Showing papers in "Clinical Infectious Diseases in 2003"
TL;DR: A meta-analysis was performed to summarize the impact of methicillin-resistance on mortality in Staphylococcus aureus bacteremia and explored the reasons for heterogeneity by means of subgroup analyses.
Abstract: A meta-analysis was performed to summarize the impact of methicillin-resistance on mortality in Staphylococcus aureus bacteremia. A search of the MEDLINE database for studies published during the period of 1 January 1980 through 31 December 2000 and a bibliographic review identified English-language studies of S. aureus bacteremia. Studies were included if they contained the numbers of and mortality rates for patients with methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) bacteremia. Data were extracted on demographic characteristics of the patients, adjustment for severity and comorbid illness, source of bacteremia, and crude and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for in-hospital mortality. When the results were pooled with a random-effects model, a significant increase in mortality associated with MRSA bacteremia was evident (OR, 1.93; 95% CI, 1.54-2.42; P<.001); significant heterogeneity was present. We explored the reasons for heterogeneity by means of subgroup analyses. MRSA bacteremia is associated with significantly higher mortality rate than is MSSA bacteremia.
2,008 citations
TL;DR: Nosocomial candidemia is still associated with an extremely high crude and attributable mortality--much higher than that expected from underlying disease alone.
Abstract: We reexamined the attributable mortality of nosocomial candidemia 15 years after a retrospective cohort study performed at our hospital demonstrated an attributable mortality of 38%. For all episodes of nosocomial candidemia between 1 July 1997 and 30 June 2001, we matched control patients with case patients by age, sex, date of hospital admission, underlying disease(s), length of time at risk, and surgical procedure(s). We analyzed 108 matched pairs. There were no statistically significant differences in age, sex, underlying disease(s), time at risk, surgical procedure, or vital signs at admission between cases and controls. The crude mortality among case patients was 61% (66 of 108 patients), compared with 12% (13 of 108) among control patients, for an attributable mortality of 49% (95% CI, 38%-60%). Nosocomial candidemia is still associated with an extremely high crude and attributable mortality--much higher than that expected from underlying disease alone.
1,110 citations
TL;DR: Methicillin resistance is independently associated with increased mortality and hospital charges among patients with S. aureus SSI and has a greater duration of hospitalization after infection.
Abstract: Data for 479 patients were analyzed to assess the impact of methicillin resistance on the outcomes of patients with Staphylococcus aureus surgical site infections (SSIs). Patients infected with methicillin-resistant S. aureus (MRSA) had a greater 90-day mortality rate than did patients infected with methicillin-susceptible S. aureus (MSSA; adjusted odds ratio, 3.4; 95% confidence interval, 1.5-7.2). Patients infected with MRSA had a greater duration of hospitalization after infection (median additional days, 5; P<.001), although this was not significant on multivariate analysis (P=.11). Median hospital charges were 29,455 dollars for control subjects, 52,791 dollars for patients with MSSA SSI, and 92,363 dollars for patients with MRSA SSI (P<.001 for all group comparisons). Patients with MRSA SSI had a 1.19-fold increase in hospital charges (P=.03) and had mean attributable excess charges of 13,901 dollars per SSI compared with patients who had MSSA SSIs. Methicillin resistance is independently associated with increased mortality and hospital charges among patients with S. aureus SSI.
949 citations
TL;DR: It was decided that all of the information dealing with the initial empiric treatment regimens should be in tabular format with footnotes, and the topics selected for updating have been organized according to the headings used in the August 2000 CAP guidelines.
Abstract: The Infectious Diseases Society of America (IDSA) produced guidelines for community-acquired pneumonia (CAP) in immunocompetent adults in 1998 and again in 2000 [1, 2]. Because of evolving resistance to antimicrobials and other advances, it was felt that an update should be provided every few years so that important developments could be highlighted and pressing questions answered. We addressed those issues that the committee believed were important to the practicing physician, including suggestions for initial empiric therapy for CAP. In some cases, only a few paragraphs were needed, whereas, in others, a somewhat more in-depth discussion was provided. Because many physicians focus on the tables rather than on the text of guidelines, it was decided that all of the information dealing with the initial empiric treatment regimens should be in tabular format with footnotes (tables 1–3). The topics selected for updating have been organized according to the headings used in the August 2000 CAP guidelines pub-
949 citations
TL;DR: A meta-analysis of studies reporting the prevalence of community-acquired MRSA (CA-MRSA) among MRSA isolates from hospitalized patients or the prevalenceof MRSA colonization among community members suggested that effective control of dissemination of MRSA throughout the community likely will require effective controlOf nosocomial MRSA transmission.
