Controversies in tuberculous infection among pediatric infectious disease specialists in North America.

OBJECTIVE: To evaluate the extent to which advancements in the diagnosis and treatment of latent tuberculous infection (LTBI) have been integrated into practice by pediatric infectious disease (PID) specialists. DESIGN: We conducted an online survey of the Infectious Diseases Society of America's Emerging Infections Network (EIN) membership. RESULTS: Of the 323 members, 197 (61%) responded: 7% cared for ⩾5 children with TB disease and 34% for ⩾5 children with LTBI annually. We identified substantial variations in the use of interferon-gamma release assays (IGRAs) based upon age, immune status, and TB risk factors. In addition, tuberculin skin test (TST) use was three times more common in younger children. Variations existed in managing children with discordant TST and IGRA results. Less variation existed in LTBI treatment, with 86% preferring a 9-month course of isoniazid; few other, newer regimens were used routinely. CONCLUSION: Substantial variations exist in LTBI management; uptake of newer diagnostic tools and treatment regimens has been slow. Variations in practice and the lag time to integrating new data into practice may indicate the relative infrequency with which providers encounter LTBI. Our findings reflect the need for increased visibility of existing TB guidelines and resources for expert consultation for scenarios not covered by guidelines.

Communication gaps for solid organ transplant-transmitted infections among infectious disease physicians: an Emerging Infections Network survey.

Infectious disease (ID) physicians were surveyed concerning knowledge and management of potential transplant-transmitted infections (TTIs). On the basis of cumulative responses to 4 questions that assessed solid organ transplant-related clinical exposures and experience, respondents were divided into 3 groups: most, some, or little transplant experience. Rapid access to donor data was identified as the most important factor when evaluating a potential TTI. Despite varying experience in transplant infections, ID physicians are frequently asked for opinions regarding donor suitability and TTI management. Improved ID physician access to donor information and educational resources will allow more optimal management of potential TTIs.

Treatment patterns of pediatric nontuberculous mycobacterial (NTM) cervical lymphadenitis as reported by nationwide surveys of pediatric otolaryngology and infectious disease societies.

OBJECTIVE: To describe physician diagnostic and therapeutic strategies for pediatric nontuberculous mycobacterial (NTM) lymphadenitis, a disease for which surgical excision is recommended. METHODS: We surveyed members of the Infectious Diseases Society of America Emerging Infections Network (EIN) and the American Society of Pediatric Otolaryngology (ASPO). We asked them to report clinical and microbiologic details of recent cases of NTM lymphadenitis seen in their practices. RESULTS: 200 physicians reported a total of 277 NTM lymphadenitis cases. Cervical lymph nodes (84%) were most frequently involved, and a majority of patients were non-Hispanic white (62%) males (54%) with median age 3.0 years. Tissue culture (61%) or polymerase chain reaction (12%) was utilized most frequently to confirm NTM etiology. In most (59%) cases, an etiologic organism was not identified. In cases, where an NTM organism isolate was identified, Mycobacterium avium complex (n=82, 72%) was the most common. Surgical excision followed by adjunctive antibiotic therapy was favored in the majority (59%) of cases where a treatment method was reported. The use of surgical excision alone or antibiotic therapy alone was reported respectively in 24% and 17% of cases. Antibiotics were prescribed without diagnostic confirmation of infectious organisms in 28% of cases. CONCLUSION: Pediatric otolaryngologists and infectious disease specialists frequently treat cervical lymphadenitis empirically as NTM disease without bacteriologic confirmation. Antibiotic therapy is frequently employed with or without surgical excision.

Mycobacterial and other serious infections in patients receiving anti-tumor necrosis factor and other newly approved biologic therapies: case finding through the Emerging Infections Network.

We present the results of a nationwide survey of infectious disease consultants to identify mycobacterial and other serious infections in patients receiving anti-tumor necrosis factor compounds and other novel targeted therapies. Nontuberculous mycobacterial infections, histoplasmosis, and invasive Staphylococcus aureus infection were all reported more frequently than was tuberculosis disease in this context.

