Search

Background Autoimmunity is a common cause of pulmonary fibrosis and can present either as a manifestation of an established connective tissue disease or as the recently described entity of interstitial pneumonia with autoimmune features. The rate of progression and responsiveness to immunosuppression in these illnesses are difficult to predict. Circulating fibrocytes are bone marrow-derived progenitor cells that home to injured tissues and contribute to lung fibrogenesis. We sought to test the hypothesis that the blood fibrocyte concentration predicts outcome and treatment responsiveness in autoimmune interstitial lung diseases. Methods We compared the concentration of circulating fibrocytes in 50 subjects with autoimmune interstitial lung disease and 26 matched healthy controls and assessed the relationship between serial peripheral blood fibrocyte concentrations and clinical outcomes over a median of 6.25 years. Results As compared to controls, subjects with autoimmune interstitial lung disease had higher circulating concentrations of total fibrocytes, the subset of activated fibrocytes, and fibrocytes with activation of PI3K/AKT/mTOR, transforming growth factor-β (TGF-β) receptor and interleukin (IL)-4/IL-13 receptor signalling pathways. Over the follow-up period, there were episodes of marked elevation in the concentration of circulating fibrocytes in subjects with autoimmune interstitial lung disease but not controls. Initiation of immunosuppressive therapy was associated with a decline in the concentration of circulating fibrocytes. For each 100 000 cells·mL−1 increase in peak concentration of circulating fibrocytes, we found a 5% increase in odds of death or lung function decline. Conclusion In patients with autoimmune interstitial lung disease, circulating fibrocytes may represent a biomarker of outcome and treatment response., Autoimmune diseases are common causes of pulmonary fibrosis. The blood concentration of fibrocytes, cells involved in formation of scar tissue, predicts outcomes and response to immunosuppression in these patients. https://bit.ly/35bel62

Legionnaires’ disease is commonly diagnosed clinically using a urinary antigen test. The urinary antigen test is highly accurate for L. pneumophila serogroup 1, however other diagnostic tests should also be utilized in conjunction with the urinary antigen as many other Legionella species and serogroups are pathogenic. Culturing of patient specimens remains the gold standard for diagnosis of Legionnaires’ disease. Selective media, BYCE with the addition of antibiotics, allows for a high sensitivity and specificity. Culturing can identify all species and serogroups of Legionella. A major benefit of culturing is that it provides the recovery of a patient isolate, which can be used to find an environmental match. Other diagnostic tests, including DFA and molecular tests such as PCR and LAMP, are useful tests to supplement culturing. Molecular tests provide much more rapid results in comparison to culture, however these tests should not be a primary diagnostic tool given their lower sensitivity and specificity in comparison to culturing. It is recommended that all laboratories develop the ability to culture patient specimens in-house with the selective media.

Background. Postobstructive community-acquired pneumonia (PO-CAP) is relatively common in clinical practice. The clinical syndrome is poorly defined, and the role of infection as a cause of the infiltrate is uncertain. We prospectively studied patients with PO-CAP and compared them to a cohort of patients with bacterial community-acquired pneumonia (B-CAP). Methods. We prospectively studied patients hospitalized for CAP; 5.4% had PO-CAP, defined as a pulmonary infiltrate occurring distal to an obstructed bronchus. Sputum and blood cultures, viral polymerase chain reaction, urinary antigen tests, and serum procalcitonin (PCT) were done in nearly all cases. Clinical and laboratory characteristics of patients with PO-CAP were compared to those of patients with B-CAP. Results. In a 2-year period, we identified 30 patients with PO-CAP. Compared to patients with B-CAP, patients with PO-CAP had longer duration of symptoms (median, 14 vs 5 days; P < .001). Weight loss and cavitary lesions were more common (P < .01 for both comparisons) and leukocytosis was less common (P < .01) in patients with PO-CAP. A bacterial pathogen was implicated in only 3 (10%) PO-CAP cases. PCT was

Background. A prolonged course of antibiotic therapy is often initiated for chronic rhinosinusitis (CRS) based on symptomatology. We examined differences in clinical manifestations and underlying conditions in patients with symptoms typical for CRS. CT scan abnormality of the sinuses was the gold standard for diagnosis of CRS. Methods. We performed a prospective observational study of 125 adults with classic symptoms of CRS undergoing nasal endoscopy and sinus CT. Results. The patients were classified into 2 groups: (1) those with radiographic evidence of sinusitis by CT (Sx 1 CT) (75) and (2) those with normal CT scans of the sinus (Sx ‐ CT) (50). Decreased smell was significantly more common in Sx 1 CT than in Sx ‐ CT patients, (P 5 .003). Paradoxically, headache, facial pain, and sleep disturbance occurred significantly more frequently in patients with Sx ‐ CT than in patients with Sx 1 CT (P , .05). The absence of mucopurulence on endoscopy proved to be highly specific for Sx ‐ CT patients (100%). On the other hand, sensitivity was low; only 24% of Sx 1 CT patients demonstrated mucopurulence by endoscopy. Improvement in response to antibiotics was similar between both CRS categories. Conclusions. Most symptoms considered to be typical for CRS proved to be nonspecific. Interestingly, symptoms that were more severe were significantly more likely to occur in younger patients who were Sx ‐ CT. The efficacy of antibiotic therapy was uncertain. We suggest that objective evidence of mucopurulence assessed by endoscopy or CT should be obtained if antibiotics are to be given for prolonged duration. We recommend a moratorium for the widespread practice of a prolonged course of empiric antibiotics in patients with presumed CRS.