Abstract: Reports suggest that carriage of methicillin-resistant Staphylococcus aureus (MRSA) among persons without health care-associated risks has increased. A meta-analysis of studies reporting the prevalence of community-acquired MRSA (CA-MRSA) among MRSA isolates from hospitalized patients or the prevalence of MRSA colonization among community members was conducted. The CA-MRSA prevalence among hospital MRSA was 30.2% in 27 retrospective studies and 37.3% in 5 prospective studies; 85% of all patients with CA-MRSA had > or =1 health care-associated risk. The pooled MRSA colonization rate among community members was 1.3% (95% confidence interval [CI], 1.04%-1.53%), but there was significant heterogeneity among study populations. Community members from whom samples were obtained in health care facilities were more likely to be carrying MRSA than were community members from whom samples were obtained outside of the health care setting (relative risk, 2.35; 95% CI, 1.56-3.53). Among studies that excluded persons with health care contacts, the MRSA prevalence was 0.2%. Moreover, most persons with CA-MRSA had > or =1 health care-associated risk, which suggests that the prevalence of MRSA among persons without risks remains low (< or =0.24%). Effective control of dissemination of MRSA throughout the community likely will require effective control of nosocomial MRSA transmission.
835 citations
University of Alabama at Birmingham1, University of Texas Health Science Center at Houston2, Veterans Health Administration3, University of Southern California4, Washington University in St. Louis5, University of Michigan6, Tulane University7, Ohio State University8, University of Mississippi Medical Center9, Westchester Medical Center10, University of California, Los Angeles11
TL;DR: Subjects in the observational cohort had higher Acute Physiology and Chronic Health Evaluation II scores than did participants in the clinical trial, which suggests that the former subjects are more often excluded from therapeutic trials.
Abstract: We conducted a prospective, multicenter observational study of adults (n=1447) and children (n=144) with candidemia at tertiary care centers in the United States in parallel with a candidemia treatment trial that included nonneutropenic adults. Candida albicans was the most common bloodstream isolate recovered from adults and children (45% vs. 49%) and was associated with high mortality (47% among adults vs. 29% among children). Three-month survival was better among children than among adults (76% vs. 54%; P<.001). Most children received amphotericin B as initial therapy, whereas most adults received fluconazole. In adults, Candida parapsilosis fungemia was associated with lower mortality than was non-parapsilosis candidemia (24% vs. 46%; P<.001). Mortality was similar among subjects with Candida glabrata or non-glabrata candidemia; mortality was also similar among subjects with C. glabrata candidemia who received fluconazole rather than other antifungal therapy. Subjects in the observational cohort had higher Acute Physiology and Chronic Health Evaluation II scores than did participants in the clinical trial (18.6 vs. 16.1), which suggests that the former subjects are more often excluded from therapeutic trials.
802 citations
TL;DR: Voriconazole has been approved for the treatment of invasive aspergillosis and refractory infections with Pseudallescheria/Scedosporium and Fusarium species, and it will likely become the drug of choice for treatment of serious infections with those filamentous fungi.
Abstract: Voriconazole is a second-generation azole antifungal agent that shows excellent in vitro activity against a wide variety of yeasts and molds. It can be given by either the intravenous or the oral route; the oral formulation has excellent bioavailability. The side effect profile of voriconazole is unique in that non-sight-threatening, transient visual disturbances occur in approximately 30% of patients given the drug. Rash (which can manifest as photosensitivity) and hepatitis also occur. The potential for drug-drug interactions is high and requires that careful attention be given to dosage regimens and monitoring of serum levels and effects of interacting drugs. Voriconazole has been approved for the treatment of invasive aspergillosis and refractory infections with Pseudallescheria/Scedosporium and Fusarium species, and it will likely become the drug of choice for treatment of serious infections with those filamentous fungi.
719 citations
Santa Clara Valley Medical Center1, Stanford University2, Veterans Health Administration3, Saint Louis University4, Northwestern University5, Medical University of South Carolina6, University of Manchester7, Swiss Institute of Allergy and Asthma Research8, Boston Children's Hospital9, Arnold Palmer Hospital for Children10
TL;DR: Virulence factors in Aspergillus that could aggravate these diseases, and particularly immunogenetic factors that could predispose persons to ABPA, were identified and diagnostic criteria that could provide a framework for monitoring were adopted.
Abstract: Because of the difficulties of recognizing allergic bronchopulmonary aspergillosis (ABPA) in the context of cystic fibrosis (because of overlapping clinical, radiographic, microbiologic, and immunologic features), advances in our understanding of the pathogenesis of allergic aspergillosis, new possibilities in therapy, and the need for agreed-upon definitions, an international consensus conference was convened. Areas addressed included fungal biology, immunopathogenesis, insights from animal models, diagnostic criteria, epidemiology, the use of new immunologic and genetic techniques in diagnosis, imaging modalities, pharmacology, and treatment approaches. Evidence from the existing literature was graded, and the consensus views were synthesized into this document and recirculated for affirmation. Virulence factors in Aspergillus that could aggravate these diseases, and particularly immunogenetic factors that could predispose persons to ABPA, were identified. New information has come from transgenic animals and recombinant fungal and host molecules. Diagnostic criteria that could provide a framework for monitoring were adopted, and helpful imaging features were identified. New possibilities in therapy produced plans for managing diverse clinical presentations.