Antimicrobial use in Europe and antimicrobial resistance in Streptococcus pneumoniae.

The study presented here determined the relationship between antimicrobial resistance in Streptococcus pneumoniae and the use of antimicrobial agents in 15 different European countries. Pneumococcal isolates (n = 1974) recovered from patients with community-acquired respiratory tract infections during the winter of 2004-2005 in 15 European countries were characterized. The overall percentages of isolates demonstrating intermediate or complete resistance to penicillin, erythromycin, tetracycline, trimethoprim-sulfamethoxazole (TMP-SMX) and ciprofloxacin were 24, 24.6, 19.8, 26.7 and 2%, respectively, as determined using the broth microdilution MIC method recommended by the Clinical and Laboratory Standards Institute. The overall and mean antimicrobial consumption levels (ACL)--i.e., the defined daily doses per 1,000 inhabitants per day--were obtained from the European Surveillance of Antimicrobial Consumption project for each of the 15 countries for the years 1998-2004. Using linear regression analysis, the mean annual ACL for beta-lactams, macrolides, tetracyclines, TMP-SMX and fluoroquinolones in each country was compared to the country-specific resistance rates determined in 2004-2005. The rate of overall antimicrobial use in all 15 European countries was significantly associated with antimicrobial resistance in S. pneumoniae. There was variation among the different antimicrobial classes as drivers of resistance, with beta-lactams having the strongest association.

Macrolide use identified as risk factor for macrolide-resistant Streptococcus pneumoniae in a 17-center case-control study.

The objective of the case-control study presented here was to examine the risk factors for macrolide-resistant Streptococcus pneumoniae. As part of a 44-center U.S. surveillance study, 1,817 unique isolates of S. pneumoniae were collected from November 2002 through April 2003. Seventy-five randomly selected macrolide-resistant isolates (cases) were each matched with one susceptible control. Macrolide use in the 6 weeks prior to sample collection was reported for seven cases and one control. The final conditional logistic regression model identified two statistically significant variables: a history of alcohol abuse was protective, while macrolide use in the 6 weeks prior to sample collection was a significant risk factor for macrolide-resistant S. pneumoniae. Macrolide resistance was associated with use of any antibiotic during the prior 6 weeks, and was most strongly associated with previous macrolide use.

The molecular epidemiology of Streptococcus pneumoniae with quinolone resistance mutations.

BACKGROUND: The purpose of this study was to determine the prevalence of fluoroquinolone resistance and quinolone resistance-determining region (QRDR) mutations among Streptococcus pneumoniae isolates in the United States during the period of 2001-2002. A second objective was to examine the genetic relatedness of pneumococcal isolates with parC and/or gyrA mutations during the period of 1994-2002. METHODS: Susceptibility testing was performed for 1902 S. pneumoniae isolates collected in the United States during the period of 2001-2002. On the basis of the minimum inhibitory concentration (MIC) of ciprofloxacin, 146 isolates were selected from the 2001-2002 study for QRDR analysis of parC, parE, gyrA, and gyrB genes. The genetic relatedness of isolates with parC and/or gyrA mutations from 2001-2002 (n=55) and from 3 US surveillance studies conducted during 1994-2000 (n=56) was determined by pulsed-field gel electrophoresis (PFGE). RESULTS: Between 1999-2000 and 2001-2002, there was a 2-fold increase in the rate of ciprofloxacin resistance (MIC, >or=4 micro g/mL), from 1.2% to 2.7%, and in the rate of levofloxacin nonsusceptibility (MIC, >or=4 micro g/mL), from 0.6% to 1.3%. The 111 isolates with parC and/or gyrA mutations were assigned to 48 different PFGE types. Forty-four isolates (40%) belonged to 8 PFGE types that were closely related to widespread clones. Fifteen of the 43 levofloxacin-nonsusceptible pneumococci (LNSP) belonged to 4 PFGE types that were closely related to major clones (Spain(23F)-1 [n=6]; Spain(6B)-2 [n=5], Taiwan(19F)-14 [n=2], and Tennessee(23F)-4 [n=2]). CONCLUSION: The population of fluoroquinolone-resistant S. pneumoniae in the United States has increased but remains genetically diverse. However, 35% of LNSP were related to widespread pneumococcal clones, increasing the potential for the rapid spread of quinolone resistance in this species.