Hospital-acquired Legionnaires' disease is directly linked to the presence ofLegionellain hospital drinking water. Disinfecting the drinking water system is an effective preventive measure. The efficacy of any disinfection measures should be validated in a stepwise fashion from laboratory assessment to a controlled multiple-hospital evaluation over a prolonged period of time. In this review, we evaluate systemic disinfection methods (copper-silver ionization, chlorine dioxide, monochloramine, ultraviolet light, and hyperchlorination), a focal disinfection method (point-of-use filtration), and short-term disinfection methods in outbreak situations (superheat-and-flush with or without hyperchlorination). The infection control practitioner should take the lead in selection of the disinfection system and the vendor. Formal appraisals by other hospitals with experience of the system under consideration is indicated. Routine performance of surveillance cultures of drinking water to detectLegionellaand monitoring of disinfectant concentrations are necessary to ensure long-term efficacy.

Central nervous system (CNS) cryptococcosis is most commonly encountered among HIV-infected and other immunosuppressed hosts but is less well-characterized among non-immunosuppressed patients.We conducted a three year, prospective, observational study to compare the clinical manifestations and outcome of CNS cryptococcosis in three patient populations: HIV-infected patients (n = 54), HIV-negative immunosuppressed patients (n = 21), and non-immunosuppressed patients (n = 11).Time from initial symptoms to presentation did not differ between the groups. HIV-infected patients were significantly more likely to present with fevers (p 0.0001), but were less likely to have abnormal mental status, CNS mass lesions and pulmonary involvement (p = 0.001, 0.01 and 0.03, respectively). The clinical manifestations among HIV-negative immunosuppressed patients were generally intermediate to the other groups. Overall, acuity of illness was worse among non-immunosuppressed patients, as measured by APACHE II scores (p = 0.02). Intracranial pressure was higher in HIV-infected and non-immunosuppressed patients than immunosuppressed patients (p = 0.008 and 0.01, respectively). Repeated lumbar punctures were more common among HIV-infected patients (p = 0.01). There was a trend toward more frequent placement of permanent CNS shunts among non-HIV patients (p = 0.05). The mortality rate was greatest for non-immunosuppressed patients (p = 0.04).CNS cryptococcosis in non-immunosuppressed patients was associated with poorer prognosis. Our findings suggest that host immune responses may contribute to pathogenesis of CNS cryptococcosis, with more intact immune function associated with increased CNS-related morbidity and overall mortality.

Two nonsynchronous events have affected the management of community-acquired pneumonia (CAP): spiraling empiricism for CAP and the "golden era" of clinical microbiology. The development of broad-spectrum antibiotics has led to widespread empiric use without ascertaining the etiology of the infecting microbe. Unfortunately, this approach clashes with the second event, which is the advent of molecular-based microbiology that can identify the causative pathogen rapidly at the point of care. The urinary antigen is a most effective rapid test that has allowed targeted therapy for Legionnaire disease at the point of care. The high specificity (> 90%) allows the clinician to administer appropriate anti-Legionella therapy based on a single rapid test; however, its low sensitivity (76%) means that a notable number of cases of Legionnaire disease will go undiagnosed if other tests, especially culture, are not performed. Further, culture for Legionella is not readily available. If a culture is not performed, epidemiologic identification of the source of the bacterium cannot be ascertained by molecular fingerprinting of the patient and the putative source strain. We recommend resurrection of the basic principles of infectious disease, which are to identify the microbial etiology of the infection and to use narrow, targeted antimicrobial therapy. To reduce antimicrobial overuse with subsequent antimicrobial resistance, these basic principles must be applied in concert with traditional and newer tests in the clinical microbiology laboratory.

Given the nonspecific clinical manifestations of Legionnaires' disease and the high mortality of untreated Legionnaires' disease, we recommend routine use of Legionella testing, especially the Legionella urinary antigen test, for all patients with community-acquired pneumonia. This includes patients with ambulatory pneumonia and hospitalized children. Legionella cultures should be more widely available, especially in hospitals where the drinking water is colonized with Legionella. Azithromycin or levofloxacin can be considered as first-line therapy. Other antibiotics including tetracyclines, tigecycline, other fluoroquinolones and other macrolides (especially clarithromycin) are also effective. The clinical response of quinolones may be somewhat more favorable compared to macrolides, but the outcome is similar. If the Legionnaires' disease is hospital-acquired, culturing of the hospital drinking water for Legionella is indicated.