647 citations
TL;DR: Voriconazole is an effective and well-tolerated treatment for refractory or less-common invasive fungal infections and as primary treatment for patients with infections for which there is no approved therapy.
Abstract: Treatments for invasive fungal infections remain unsatisfactory. We evaluated the efficacy, tolerability, and safety of voriconazole as salvage treatment for 273 patients with refractory and intolerant-to-treatment fungal infections and as primary treatment for 28 patients with infections for which there is no approved therapy. Voriconazole was associated with satisfactory global responses in 50% of the overall cohort; specifically, successful outcomes were observed in 47% of patients whose infections failed to respond to previous antifungal therapy and in 68% of patients whose infections have no approved antifungal therapy. In this population at high risk for treatment failure, the efficacy rates for voriconazole were 43.7% for aspergillosis, 57.5% for candidiasis, 38.9% for cryptococcosis, 45.5% for fusariosis, and 30% for scedosporiosis. Voriconazole was well tolerated, and treatment-related discontinuations of therapy or dose reductions occurred for <10% of patients. Voriconazole is an effective and well-tolerated treatment for refractory or less-common invasive fungal infections.
622 citations
Indiana University – Purdue University Indianapolis1, University of Wisconsin-Madison2, Washington University in St. Louis3, University of Cincinnati4, University of Colorado Denver5, Brown University6, University of Minnesota7, University of California, Los Angeles8, Cleveland Clinic9, Cornell University10
TL;DR: This work presents a meta-analysis of data from 12 adult AIDS Clinical Trials Group Cardiovascular Subcommittee studies that shows clear trends in prognosis, disease progression, and mortality in men and women with HIV/AIDS over a 12-year period.
Abstract: Michael P. Dube, James H. Stein, Judith A. Aberg, Carl J. Fichtenbaum, John G. Gerber, Karen T. Tashima, W. Keith Henry, Judith S. Currier, Dennis Sprecher, and Marshall J. Glesby, for the Adult AIDS Clinical Trials Group Cardiovascular Subcommittee Indiana University, Indianapolis; University of Wisconsin, Madison; Washington University, St. Louis, Missouri; University of Cincinnati and Cleveland Clinic, Ohio; University of Colorado, Denver; Brown University, Providence, Rhode Island; University of Minnesota, St. Paul; University of California at Los Angeles; and Cornell University, New York, New York
619 citations
TL;DR: Patients with YMDD variants losing clinical response with a significant increase in the HBV DNA and ALT levels may require additional therapy.
Abstract: YMDD variants of hepatitis B virus (HBV) emerge in some patients with chronic hepatitis B who receive lamivudine. YMDD variants were examined in 794 patients in 4 controlled studies of 1 year's duration. The long-term effects of YMDD variants were examined in a subset of patients treated up to 4 years. YMDD variants were detected by polymerase chain reaction (PCR) and restriction fragment-length polymorphism assays. After 1 year, YMDD variants were detected in 81 (24%) of 335 patients. In these patients, the median serum HBV DNA concentration at 1 year was <20% of the baseline level, and serum alanine transaminase (ALT) levels and liver histologic findings had significantly improved. In patients with YMDD variants who were treated for up to 4 years, median HBV DNA and ALT levels showed improvements. Sex, baseline body mass index, and HBV DNA level were associated with emergence of YMDD variants. Patients with YMDD variants losing clinical response with a significant increase in the HBV DNA and ALT levels may require additional therapy.
TL;DR: A total of 2340 patients with underlying malignancy were identified among 22,631 episodes of nosocomial bloodstream infections in a prospectively collected database for 49 hospitals in the United States, and the predominant pathogens were coagulase-negative staphylococci.
Abstract: A total of 2340 patients with underlying malignancy were identified among 22,631 episodes of nosocomial bloodstream infections (BSIs) in a prospectively collected database for 49 hospitals in the United States (Surveillance and Control of Pathogens of Epidemiologic Importance [SCOPE] Project). Data were obtained for the period of March 1995 through February 2001. Gram-positive organisms accounted for 62% of all BSIs in 1995 and for 76% in 2000 (P<.001), and gram-negative organisms accounted for 22% and 14% of all BSIs for these years, respectively. Neutropenia was observed in 30% of patients, so neutropenic and nonneutropenic patients were compared. In both, the predominant pathogens were coagulase-negative staphylococci (32% of isolates recovered from neutropenic patients and 30% of isolates recovered from nonneutropenic patients). The source of BSI was not determined for 57% of patients. The crude mortality rate was 36% for neutropenic patients and 31% for nonneutropenic patients.
