane-bound CD14 while promoting complement-mediated opsonic uptake through membrane-associated CR1.

Troops stationed in the Middle East during Operations Desert Shield/Storm were potentially exposed to leishmaniasis, a parasitic infection transmitted by sandflies. In this region, infection primarily causes cutaneous and, less often, visceral disease. Visceral leishmaniasis, which typically has an incubation period of several months, can be a difficult diagnosis as it presents with a wide range of symptoms and there are no non-invasive, reliable diagnostic tests. Cutaneous leishmaniasis is more easily diagnosed using culture and stained smears of biopsy and aspirate samples from skin lesions. Pentavalent antimonials are most often used to treat leishmaniasis; however, treatment is potentially toxic and not recommended except in cases of documented disease.