Patients with chronic obstructive pulmonary disease (COPD) may progress to community-acquired pneumonia (CAP), but there has been no formal study of the factors responsible. We studied the influence of severity of underlying lung disease, pathogen characteristics and the ratio of the area under the concentration–time curve from 0–24 h to minimum inhibitory concentration (AUC24/MIC), i.e. the area under the inhibitory curve (AUIC), during the progression from acute exacerbation of chronic bronchitis (AECB) in COPD to CAP. The model parameters were derived from a multinational database of 3885 patients with AECB or CAP (April 1996 to July 2006). Patients with underlying COPD were evaluated in two separate analyses: infection progression between COPD and CAP within Global Initiative for Chronic Obstructive Lung Disease (GOLD)-like grouping (GLG); and distribution of pathogen by GLG, CAP and AECB. Secondary analyses examined the impact of target AUIC attainment on progression to CAP for Streptococcus pneumoniae. The relative impact of GLG and AUIC were modelled in multivariate logistic regression for S. pneumoniae. Progression to CAP linked directly with GLG I/II, III and IV (18.3%, 31.7% and 48.9%, respectively; P < 0.001). Progression to CAP was strongly associated with S. pneumoniae (57.3%), whilst other pathogens were predominant in AECB that did not progress to CAP (61.7%) (P = 0.002). AUIC ≥100 was associated with AECB (65.1%) and AUIC

Previous studies showed that temperature and total organic carbon in drinking water would cause chlorine dioxide (ClO(2)) loss in a water distribution system and affect the efficiency of ClO(2) for Legionella control. However, among the various causes of ClO(2) loss in a drinking water distribution system, the loss of disinfectant due to the reaction with corrosion scales has not been studied in detail. In this study, the corrosion scales from a galvanized iron pipe and a copper pipe that have been in service for more than 10 years were characterized by energy dispersive spectroscopy (EDS) and X-ray diffraction (XRD). The impact of these corrosion scale materials on ClO(2) decay was investigated in de-ionized water at 25 and 45 degrees C in a batch reactor with floating glass cover. ClO(2) decay was also investigated in a specially designed reactor made from the iron and copper pipes to obtain more realistic reaction rate data. Goethite (alpha-FeOOH) and magnetite (Fe(3)O(4)) were identified as the main components of iron corrosion scale. Cuprite (Cu(2)O) was identified as the major component of copper corrosion scale. The reaction rate of ClO(2) with both iron and copper oxides followed a first-order kinetics. First-order decay rate constants for ClO(2) reactions with iron corrosion scales obtained from the used service pipe and in the iron pipe reactor itself ranged from 0.025 to 0.083 min(-1). The decay rate constant for ClO(2) with Cu(2)O powder and in the copper pipe reactor was much smaller and it ranged from 0.0052 to 0.0062 min(-1). Based on these results, it can be concluded that the corrosion scale will cause much more significant ClO(2) loss in corroded iron pipes of the distribution system than the total organic carbon that may be present in finished water.

In a 30-month prospective study, we evaluated the efficacy of chlorine dioxide to control Legionella organisms in a water distribution system of a hospital with 364 patient beds and 74 skilled nursing beds. The number of hot water specimens positive for Legionella organisms decreased from 12 (60%) of 20 to 2 (10%) of 20. An extended time (18 months) was needed to achieve a significant reduction in the rate of Legionella positivity among hot water specimens. At the time of writing, no cases of hospital-acquired Legionnaires disease have been detected at the hospital since the chlorine dioxide system was installed in January 2003. Use of chlorine dioxide was safe, based on Environmental Protection Agency limits regarding maximum concentrations of chlorine dioxide and chlorite.

Summary Objectives The objectives of this study were to investigate the clinical and laboratory features, hospital course and outcome of patients with bacteraemic pneumococcal pneumonia, comparing HIV with non-HIV patients, as well as HIV patients from different parts of the world. Methods This was a multicentre prospective observational study of consecutive adult cases with bacteraemic pneumococcal pneumonia in 10 countries on 6 continents. Results A total of 768 cases were recruited, of which 200 were HIV-infected; 166 were from South Africa. Lower age, IV drug use, fewer co-morbid illnesses, and a higher frequency of respiratory symptoms were significantly more likely to occur in HIV patients. The 14-day mortality for the group as a whole was 14.5%, being 16% in the HIV patients and 13.9% in the non-HIV patients (not significant). When adjustments were made for age and severity of illness, HIV patients had significantly higher 14-day mortality with significant trend for increasing 14-day mortality in those with lower CD4 counts. Despite differences in various clinical and laboratory parameters in patients from different parts of the world, on multivariate analysis, when adjusting for regional differences, the HIV-infected patients were still noted to have poorer 14-day mortality. Conclusions This study, in contrast to previous investigations, indicates that there are significant differences in the clinical presentation and outcome of bacteraemic pneumococcal pneumonia when comparing HIV and non-HIV patients.