TL;DR: How antimicrobial resistance can affect patient outcomes by enhancing virulence, causing a delay in the administration of appropriate therapy, and limiting available therapy is explored.
Abstract: Despite an increasing prevalence of antimicrobial-resistant pathogens, the health and economic impact of colonization and infection with these organisms has not been fully elucidated. We explore how antimicrobial resistance can affect patient outcomes by enhancing virulence, causing a delay in the administration of appropriate therapy, and limiting available therapy. Next, we examine the different perspectives held by hospitals, third-party payers, patients, and society on the impact of resistance. Finally, we review methodological issues in designing and assessing studies that address the clinical outcomes for patients infected or colonized with resistant pathogens, including adjustment for important confounding variables, control group selection, and the quantification of economic outcomes.
TL;DR: Findings support the notion that delay of therapy has deleterious effects on clinical outcomes, and efforts should be made to ensure that appropriate therapy is initiated promptly.
Abstract: The objective of this study was to determine the effect of delayed therapy on morbidity and mortality associated with nosocomial Staphylococcus aureus bacteremia. The study included all episodes of S. aureus bacteremia that developed >2 days after hospital admission during 1999 to 2001. Classification and regression tree analysis (CART) was used to select the mortality breakpoint between early and delayed treatment. During the 25-month study period, 167 patients met the inclusion criteria. The breakpoint between delayed and early treatment derived using CART was 44.75 hours. On multivariate analysis, delayed treatment was found to be an independent predictor of infection-related mortality (odds ratio, 3.8; 95% confidence interval, 1.3-11.0; P=.01) and was associated with a longer hospital stay than was early treatment (20.2 days versus 14.3 days; P=.05). These findings support the notion that delay of therapy has deleterious effects on clinical outcomes, and efforts should be made to ensure that appropriate therapy is initiated promptly.
TL;DR: The evidence that better prescribing can reduce resistance rates is mixed, and although changes to hospital regimens may reduce one resistance problem, other opportunistic bacteria may fill the vacant niche; the best that can reasonably be anticipated is an improved balance between the accumulation of resistance and new antibacterial development.
Abstract: The basic mechanisms of antibacterial resistance are well known, but critical new aspects continue to be discovered. Recently discovered factors with major implications for the emergence, dissemination, and maintenance of resistance include multidrug efflux, hypermutability, integrons, and plasmid addiction. Some resistances are widespread and others local, with prevalence rates often worst in newly prosperous countries and in those specialist units where antibacterial use is heaviest. Multidrug-resistant epidemic strains are critical to the total accumulation of resistance (e.g., among Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus, Klebsiella pneumoniae), but it remains unclear why some bacterial lineages achieve epidemic spread whereas others that are equally resistant do not. The correlation between in vitro resistance and treatment failure is imperfect, but resistance undoubtedly increases mortality, morbidity, and costs in many settings. Recent concern has led to a plethora of governmental and agency reports advocating less antibacterial use, better antibacterial use, better infection control, and the development of new antibacterials. The evidence that better prescribing can reduce resistance rates is mixed, and although changes to hospital regimens may reduce one resistance problem, other opportunistic bacteria may fill the vacant niche. Overall, the best that can reasonably be anticipated is an improved balance between the accumulation of resistance and new antibacterial development.
TL;DR: Patients with recurrent C. difficile colitis may benefit from the introduction of stool from healthy donors via a nasogastric tube, according to retrospectively reviewed medical records.
Abstract: Clostridium difficile‐associated diarrhea and colitis have emerged as major complications associated with use of systemic antimicrobials. In this study, the medical records for 18 subjects who received donor stool by nasogastric tube for recurrent C. difficile infection during a 9-year period at a single institution were retrospectively reviewed. During the period between the initial diagnosis of C. difficile colitis and the stool treatments, the 18 subjects received a total of 64 courses of antimicrobials (range, 2–7 courses; median, 3 courses). During the 90 days after receipt of treatment with stool, 2 patients died of unrelated illnesses. One of the 16 survivors experienced a single recurrence of C. difficile colitis during 90-day follow-up. No adverse effects associated with stool treatment were observed. Patients with recurrent C. difficile colitis may benefit from the
TL;DR: Delays in starting effective antimicrobial therapy for P. aeruginosa bacteremia tended to be associated with higher mortality, and there was a trend toward higher mortality as the length of delay increased.