Epidemiology and outcome of nosocomial and community-onset bloodstream infection.

We performed a prospective study of bloodstream infection to determine factors independently associated with mortality. Between February 1999 and July 2000, 929 consecutive episodes of bloodstream infection at two tertiary care centers were studied. An ICD-9-based Charlson Index was used to adjust for underlying illness. Crude mortality was 24% (14% for community-onset versus 34% for nosocomial bloodstream infections). Mortality attributed to the bloodstream infection was 17% overall (10% for community-onset versus 23% for nosocomial bloodstream infections). Multivariate logistic regression revealed the independent associations with in-hospital mortality to be as follows: nosocomial acquisition (odds ratio [OR] 2.6, P < 0.0001), hypotension (OR 2.6, P < 0.0001), absence of a febrile response (P = 0.003), tachypnea (OR 1.9, P = 0.001), leukopenia or leukocytosis (total white blood cell count of <4500 or >20000, P = 0.003), presence of a central venous catheter (OR 2.0, P = 0.0002), and presence of anaerobic organism (OR 2.5, P = 0.04). Even after adjustments were made for underlying illness and length of stay, nosocomial status of bloodstream infection was strongly associated with increased total hospital charges (P < 0.0001). Although accounting for about half of all bloodstream infections, nosocomial bloodstream infections account for most of the mortality and costs associated with bloodstream infection.

Effects of rapid detection of bloodstream infections on length of hospitalization and hospital charges.

Current automated continuous-monitoring blood culture systems afford more rapid detection of bacteremia and fungemia than is possible with non-instrument-based manual methods. Use of these systems has not been studied objectively with respect to impact on patient outcomes, including hospital charges and length of hospitalization. We conducted a prospective, two-center study in which the time from the obtainment of the initial positive blood culture until the Gram stain was called was evaluated for 917 cases of bloodstream infection. Factors showing univariate associations with a shorter time to notification included higher body temperature and respiratory rate and higher percentage of immature neutrophils. Multiple linear regression models determined that the primary predictors of both increased microbiology laboratory and total hospital charges for patients with bloodstream infection were nonmicrobiologic and included length of stay and host factors such as the admitting service and underlying illness score. Significant microbiologic predictors of increased charges included the number of blood cultures obtained, nosocomial acquisition, and polymicrobial bloodstream infections. Accelerated failure time regression analysis demonstrated that microbiologic factors, including time until notification, organism group, and nosocomial acquisition, were independently associated with length of hospitalization after bacteremia, as were the factors of admitting service, gender, and age. Our data suggest that an increased time to notification of bloodstream infection is independently associated with increased length of stay. We conclude that the time to notification is an obvious target for efforts to shorten length of stay. The newest generation of automated continuous-monitoring blood culture systems, which shorten the time required to obtain a positive result, should impact length of hospitalization.

Minimizing the workup of blood culture contaminants: implementation and evaluation of a laboratory-based algorithm.

An algorithm was implemented in the clinical microbiology laboratory to assess the clinical significance of organisms that are often considered contaminants (coagulase-negative staphylococci, aerobic and anaerobic diphtheroids, Micrococcus spp., Bacillus spp., and viridans group streptococci) when isolated from blood cultures. From 25 August 1999 through 30 April 2000, 12,374 blood cultures were submitted to the University of Iowa Clinical Microbiology Laboratory. Potential contaminants were recovered from 495 of 1,040 positive blood cultures. If one or more additional blood cultures were obtained within +/-48 h and all were negative, the isolate was considered a contaminant. Antimicrobial susceptibility testing (AST) of these probable contaminants was not performed unless requested. If no additional blood cultures were submitted or there were additional positive blood cultures (within +/-48 h), a pathology resident gathered patient clinical information and made a judgment regarding the isolate's significance. To evaluate the accuracy of these algorithm-based assignments, a nurse epidemiologist in approximately 60% of the cases performed a retrospective chart review. Agreement between the findings of the retrospective chart review and the automatic classification of the isolates with additional negative blood cultures as probable contaminants occurred among 85.8% of 225 isolates. In response to physician requests, AST had been performed on 15 of the 32 isolates with additional negative cultures considered significant by retrospective chart review. Agreement of pathology resident assignment with the retrospective chart review occurred among 74.6% of 71 isolates. The laboratory-based algorithm provided an acceptably accurate means for assessing the clinical significance of potential contaminants recovered from blood cultures.