Received 6 September 2006; accepted 6 September 2006;electronically published 13 September 2006.Author affiliations are listed at the end of the text.Reprints or correspondence: Dr. Elias J. Anaissie, MyelomaInstitute for Research and Therapy, University of Arkansasfor Medical Sciences, 4301 W. Markham, Slot 816, LittleRock, AR 72205 (anaissieeliasj@uams.edu).

Antimicrobe.org (http://www.antimicrobe.org) is a World Wide Web-based version of the textbook Antimicrobial Therapy and Vaccines, volumes I and II. The Web site currently consists of 3 texts (Microbes, Antimicrobial Agents, and HIV Clinical Manual) and will soon include a fourth, Empiric. The Web site focuses on therapy for infectious diseases, and it covers, in comprehensive detail, a great majority of infections encountered today. The dynamic nature of a Web-based reference allows for information to be frequently updated and enhances a physician's searching capabilities to find answers to very specific clinical questions and the latest available evidence. A Smart Search engine allows users to ask specific questions and to find focused answers, either within the textbook or through PubMed via a guided PubMed references option. The Web site also provides clinical vignettes and minireviews on hot topics in infectious diseases and hyperlinks to other important articles or Web sites. Chapters are written by experts in their field who provide evidence-based information, as well as anecdotal reports about rare infections. Antimicrobe.org would be of great benefit to physicians who treat infections on a routine basis.

The diagnosis of ventilator-associated pneumonia has been clouded by uncertainty, because a reference standard has never been established. The use of invasive procedures to obtain respiratory tract samples for culture, with quantitation of the bacteria isolated, has been the approach most commonly advocated. Quantitation of bacteria from lower respiratory tract specimens can be used to distinguish colonization from infection. We review the invasive procedures (bronchoalveolar lavage, protected specimen brushing, nonbronchoscopic bronchoalveolar lavage, and blinded bronchial sampling), the methods of quantitation used, the types of catheters used, the sample collection methods, and the criteria used as cutoffs for the quantitative cultures. Quantitation of lower respiratory tract samples is inherently unstable from a mathematical perspective, given the variability in the volume of fluid instilled and reaspirated and the magnitude and complexity of the area being sampled. We also briefly review the use of quantitation for bacterial infections other than pneumonia, including urinary tract infection and catheter-related bacteremia. The variability in both the methods and reference criteria in the studies reviewed show that the quantitation approach is neither standardized nor evidence based.

Aims: Stagnation is widely believed to predispose water systems to colonization by Legionella. A model plumbing system was constructed to determine the effect of flow regimes on the presence of Legionella within microbial biofilms. Methods and Results: The plumbing model contained three parallel pipes where turbulent, laminar and stagnant flow regimes were established. Four sets of experiments were carried out with Reynolds number from 10 000 to 40 000 and from 355 to 2000 in turbulent and laminar pipes, respectively. Legionella counts recovered from biofilm and planktonic water samples of the three sampling pipes were compared with to determine the effect of flow regime on the presence of Legionella. Significantly higher colony counts of Legionella were recovered from the biofilm of the pipe with turbulent flow compared with the pipe with laminar flow. The lowest counts were in the pipe with stagnant flow. Conclusions: We were unable to demonstrate that stagnant conditions promoted Legionella colonization. Significance and Impact of the Study: Plumbing modifications to remove areas of stagnation including deadlegs are widely recommended, but these modifications are tedious and expensive to perform. Controlled studies in large buildings are needed to validate this unproved hypothesis.

Background. Staphylococcus aureus is frequently isolated from urine samples obtained from long-term care patients. The significance of staphylococcal bacteriuria is uncertain. We hypothesized that S. aureus is a urinary pathogen and that colonized urine could be a source of future staphylococcal infection. Methods. We performed a cohort study of 102 patients at a long-term care Veterans Affairs facility for whom S. aureus had been isolated from clinical urine culture. Patients were observed via urine and nasal cultures that were performed every 2 months. We determined the occurrence of (1) symptomatic urinary tract infection concurrent with isolation of S. aureus (by predetermined criteria), (2) staphylococcal bacteremia concomitant with isolation of S. aureus from urine, and (3) subsequent episodes of staphylococcal infection. Results. Of 102 patients, 82% had undergone recent urinary catheterization. Thirty-three percent of patients had symptomatic urinary tract infection at the time of initial isolation of S. aureus, and 13% were bacteremic. Eight-six percent of the initial urine isolates were methicillin-resistant S. aureus. Seventy-one patients had followup culture data; 58% of cultures were positive for S. aureus at 2 months (median duration of staphylococcal bacteriuria, 4.3 months). Sixteen patients had subsequent staphylococcal infections, occurring up to 12 months after initial isolation of S. aureus; 8 late-onset infections were bacteremic. In 5 of 8 patients, the late blood isolate was found to have matched the initial urine isolate by pulsed-field gel electrophoresis typing. Conclusions. S. aureus is a cause of urinary tract infection among patients with urinary tract catheterization. The majority of isolates are methicillin-resistant S. aureus. S. aureus bacteriuria can lead to subsequent invasive infection. The efficacy of antistaphylococcal therapy in preventing late-onset staphylococcal infection in patients with persistent staphylococcal bacteriuria should be tested in controlled trials.