Abstract: Among the nosocomial pathogens, Pseudomonas aeruginosa is recognized as a major cause of morbidity and mortality. Data on 136 patients with P. aeruginosa bacteremia were retrospectively analyzed to evaluate risk factors for mortality. The median age of the patients was 55 years (range, 15-85 years), 78.7% of the cases were hospital-acquired, and the 30-day mortality rate was 39% (53 of 136 patients). Multivariate analysis demonstrated that risk factors for mortality included severe sepsis, pneumonia, delay in starting effective antimicrobial therapy, and an increasing APACHE II score (all P values <.05). In 123 of the 136 patients (excluding 13 patients treated with inadequate definitive antibiotics), 30-day mortality was 27.7% (13 of 47 patients) in the group of patients who received initially effective empirical antimicrobial therapy, and 43.4% (33 of 76) in the group of patients who received delayed effective antimicrobial therapy (P=.079). There was a trend toward higher mortality as the length of delay increased. Delay in starting effective antimicrobial therapy for P. aeruginosa bacteremia tended to be associated with higher mortality.
Harvard University1, University of British Columbia2, Brigham and Women's Hospital3, Vanderbilt University Medical Center4, University of Rochester5, Columbia University6, University of Alabama at Birmingham7, University of Pittsburgh8, International AIDS Society9, University of California, San Diego10
TL;DR: The International AIDS Society-USA convened a panel of physicians and scientists with expertise in antiretroviral drug management, HIV-1 drug resistance, and patient care to provide updated recommendations for HIV- 1 resistance testing.
Abstract: New information about the benefits and limitations of testing for resistance to human immunodeficiency virus (HIV) type 1 (HIV-1) drugs has emerged. The International AIDS Society-USA convened a panel of physicians and scientists with expertise in antiretroviral drug management, HIV-1 drug resistance, and patient care to provide updated recommendations for HIV-1 resistance testing. Published data and presentations at scientific conferences, as well as strength of the evidence, were considered. Properly used resistance testing can improve virological outcome among HIV-infected individuals. Resistance testing is recommended in cases of acute or recent HIV infection, for certain patients who have been infected as long as 2 years or more prior to initiating therapy, in cases of antiretroviral failure, and during pregnancy. Limitations of resistance testing remain, and more study is needed to refine optimal use and interpretation.
TL;DR: Vigilance regarding the detection of possible rare cases of infection due to probiotics should be maintained, and isolates should be sent to reference centers for molecular characterization and confirmation.
Abstract: Lactobacilli and bifidobacteria are extremely rare causes of infection in humans, as are probiotics based on these organisms. This lack of pathogenicity extends across all age groups and to immunocompromised individuals. Strains used for new probiotics should be chosen from the commensal flora of humans and should not carry intrinsic resistance to antibiotics that would prevent treatment of a rare probiotic infection. Vigilance regarding the detection of possible rare cases of infection due to probiotics should be maintained, and isolates should be sent to reference centers for molecular characterization and confirmation.
TL;DR: Bacterial vaginosis was a strong predictor of gonorrhea and chlamydial infection among subjects who reported recent exposure to a male partner with urethritis, and the importance of vaginal flora in the defense against STD acquisition is supported.
Abstract: To evaluate whether bacterial vaginosis predicts the acquisition of sexually transmitted diseases (STDs), we studied 255 nonpregnant female subjects aged 15-30 who reported recent sexual contact with a male partner in whom either gonococcal or chlamydial urethritis or nongonococcal urethritis was diagnosed. Compared to subjects with normal vaginal flora, subjects with bacterial vaginosis were more likely to test positive for Neisseria gonorrhoeae (odds ratio [OR], 4.1; 95% confidence interval [CI], 1.7-9.7) and Chlamydia trachomatis (OR, 3.4; 95% CI, 1.5-7.8). Subjects colonized vaginally by hydrogen peroxide-producing lactobacilli were less likely to receive a diagnosis of chlamydial infection or gonorrhea than subjects without such lactobacilli. Bacterial vaginosis was a strong predictor of gonorrhea and chlamydial infection among subjects who reported recent exposure to a male partner with urethritis. These data support the importance of vaginal flora in the defense against STD acquisition.
TL;DR: Although statistical significance was not reached in the primary end point, the trial provides further support for IVIG as an efficacious adjunctive therapy in STSS.
Abstract: The efficacy and safety of high-dose intravenous polyspecific immunoglobulin G (IVIG) as adjunctive therapy in streptococcal toxic shock syndrome (STSS) were evaluated in a multicenter, randomized, double-blind, placebo-controlled trial. The trial was prematurely terminated because of slow patient recruitment, and results were obtained from 21 enrolled patients (10 IVIG recipients and 11 placebo recipients). The primary end point was mortality at 28 days, and a 3.6-fold higher mortality rate was found in the placebo group. A significant decrease in the sepsis-related organ failure assessment score at days 2 (P = .02) and 3 (P = .04) was noted in the IVIG group. Furthermore, a significant increase in plasma neutralizing activity against superantigens expressed by autologous isolates was noted in the IVIG group after treatment (P = .03). Although statistical significance was not reached in the primary end point, the trial provides further support for IVIG as an efficacious adjunctive therapy in STSS.