Hospital bloodborne pathogens programs: program characteristics and blood and body fluid exposure rates.

OBJECTIVE: To describe hospital practices and policies relating to bloodborne pathogens and current rates of occupational exposure among healthcare workers. PARTICIPANTS AND METHODS: Hospitals in Iowa and Virginia were surveyed in 1996 and 1997 about Standard Precautions training programs and compliance. The primary outcome measures were rates of percutaneous injuries and mucocutaneous exposures. RESULTS: 153 (64%) of 240 hospitals responded. New employee training was offered no more than twice per year by nearly one third. Most (79%-80%) facilities monitored compliance of nurses, housekeepers, and laboratory technicians; physicians rarely were trained or monitored. Implementation of needlestick prevention devices was the most common action taken to decrease sharps injuries. Over one half of hospitals used needleless intravenous systems; larger hospitals used these significantly more often. Protected devices for phlebotomy or intravenous placement were purchased by only one third. Most (89% of large and 80% of small) hospitals met the recommended infection control personnel-to-bed ratio of 1:250. Eleven percent did not have access to postexposure care during all working hours. Percutaneous injury surveillance relied on incident reports (99% of facilities) and employee health records (61%). The annual reported percutaneous injury incidence rate from 106 hospitals was 5.3 injuries per 100 personnel. Compared to single tertiary-referral institution rates determined more than 5 years previously, current injury rates remain elevated in community hospitals. CONCLUSIONS: Healthcare institutions need to commit sufficient resources to Standard Precautions training and monitoring and to infection control programs to meet the needs of all workers, including physicians. Healthcare workers clearly remain at risk for injury. Further effective interventions are needed for employee training, improving adherence, and providing needlestick prevention devices.

Monitoring adherence to Standard Precautions.

BACKGROUND: Health care workers (HCWs) do not consistently follow Standard Precautions (SP). This is a serious problem because inadequate compliance is associated with increased blood exposure thus predisposing HCWs to bloodborne pathogen transmission. METHODS: The primary goal of this study was to identify institutional factors associated with adequacy of HCW training to monitor coworkers' adherence to SP. Surveys were sent to all community hospital infection control practitioners (ICPs) in Iowa and Virginia. ICPs indicated on a 5-point Likert scale, ranging from strongly disagree to strongly agree, their assessment of HCW training adequacy. Data from another statewide survey of HCWs in Iowa were assessed to validate this outcome measure. Multiple logistic regression models were developed to identify predictors of assessed training adequacy. Independent variables included methods of education, training, approaches to SP compliance assessment, provision of SP reinforcement by clinical leaders, and organizational data. RESULTS: A total of 149 institutions (62%) participated. Models of training program adequacy varied across occupations. Management commitment to SP training programs, leadership support, frequency of providing bloodborne pathogen information, and safety climate were important institutional predictors of assessed adequacy of training. The outcome was validated by demonstrating an association between the ICPs' assessment of HCW training and workers who reported having sufficient information to comply with SP (P <.05). CONCLUSIONS: Institutional safety climate, leadership support, and frequency of education play an important role in HCWs' training adequacy to monitor coworkers' adherence to SP. Occupational groups should be considered independently when strategies are developed to increase compliance. Interventions based on modifiable factors identified by this study may reduce bloodborne pathogen exposure among HCWs.

Frontiers of occupational health. New vaccines, new prophylactic regimens, and management of the HIV-infected worker.