Following the first outbreaks of legionnaire's disease, erythromycin emerged as the treatment of choice without the foundation of rigorous clinical trials. The number of therapeutic failures with erythromycin, as well as the side-effects and drug interactions, led to the consideration of other drugs such as the new macrolides and quinolones for the treatment of legionnaire's disease in the 1990s. In this article, 19 studies in in-vitro intracellular models and seven animal studies that compared macrolides to quinolones were reviewed. Quinolones were found to have greater activity in intracellular models and improved efficacy in animal models compared with macrolides. No randomised trials comparing the clinical efficacy of the new macrolides and new quinolones have ever been performed. Three observational studies totalling 458 patients with legionnaire's disease have compared the clinical efficacy of macrolides (not including azithromycin) and quinolones (mainly levofloxacin). The results suggested that quinolones may produce a superior clinical response compared with the macrolides (erythromycin and clarithromycin) with regard to defervescence, complications, and length of hospital stay. Little data exist for direct comparison of quinolones and azithromycin.

The ideal diagnostic approach for ventilator-associated pneumonia currently is based on invasive procedures to obtain respiratory tract cultures. Given the lack of consensus and relatively poor acceptance of full bronchoscopic bronchoalveolar lavage (BAL) and protected specimen brush (PSB), less invasive procedures have been developed. We review the nonbronchoscopic procedures (nonbronchoscopic bronchoalveolar lavage, including mini-BAL, blinded protected specimen, and blinded bronchial sampling) and endotracheal aspiration. We provide a critique of the methods used, the types of catheters inserted, and the sample collection methods. Most studies were flawed in that antibiotic use before initiation of the procedure was not controlled. The variability of both the methods and the criteria for the gold standard in the numerous investigations show that these procedures are neither standardized nor proven to be accurate and often did not improve management. Pending future studies, use of endotracheal aspirates without the use of quantitation seems to be a reasonable approach for clinicians who are not committed to an invasive procedure.

Background The Allegheny County Health Department (ACHD) in Pennsylvania distributed the first guidelines for prevention and control of health care–acquired Legionnaires' disease (LD) by 1995. The proactive approach advocated in the guidelines differed notably from that of the Centers for Disease Control and Prevention (CDC) by recommending routine environmental testing of the hospital water distribution system even when cases of health care–acquired Legionnaires' disease had never been identified. Objectives Our purpose was to (1) evaluate the impact of the ACHD guidelines on the Legionella diagnostic and preventive practices of health care facilities in Allegheny and surrounding counties and (2) compare the incidence of health care–acquired LD before and after issuance of the ACHD guidelines. Methods CDC case reports of LD from 1991 to 2001 were tabulated and compiled by the ACHD Infectious Disease Unit and the Association for Professionals in Infection Control and Epidemiology, Inc, Three Rivers Chapter. A survey was distributed to 110 hospitals and long-term care facilities in the region. The results were analyzed as occurring either in the preguideline period (1991-1994) or postguideline period (1995-2001). Results A significant decrease in the number of health care–acquired cases was demonstrated between the preguideline (33%) and postguideline (9%) periods ( P =.0001). In contrast, community-acquired cases increased from 67% pre guideline to 91% post guideline. A total of 71% of the facilities were colonized with Legionella. Disinfection of the water distribution system was initiated by 44% of facilities. Use of urinary antigen testing significantly increased from 40% pre guideline to 79% post guideline ( P =.0001). Conclusions Health care–acquired LD declined significantly after the issuance of guidelines for prevention and control of health care–acquired LD. The decline was associated with health care facilities performing routine environmental monitoring of their water distribution systems followed by the initiation of disinfection methods if indicated. Two unanticipated benefits were (1) cases of LD in the community and long-term care facilities were uncovered as a result of increased availability of Legionella tests and (2) litigation and unfavorable publicity involving ACHD hospitals ceased.

Pneumonia is a leading cause of morbidity and mortality in nursing home patients. In acute care hospitals, there is considerable evidence to indicate that Legionnaires' disease is a significant cause of nosocomial pneumonia, the source of which is the potable water system. A relatively limited amount of data exists as to the role of Legionnaires' disease as a cause of pneumonia acquired in long-term care residents. Several lines of evidence suggest that Legionnaires' disease may be an important but underrecognized cause of pneumonia in long-term care residents. These include reports of outbreaks, prospective studies of community-acquired pneumonia that include nursing home patients, and prospective studies of individual long-term care facilities linking Legionnaires' disease to colonization of the potable water system with Legionella. Multiinstitutional studies combining environmental and clinical surveillance for Legionella are needed to further confirm the relationship between colonization of potable water and the occurrence of disease in the long-term care facilities. Until these studies are completed, it is recommended that individual facilities undertake annual sampling of the potable water system for Legionella, coupled with introduction of the rapid Legionella urinary antigen test should L. pneumophila serogroup 1 be found.

