CONTEXT.—: Two major categories of laboratories performing nonwaived testing under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) are the Certificate of Accreditation (CoA) and Certificate of Compliance (CoC) laboratories. Accreditation organizations collect more detailed laboratory personnel information than the Centers for Medicare & Medicaid Services (CMS) Quality Improvement and Evaluation System (QIES). OBJECTIVE.—: To estimate total numbers of testing personnel and testing volumes in CoA and CoC laboratories, by laboratory type and state. DESIGN.—: We developed a statistical inference method by using the respective correlations between testing personnel counts and test volume by laboratory type. RESULTS.—: QIES reported 33 033 active CoA and CoC laboratories in July 2021. We estimated testing personnel to be 328 000 (95% CI, 309 000-348 000), which is supported by the count of 318 780 reported by the US Bureau of Labor Statistics. There were twice as many testing personnel in hospital laboratories as in independent laboratories (158 778 versus 74 904, P < .001). Independent laboratories had the highest test volume per person, which was twice as high as physician office laboratories (62 228 versus 30 102, P < .001). Hospital and independent laboratories comprised 34% of all CoA and CoC laboratories but performed the largest portion of testing (81%). Physician office laboratories, accounting for 44% of all CoA and CoC laboratories, performed a comparatively low proportion of total tests (9%). CONCLUSIONS.—: Numbers of testing personnel vary considerably by laboratory type and across states. These data can provide valuable insight when assessing laboratory workforce training needs and planning for public health emergencies.

BACKGROUND: Discrimination is a major driver of health disparities among minority groups and can impede the reach of public health programs. In the Dominican Republic, residents of bateyes, or agricultural 'company towns,' often face barriers to health care. This study examined the extent of perceived discrimination among batey populations and places the findings within the context of disease elimination efforts. METHODS: In March-April 2016, a stratified, multi-stage cluster survey that included the 9-item Everyday Discrimination Scale (EDS) was conducted among residents (n = 768) of bateyes across the Dominican Republic. Exploratory factor analysis, differential item functioning, and linear and logistic regression were used to assess associations between EDS scores, ethnic group status, reasons for discrimination, and healthcare-seeking behavior. RESULTS: Three ethnic groups were identified in the population: Haitian-born persons (42.5%), Dominican-born persons with Haitian descent (25.5%), and Dominican-born persons without Haitian descent (32.0%). Mean EDS scores (range 0-45) were highest among persons born in Haiti (18.2, 95% confidence interval [CI] = 16.4-20.1), followed by persons with Haitian descent (16.5, 95% CI = 14.9-18.0), and those without Haitian descent (13.3, 95% CI = 12.1-14.5). Higher EDS scores were significantly associated with Haitian birth (beta = 6.8, 95% CI = 4.2-9.4; p < 0.001) and Haitian descent (beta = 6.1, 95% CI = 3.2-9.0; p < 0.001). Most respondents (71.5%) had scores high enough to elicit reasons for their discrimination. Regardless of ethnic group, poverty was a common reason for discrimination, but Haitian-born and Haitian-descended people also attributed discrimination to their origin, documentation status, or skin color. EDS scores were not significantly associated with differences in reported care-seeking for recent fever (beta = 1.7, 95% CI = - 1.4-4.9; p = 0.278). CONCLUSION: Perceived discrimination is common among batey residents of all backgrounds but highest among Haitian-born people. Discrimination did not appear to be a primary barrier to care-seeking, suggesting other explanations for reduced care-seeking among Haitian populations. Public health community engagement strategies should avoid exacerbating stigma, build active participation in programs, and work towards community ownership of disease control and elimination goals.