New prophylactic or treatment options are available for a number of infectious diseases that may be transmitted in the health care setting. Infectious diseases that can now be prevented by vaccination of the employee include hepatitis A, pertussis, hepatitis B, and primary varicella. New prophylactic or treatment regimens are available for Neisseria meningitidis, Streptococcus pyogenes, and Bordetella pertussis; treatment of multidrug-resistant tuberculosis is also discussed. Finally, management of the HIV-infected health care worker is reviewed.

Rapid identification of respiratory viruses: impact on isolation practices and transmission among immunocompromised pediatric patients.

OBJECTIVE: To determine whether empiric isolation of patients with acute respiratory virus infection symptoms could be discontinued when preliminary shell vial cultures were negative, and the impact of this approach on hospital resources. DESIGN: In 1993, we retrospectively reviewed respiratory virus test results from 1992 to 1993 and extended data collection prospectively through the 1993 to 1994 season. The rapid test and 48-hour shell vial results were compared to a standard of rapid test plus 5-day shell vial culture results to determine the sensitivity and specificity of these "preliminary" results. SETTING: A 400-bed tertiary referral research hospital. PATIENTS: Patients from any inpatient unit or clinic with acute respiratory virus infection symptoms who had a specimen submitted for respiratory virus culture. Patients were placed on empiric respiratory isolation pending culture results. RESULTS: The overall sensitivity of the combined rapid and 48-hour culture results in adults and children was 97%. All 15 pediatric patients with respiratory syncytial virus infection who had specimens submitted on first suspicion of respiratory virus infection were positive by rapid test. Culture results were positive within 48 hours for 100% of patients with influenza A (15 patients), influenza B (6), and parainfluenza (18) viruses. Of 59 pediatric inpatients who were isolated empirically awaiting 5-day culture results, 31 (52%) ultimately were determined to be culture negative. CONCLUSIONS: Empiric isolation of symptomatic children can be discontinued at 48 hours when both the rapid test and the early culture results are negative. Our institution would have saved 93 days of unnecessary isolation over 2 years had such a policy been in place.

Mycobacterial and fungal infections of bone and joints.

The number of cases of tuberculous bone or joint infection reported annually in the United States has been rising, but it decreased slightly in 1993. Management of skeletal tuberculosis is a complex and evolving issue that requires knowledge of the treatment of drug-resistant organisms. Nontuberculous mycobacteria also may cause skeletal infections, which are often located in tenosynovium or osteoarticular components of the hand or wrist but may occur at other skeletal sites, particularly when there is underlying immunosuppression. Identification of the organism and determination of its drug sensitivities are crucial for providing optimal therapy. Fungal infections of bone or joint can be difficult to treat, but the availability of fluconazole and itraconazole has extended our therapeutic options for some mycoses.

PCR amplification of rRNA intergenic spacer regions as a method for epidemiologic typing of Clostridium difficile.

From January to March 1993, a suspected outbreak of antibiotic-associated diarrhea occurred on a pediatric oncology ward of the Clinical Center Hospital at the National Institutes of Health. Isolates of Clostridium difficile obtained from six patients implicated in this outbreak were typed by both PCR amplification of rRNA intergenic spacer regions (PCR ribotyping) and restriction endonuclease analysis of genomic DNA. Comparable results were obtained with both methods; five of the six patients were infected with the same strain of C. difficile. Subsequent analysis of 102 C. difficile isolates obtained from symptomatic patients throughout the Clinical Center revealed the existence of 41 distinct and reproducible PCR ribotypes. These data suggest that PCR ribotyping provides a discriminatory, reproducible, and simple alternative to conventional molecular approaches for typing strains of C. difficile.

Managing occupational risks in the dental office: HIV and the dental professional.

Despite universal precautions, work behavior modifications and technological advances, health care workers continue to experience occupational exposures to HIV and other bloodborne pathogens. Although the risk for infection is low when compared with other bloodborne pathogens, 39 documented cases of HIV seroconversion have been recorded. Recent attention has focused on secondary prevention of HIV infection through post-exposure chemoprophylaxis.