The comparative in vitro activity of quinolones (trovafloxacin, gemifloxacin, levofloxacin, ciprofloxacin, moxifloxacin and grepafloxacin), ketolides (ABT-773 and telithromycin) and macrolides (clarithromycin, azithromycin and erythromycin) were evaluated against Legionella pneumophila by broth dilution and an HL-60 intracellular model. The MIC90 of the quinolones, clarithromycin and ABT-773 were more than eight times lower than for erythromycin. Telithromycin, ABT-773 and azithromycin had significantly greater intracellular activity against L. pneumophila than erythromycin at 1xMIC and 8xMIC. The rank order of intracellular activity against L. pneumophila serogroup 1 was quinolones>ketolides>macrolides. Clinical trials to determine the clinical efficacy of ketolides for the treatment of Legionnaires' disease are warranted.

The Global Infectious Diseases and Epidemiology Network (GIDEON) (http://www.gideononline.com) consists of 4 modules. The first is designed to generate a ranked differential diagnosis list for any infectious diseases scenario in any of 220 countries. The second follows the country-specific epidemiology of 337 individual diseases. The third presents a comprehensive encyclopedia of 308 generic anti-infective drugs and vaccines, including a listing of >9500 trade names. The fourth generates a ranked identification list based on the phenotype of bacteria, mycobacteria, and yeasts. The program performs well and serves as a useful paradigm for World Wide Web-based informatics. GIDEON is an eclectic program that can serve the needs of clinicians, epidemiologists, and microbiologists working in the fields of infectious diseases and geographic medicine.

Background Contaminated computer keyboards have been acknowledged as a potential source for bacterial transmission between health care providers and patients. Biosafe HM 4100 is an antimicrobial polymer that can be incorporated into the polyurethane material used to make keyboard covers. This study aimed to determine whether plastic keyboard covers containing HM 4100 effectively minimize the survival of bacterial species commonly present on health care environmental surfaces. Methods Polyurethane material that contained 0.5% HM 4100, 1% HM 4100, and 1% HM 4100 with spray coating of 1% HM 4100 were tested. In 2 separate experiments, the surfaces of test materials were inoculated with suspensions of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecalis (VREF), Escherichia coli , or Pseudomonas aeruginosa . Viability was assessed on the materials at 0, 10, 30, 60, 120, and 240 minutes after inoculation. Results Maximum reductions in viability were observed for all 4 organisms at the longest tested time period on each test material. Mean reductions on the 0.5% HM 4100 material at 240 minutes were 99.99% for E coli , 97.8% for MRSA, 95.0% for VREF, and 92.1% for P aeruginosa . Mean reductions on the 1% HM 4100 at 120 minutes were 99.9% for VREF, 99.9% for MRSA, 99.9% for P aeruginosa , and 99.5% for E coli . Mean reductions on the 1% HM 4100 plus spray coating at 30 minutes were 99.9% for E coli , 99.8% for VREF, 98.8% for P aeruginosa , and 97.2% for MRSA. Conclusions Incorporation of the HM 4100 antimicrobial polymer into polyurethane keyboard material may reduce the hand carriage of bacteria between health care providers and patients.

Background: Although fluoroquinolones possess excellent in vitro activity against Legionella, few large-scale clinical trials have examined their efficacy in the treatment of Legionnaires disease. Even fewer studies have applied rigorous criteria for diagnosis of community-acquired Legionnaires disease, including culture of respiratory secretions on selective media. Methods: Data from six clinical trials encompassing 1,997 total patients have been analyzed to determine the efficacy of levofloxacin (500 mg qd or 750 mg qd) in treating patients with community-acquired pneumonia (CAP) due to Legionella. Results: Of the 1,997 total patients with CAP from the clinical trials, 75 patients had infection with a Legionella species. Demographics showed a large portion of these patients were < 55 years of age and nonsmokers. More than 90% of mild-to-moderate and severe cases of Legionella infection resolved clinically at the posttherapy visit, 2 to 14 days after treatment termination. No deaths were reported for any patient with Legionnaires disease treated with levofloxacin during the studies. Conclusions: Levofloxacin was efficacious at both 500 mg for 7 to 14 days and 750 mg for 5 days. Legionnaires disease is not associated only with smokers, the elderly, and the immunosuppressed, but also has the potential to affect a broader demographic range of the general population than previously thought. (CHEST 2004; 125:2135–2139)