TL;DR: The results of studies on the modes of influenza transmission and their relevant isolation precautions are reviewed and limited evidence is available to support the relative clinical importance of contact, droplet, and droplet nuclei (airborne) transmission of influenza.
Abstract: Annual influenza epidemics in the United States result in an average of >36,000 deaths and 114,000 hospitalizations. Influenza can spread rapidly to patients and health care personnel in health care settings after influenza is introduced by visitors, staff, or patients. Influenza outbreaks in health care facilities can have potentially devastating consequences, particularly for immunocompromised persons. Although vaccination of health care personnel and patients is the primary means to prevent and control outbreaks of influenza in health care settings, antiviral influenza medications and isolation precautions are important adjuncts. Although droplet transmission is thought to be the primary mode of influenza transmission, limited evidence is available to support the relative clinical importance of contact, droplet, and droplet nuclei (airborne) transmission of influenza. In this article, the results of studies on the modes of influenza transmission and their relevant isolation precautions are reviewed.
University of Cincinnati1, Washington University in St. Louis2, Stanford University3, University of Virginia4, University of Washington5, University of Georgia6, Georgia Regents University7, Centers for Disease Control and Prevention8, Tufts University9, University of British Columbia10, Johns Hopkins University School of Medicine11
TL;DR: This work presents a meta-analysis of 125 cases of Clostridium difficile infection in mice over a 12-month period and shows clear patterns of disease progression that are consistent with tick-borne disease and suggest fungal infection.
Abstract: Joseph S. Solomkin, John E. Mazuski, Ellen J. Baron, Robert G. Sawyer, Avery B. Nathens, Joseph T. DiPiro, Timothy Buchman, E. Patchen Dellinger, John Jernigan, Sherwood Gorbach, Anthony W. Chow, and John Bartlett Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio; Department of Surgery, Washington University School of Medicine, St. Louis, Missouri; Department of Microbiology, Stanford University School of Medicine, Palo Alto, California; Department of Surgery, University of Virginia, Charlottesville; Department of Surgery, University of Washington, Seattle; University of Georgia College of Pharmacy, Department of Surgery, Medical College of Georgia, Augusta, and Centers for Disease Control and Prevention, Atlanta; Department of Medicine, Tufts University School of Medicine, Boston, Massachusetts; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland; and Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
TL;DR: Intravenous colistin appears to be a safe and effective alternative to imipenem for the management of VAP due to carbapenem-resistant strains of A. baumannii.
Abstract: We prospectively evaluated the efficacy and toxicity of intravenously administered colistin in 35 episodes of ventilator-associated pneumonia (VAP) due to multidrug-resistant Acinetobacter baumannii. Microbiological diagnosis was performed with use of quantitative culture. In 21 patients, the episodes were caused by a strain susceptible exclusively to colistin (the CO group) and were all treated with this antimicrobial intravenously. In 14 patients, the episodes were caused by strains that remained susceptible to imipenem and were treated with imipenem-cilastatin (the IM group). Acute Physiology and Chronic Health Evaluation II scores at the time of admission and Sequential Organ Failure Assessment scores at time of diagnosis were similar in both groups. VAP was considered clinically cured in 57% of cases in both groups. In-hospital mortality rates were 61.9% in the CO group and 64.2% in the IM group, and the VAP-related mortality rates were 38% and 35.7%, respectively. Four patients in the CO group and 6 in the IM group developed renal failure. Neurophysiological evaluation was performed during 12 episodes in the CO group, but it revealed no signs of neuromuscular blockade. Intravenous colistin appears to be a safe and effective alternative to imipenem for the management of VAP due to carbapenem-resistant strains of A. baumannii.
TL;DR: Indicators of good long-term medical outcomes were mild symptoms, thin-walled quiescent cavities, residual pleural fibrosis, and normal inflammatory markers.
Abstract: We describe 18 nonimmunocompromised patients with chronic pulmonary aspergillosis. Duration of the disease ranged from several months to 112 years. All 18 patients had prior pulmonary disease. Weight loss, chronic cough (often with hemoptysis and shortness of breath), fatigue, and chest pain were the most common symptoms. All 18 patients had cavities, usually multiple and in 1 or both upper lobes of the lung, that expanded over time, with or without intraluminal fungal balls. All had detectable Aspergillus precipitins and inflammatory markers. Elevated levels of total immunoglobulin E were seen in 78% of patients and of Aspergillus-specific immunoglobulin E in 64%. Directed lung biopsies showed chronic inflammation, necrosis, or granulomas without hyphal invasion. Antifungal therapy with itraconazole resulted in 71% of patients improved or stabilized, with relapse common. Interferon-g treatment was useful in 3 patients. In azole nonresponders, modest responses to intravenous amphotericin B (80%) followed by itraconazole were seen. Surgery removed disease but postoperative pleural aspergillosis was inevitable. Indicators of good long-term medical outcomes were mild symptoms, thin-walled quiescent cavities, residual pleural fibrosis, and normal inflammatory markers.