Linezolid is an alternative to vancomycin for the long-term treatment of gram-positive bacterial orthopedic infections because of its antibacterial spectrum and oral bioavailability, but duration-related myelosuppression could offset its advantages. To evaluate the hematologic effects of these agents, we prospectively studied 65 consecutive adults with gram-positive bacterial orthopedic infections requiring > or =2 weeks of vancomycin therapy (n=52) or linezolid therapy (n=20). Trends suggesting higher incidence of hematologic effects among the patients receiving vancomycin were not significant, regardless of whether the end point was lowest cell count during therapy or change from baseline. The only difference was a higher incidence of thrombocytopenia (

Malignant (necrotising) external otitis is an invasive infection of the external auditory canal. Although elderly patients with diabetes remain the population most commonly affected, immunosuppressed individuals (eg, from HIV infection, chemotherapy, etc) are also susceptible to malignant external otitis. Pseudomonas aeruginosa is isolated from the aural drainage in more than 90% of cases. The pathophysiology is incompletely understood although aural water exposure (eg, irrigation for cerumen impaction) has been reported as a potential iatrogenic factor. The typical patient presents with exquisitely painful otorrhoea. If untreated, cranial neuropathies (most commonly of the facial nerve) can develop due to subtemporal extension of the infection. The diagnosis of malignant external otitis is based on a combination of clinical findings, an increased erythrocyte sedimentation rate, and radiographic evidence of soft tissue with or without bone erosion in the external canal and infratemporal fossa. Treatment consists of prolonged administration (6-8 weeks) of an antipseudomonal agent (typically an orally administered quinolone). With the introduction and widespread use of both oral and topical quinolones, there are reports of less severe presentation of malignant external otitis and even the emergence of ciprofloxacin resistance. Reservation of systemic quinolones for the treatment of invasive ear infections is recommended.

Staphylococcus aureus bacteremia is associated with substantial morbidity. Recurrence is common, but incidence and risk factors for recurrence are uncertain. The emergence of methicillin resistance and the ease of administering vancomycin, especially in patients who have renal insufficiency, have led to reliance on this drug with the assumption that it is as effective as beta-lactam antibiotics, an assumption that remains open to debate. We initiated a multicenter, prospective observational study in 6 university hospitals and enrolled 505 consecutive patients with S. aureus bacteremia. All patients were monitored for 6 months and patients with endocarditis were followed for 3 years. Recurrence was defined as return of S. aureus bacteremia after documentation of negative blood cultures and/or clinical improvement after completing a course of antistaphylococcal antibiotic therapy. All blood isolates taken from patients with recurrent bacteremia underwent pulsed-field gel electrophoresis testing. Recurrence was subclassified as reinfection (different pulsed-field gel electrophoresis patterns) or relapse (same pulsed-field gel electrophoresis pattern).Forty-two patients experienced 56 episodes of recurrence (79% were relapses and 21% were reinfection). Relapse occurred earlier than reinfection (median, 36 versus 99 d, p < 0.06). Risk factors for relapse of S. aureus bacteremia included valvular heart disease, cirrhosis of the liver, and deep-seated infection (including endocarditis). Nafcillin was superior to vancomycin in preventing bacteriologic failure (persistent bacteremia or relapse) for methicillin-susceptible S. aureus (MSSA) bacteremia. Failure to remove infected intravascular devices/catheters and vancomycin therapy were common factors in patients experiencing multiple (greater than 2) relapses. However, by multivariate analysis, only endocarditis and therapy with vancomycin (versus nafcillin) were significantly associated with relapse. Recurrences occurred in 9.4% of S. aureus bacteremias following antistaphylococcal therapy, and most were relapses. Duration of antistaphylococcal therapy was not associated with relapse, but type of antibiotic therapy was. Nafcillin was superior to vancomycin in efficacy in patients with MSSA bacteremia.

Background and Objectives:Hospital-acquired legionnaires' disease can be prevented by disinfection of hospital water systems. This study assessed the long-term efficacy of copper-silver ionization as a disinfection method in controllingLegionellain hospital water systems and reducing the incidence of hospital-acquired legionnaires' disease. A standardized, evidence-based approach to assist hospitals with decision making concerning the possible purchase of a disinfection system is presented.Design:The first 16 hospitals to install copper-silver ionization systems forLegionelladisinfection were surveyed. Surveys conducted in 1995 and 2000 documented the experiences of the hospitals with maintenance of the system, contamination of water withLegionella, and occurrence of hospital-acquired legionnaires' disease. All were acute care hospitals with a mean of 435 beds.Results:All 16 hospitals reported cases of hospital-acquired legionnaires' disease prior to installing the copper-silver ionization system. Seventy-five percent had previously attempted other disinfection methods including superheat and flush, ultraviolet light, and hyperchlorination. By 2000, the ionization systems had been operational from 5 to 11 years. Prior to installation, 47% of the hospitals reported that more than 30% of distal water sites yieldedLegionella. In 1995, after installation, 50% of the hospitals reported 0% positivity, and 43% still reported 0% in 2000. Moreover, no cases of hospital-acquired legionnaires' disease have occurred in any hospital since 1995.Conclusions:This study represents the final step in a proposed 4-step evaluation process of disinfection systems that includes (1) demonstrated efficacy ofLegionellaeradication in vitro using laboratory assays, (2) anecdotal experiences in preventing legionnaires' disease in individual hospitals, (3) controlled studies in individual hospitals, and (4) validation in confirmatory reports from multiple hospitals during a prolonged time (5 to 11 years in this study). Copper-silver ionization is now the only disinfection modality to have fulfilled all four evaluation criteria.

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.

BACKGROUND: There has never been a cross-Canada surveillance project to determine the rate ofLegionellaspecies as a cause of community-acquired pneumonia requiring hospitalization and to determine whether there are any regional differences in the rates of Legionnaires' disease in Canada. Anecdotally, Legionnaires' disease is thought to be uncommon in Western Canada.METHODS: From January, 1996 through to October 31, 1997, a prospective study of the etiology of community acquired pneumonia requiring admission to 15 tertiary care hospitals in eight Canadian provinces was conducted. A urine sample from each patient was tested forLegionella pneumophilaserogroup 1 antigen using a commercially available ELISA assay. A culture of sputum or other respiratory specimens for Legionellaceae was carried out at the discretion of the attending physician. Two hundred thirty-four patients had acute and 6-week convalescent serum samples tested for antibodies toL pneumophilaserogroups 1 through 6 using an ELISA method.RESULTS: 28 of the 850 patients (3.2%) had Legionnaires' disease; 18 of 823 (2.1%) were positive forL pneumophilaserogroup 1 by urinary antigen testing. The rate of Legionnaires' disease, based on urinary antigen, at the Halifax site was higher than that at the other sites (seven of 163 patients versus 11 of 660 [P=0.04]). Of the 28 cases of Legionnaires' disease identified using all methods, 11 of 277 patients (3.9%) were enrolled from Western provinces versus 17 of 573 patients (2.9%) from Eastern provinces (P=nonsignificant).CONCLUSIONS: Legionnaires' disease is just as common in Western as in Eastern Canada.L pneumophilaserogroup 1 may be more common in Halifax than at the other sites studied.

Copper-silver (Cu-Ag) ionization has effectively controlled Legionella spp. in the hot water systems of numerous hospitals. However, it was ineffective at controlling Legionella in one Ohio hospital despite the confirmation of adequate total concentrations of copper and silver ions. The pH of the water at this hospital was found to be 8.5 to 9.0. The purpose of this study was to investigate the impact of pH and other water quality parameters, including alkalinity (HCO 3 − ), hardness (Ca 2+ and Mg 2+ ), and amount of dissolved organic carbon (DOC), on the control of Legionella by Cu-Ag ionization. Initial concentrations of Legionella and copper and silver ions used in batch experiments were 3 × 10 6 CFU/ml and 0.4 and 0.08 mg/liter, respectively. Changes in bicarbonate ion concentration (50, 100, and 150 mg/liter), water hardness (Ca 2+ at 50 and 100 mg/liter; Mg 2+ at 40 and 80 mg/liter), and level of DOC (0.5 and 2 mg/liter) had no significant impact on the efficacy of copper and silver ions in killing Legionella at a neutral pH. When the pH was elevated to 9 in these experiments, copper ions achieved only a 10-fold reduction in the number of Legionella organisms in 24 h, compared to a millionfold decrease at pH 7.0. Silver ions were able to achieve a millionfold reduction in 24 h at all ranges of water quality parameters tested. Precipitation of insoluble copper complexes was observed at a pH above 6.0. These results suggest that pH may be an important factor in the efficacy of copper-silver ionization in controlling Legionella in water systems.

Environmental monitoring of water systems for Legionella is performed for routine microbiological surveillance and outbreak investigations. The recovery of Legionella from water samples using conventional culture on selective media can be improved by sample concentration and/or sample decontamination techniques, but there is a reduction in recovery associated with these processes. A new immunoseparation method has been developed to improve the recovery of Legionella by concentrating and selectively separating Legionella spp. directly from water samples using immunomagnetic separation (IMS). Immunomagnetic separation has been used successfully for detection of other pathogens including Salmonella spp. The authors conducted the study in two phases and evaluated the IMS process alone and in combination with concentration and/or acid pretreatment in detecting Legionella spp. and Legionella pneumophila serogroup 1 (sg 1). The IMS procedure was performed using the BeadRetriever apparatus (Dynal Biotech Ltd., Preston, United Kingdom) for automated IMS using Dynabeads anti-Legionella (Dynal Biotech Ltd.). With the 11 known potable water samples, there was concordance (100% sensitivity) of culture results between the two methods, regardless of concentration or pretreatment of samples. The unconcentrated, untreated samples showed the greatest agreement in CFU/ml. Compared to conventional culture for L. pneumophila sg 1 only, the IMS method demonstrated a specificity of 98.5% (65 were negative and 2 were false-positive).