TL;DR: A cumulative adherence of 70%-89%, a CD4 cell nadir of <200 cells/microL, and the missing of a scheduled clinic visit in the past month were independently associated with an increased hazard of viral rebound with clinically significant resistance.
Abstract: Nonadherence to highly active antiretroviral therapy (HAART) is a major cause of human immunodeficiency virus (HIV) drug resistance; however the level of nonadherence associated with the greatest risk of resistance is unknown. Beginning in February 2000, 195 patients at the Johns Hopkins Outpatient Center (Baltimore, MD) who were receiving HAART and who had HIV loads of <500 copies/mL were recruited into a cohort study and observed for 1 year. At each visit, adherence to HAART was assessed and plasma samples were obtained and stored for resistance testing, if indicated. The overall incidence of viral rebound with clinically significant resistance was 14.5 cases per 100 person-years. By multivariate Cox proportional hazards regression, a cumulative adherence of 70%-89%, a CD4 cell nadir of <200 cells/microL, and the missing of a scheduled clinic visit in the past month were independently associated with an increased hazard of viral rebound with clinically significant resistance. Clinicians and patients must set high adherence goals to avoid the development of resistance.
University of Texas at Austin1, AstraZeneca2, University of Alabama at Birmingham3, Beth Israel Deaconess Medical Center4, Wayne State University5, UCLA Medical Center6, University of Mississippi Medical Center7, Westchester Medical Center8, Beaumont Hospital9, Thomas Jefferson University10, University of Arkansas for Medical Sciences11, University of Illinois at Chicago12, Indiana University13, University of Minnesota14, Tulane University15, University of Miami16, Community Medical Center17, Massachusetts Institute of Technology18, University of Virginia19, Hospital of the University of Pennsylvania20, Houston Methodist Hospital21, Albert Einstein College of Medicine22, LSU Health Sciences Center Shreveport23
TL;DR: In nonneutropenic subjects, the combination of fluconazole plus AmB was not antagonistic compared with flu Conazole alone, and the combination trended toward improved success and more-rapid clearance from the bloodstream.
Abstract: A randomized, blinded, multicenter trial was conducted to compare fluconazole (800 mg per day) plus placebo with fluconazole plus amphotericin B (AmB) deoxycholate (0.7 mg/kg per day, with the placebo/AmB component given only for the first 5-6 days) as therapy for candidemia due to species other than Candida krusei in adults without neutropenia. A total of 219 patients met criteria for a modified intent-to-treat analysis. The groups were similar except that those who were treated with fluconazole plus placebo had a higher mean (+/- standard error) Acute Physiology and Chronic Health Evaluation II score (16.8+/-0.6 vs. 15.0+/-0.7; P=.039). Success rates on study day 30 by Kaplan-Meier time-to-failure analysis were 57% for fluconazole plus placebo and 69% for fluconazole plus AmB (P=.08). Overall success rates were 56% (60 of 107 patients) and 69% (77 of 112 patients; P=.043), respectively; the bloodstream infection failed to clear in 17% and 6% of subjects, respectively (P=.02). In nonneutropenic subjects, the combination of fluconazole plus AmB was not antagonistic compared with fluconazole alone, and the combination trended toward improved success and more-rapid clearance from the bloodstream.
University of Pittsburgh1, National Yang-Ming University2, Johannesburg Hospital3, Karolinska Institutet4, Mayo Clinic5, University of Buenos Aires6, Tufts University7, The Chinese University of Hong Kong8, National Cheng Kung University9, University of Rio Grande10, Emory University11, National Health Laboratory Service12
TL;DR: In this paper, the authors performed a prospective, international, observational study of 844 hospitalized patients with blood cultures positive for Streptococcus pneumoniae and evaluated the impact of concordant antibiotic therapy (i.e., receipt of a single antibiotic with in vitro activity against S. pneumoniae) versus discordant therapy (inactive in vitro) on mortality at 14 days.
Abstract: We performed a prospective, international, observational study of 844 hospitalized patients with blood cultures positive for Streptococcus pneumoniae. Fifteen percent of isolates had in vitro intermediate susceptibility to penicillin (minimum inhibitory concentration [MIC], 0.12-1 microg/mL), and 9.6% of isolates were resistant (MIC, >or=2 microg/mL). Age, severity of illness, and underlying disease with immunosuppression were significantly associated with mortality; penicillin resistance was not a risk factor for mortality. The impact of concordant antibiotic therapy (i.e., receipt of a single antibiotic with in vitro activity against S. pneumoniae) versus discordant therapy (inactive in vitro) on mortality was assessed at 14 days. Discordant therapy with penicillins, cefotaxime, and ceftriaxone (but not cefuroxime) did not result in a higher mortality rate. Similarly, time required for defervescence and frequency of suppurative complications were not associated with concordance of beta-lactam antibiotic therapy. beta-Lactam antibiotics should still be useful for treatment of pneumococcal infections that do not involve cerebrospinal fluid, regardless of in vitro susceptibility, as determined by current NCCLS breakpoints.
TL;DR: This cohort descriptive study summarizes the epidemiological, clinical, and laboratory characteristics of the Rift Valley fever epidemic that occurred in Saudi Arabia from 26 August 2000 through 22 September 2001 and found patients with leukopenia had significantly a lower mortality rate than did those with a normal or high leukocyte count.
Abstract: This cohort descriptive study summarizes the epidemiological, clinical, and laboratory characteristics of the Rift Valley fever (RVF) epidemic that occurred in Saudi Arabia from 26 August 2000 through 22 September 2001. A total of 886 cases were reported. Of 834 reported cases for which laboratory results were available, 81.9% were laboratory confirmed, of which 51.1% were positive for only RVF immunoglobulin M, 35.7% were positive for only RVF antigen, and 13.2% were positive for both. The mean age (+/- standard deviation) was 46.9+/-19.4 years, and the ratio of male to female patients was 4:1. Clinical and laboratory features included fever (92.6% of patients), nausea (59.4%), vomiting (52.6%), abdominal pain (38.0%), diarrhea (22.1%), jaundice (18.1%), neurological manifestations (17.1%), hemorrhagic manifestations (7.1%), vision loss or scotomas (1.5%), elevated liver enzyme levels (98%), elevated lactate dehydrogenase level (60.2%), thrombocytopenia (38.4%), leukopenia (39.7%), renal impairment or failure (27.8%), elevated creatine kinase level (27.3%), and severe anemia (15.1%). The mortality rate was 13.9%. Bleeding, neurological manifestations, and jaundice were independently associated with a high mortality rate. Patients with leukopenia had significantly a lower mortality rate than did those with a normal or high leukocyte count (2.3% vs. 27.9%; odds ratio, 0.09; 95% confidence interval, 0.01-0.63).
TL;DR: Prosthetic joint infections (PJIs) occur in approximately 1.5%-2.5% of all primary hip or knee arthroplasties and the mortality rate attributed to PJIs may be as high as 2.5%.
Abstract: Prosthetic joint infections (PJIs) occur in ∼1.5%–2.5% of all primary hip or knee arthroplasties. The mortality rate attributed to PJIs may be as high as 2.5%. Substantial morbidity is associated with a loss of mobility, although this is temporary. The costs associated with a single episode of PJI are ∼$50,000 per episode, exclusive of lost wages. Risk factors that increase the occurrence of PJI include revision arthroplasty, time in the operating room, postoperative surgical site infection, and malignancy. Pain is the most consistent symptom. Staphylococcus species are the most common organisms isolated from PJI sites. Two-stage revision is superior to single-stage revision or to debridement with prosthesis retention. Long-term antibiotic suppression and/or arthrodesis are useful for patients too frail to undergo extensive surgery. Using an optimal approach, recurrent infection occurs in !10% of previously infected joints. Prosthetic joint infections (PJIs) of total hip arthroplasty (THA) or total knee arthroplasty (TKA) occur with an incidence of 1.5%–2.5% for primary THA or TKA, respectively, whereas revision THA or TKA carries a respective infection risk of 3.2% or 5.6% [1] (table 1). The estimated cost of treating an infected arthroplasty is 1$50,000 per episode [2]. The attendant mortality was estimated, in the 1970s and 1980s, to be between 2.7% and 18% [2] in older patients. More current studies have estimated the mortality attendant to surgical intervention for PJI to be 0.4%–1.2% for 65-year-old patients and 2%–7% for 80-year-old patients [3]. Fisman et al. [3] estimated a 2-fold increase in the probability of death during the 3 months after resection arthroplasty. The mortality reported since 1989 has ranged between 1% and 2.7% [4–10]. Berbari et al. [2] performed a large case-controlled prospective study of patients undergoing THA at the Mayo Clinic between 1969 and 1991. They reported that the 4 most significant factors predictive of PJI were (1) postoperative surgical site infection (OR, 35.9), (2) a National Nosocomial Infection