Background: The burden and epidemiology of Mycoplasma pneumoniae (Mp) among U.S. children (<18 years) hospitalized with community-acquired pneumonia (CAP) are poorly understood. Methods: In the Etiology of Pneumonia in the Community (EPIC) study, we prospectively enrolled 2254 children hospitalized with radiographically-confirmed pneumonia from January 2010-June 2012 and tested nasopharyngeal/oropharyngeal swabs for Mp using real-time polymerase chain reaction (PCR). Clinical and epidemiological features of Mp-PCR-positive and -negative children were compared using logistic regression. Macrolide susceptibility was assessed by genotyping isolates. Results: In the EPIC study, 182(8%) children were Mp-PCR-positive (median age: 7 years); 12% required intensive care and 26% had pleural effusion. No in-hospital deaths occurred. Macrolide resistance was found in 6/169(4%) isolates. Of 178(98%) Mp-PCR-positive children tested for co-pathogens, 50(28%) had >/=1 co-pathogen detected. Variables significantly associated with higher odds of Mp detection included age {10-17 years [adjusted odds ratio (aOR): 7.9 (95% confidence interval (CI): 4.5-13.6)] and 5-9 years [aOR: 4.8 (CI: 2.9-7.8)] vs. 2-4 years}, outpatient antibiotics </=5 days pre-admission [aOR: 2.3 (CI: 1.5-3.4)], and co-pathogen detection [aOR: 2.1 (CI: 1.3-3.1)]. Clinical characteristics often seen included hilar lymphadenopathy, rales, headache, sore throat, and decreased breath sounds. Conclusions: Usually considered as a mild respiratory infection, M. pneumoniae was the most commonly detected bacteria among children >/=5 years hospitalized with CAP; one-quarter of whom had co-detections. Although associated with clinically non-specific symptoms, there was a need for intensive care support in some cases. M. pneumoniae should be included in the differential diagnosis for school-aged children hospitalized with CAP.

Background: Specimen labeling errors have long plagued the laboratory industry putting patients at risk of transfusion-related death, medication errors, misdiagnosis, and patient mismanagement. Many interventions have been implemented and deemed to be effective in reducing sample error rates. The objective of this review was to identify and evaluate the effectiveness of laboratory practices/ interventions to develop evidence based recommendations for the best laboratory practices to reduce labeling errors. Content: The standardized LMBP A-6 methods were used to conduct this systematic review. Total evidence included 12 studies published during the time periods of 1980 to September 2015. Combined data from seven studies found that the interventions developed as a result of improved communication and collaboration between the laboratory and clinical staff resulted in substantial decrease in specimen labeling errors (Median relative percent change in labeling errors: -75.86; IQI: -84.77, -58.00). Further data from subset of four studies showed a significant decrease in specimen labeling errors after the institution of the standardized specimen labeling protocols (Median relative percent decrease in specimen labeling errors: -72.45; IQI: -83.25, -46.50). Summary: Based on the evidence included in this review, the interventions that enhance the communication and collaboration between laboratory and healthcare professionals can decrease the specimen identification errors in healthcare settings. However, more research is needed to make the conclusion on the effectiveness of other evaluated practices in this review including training and education of the specimen collection staff, audit and feedback of labeling errors, and implementation of new technology (other than barcoding).

BACKGROUND: Using antibiotics appropriately is critical to slow spread of antibiotic resistance, a major public health problem. Children, especially young children, receive more antibiotics than other age groups. Our objective was to describe antibiotic use in children in the United States (US) and use of azithromycin, which is recommended infrequently for pediatric conditions. METHODS: We used QuintilesIMS Xponent 2013 data to calculate the number and rate of oral antibiotic prescriptions for children by age (0-2, 3-9 and 10-19 years) and agent. We used log-binomial regression to calculate adjusted prevalence rations (PR) and 95% confidence intervals (CI) to determine if specialty and patient age were associated with azithromycin selection when an antibiotic was prescribed. RESULTS: In 2013, 66.8 million antibiotics were prescribed to US children aged ≤19 years (813 antibiotic prescriptions per 1000 children). Amoxicillin and azithromycin were the two most commonly prescribed agents (23.1 million courses, 35% of all antibiotics; 12.2 million, 18%; respectively). Most antibiotics for children were prescribed by pediatricians (39%) and family practitioners (15%). Family practitioners were more likely to select azithromycin when an antibiotic was prescribed in all age groups than pediatricians (for children aged 0-2 years: PR 1.79, 95% CI, 1.78-1.80; 3-9 years: 1.40, 1.40-1.40; and 10-19 years: 1.18, 1.18-1.18). CONCLUSION: Despite infrequent pediatric recommendations, variations in pediatric azithromycin use may suggest inappropriate antibiotic selection. Public health interventions focused on improving antibiotic selection in children as well as reducing antibiotic overuse are needed.

BACKGROUND: We assessed the validity of testing for antimicrobial susceptibility of clinical and mutant Neisseria gonorrhoeae (GC) isolates by disk diffusion in comparison to agar dilution, and Etest(R) (bioMerieux, France), respectively, for three third generation extended spectrum cephalosporins (ESC): ceftriaxone (CRO), cefixime (CFX), and cefpodoxime (CPD). METHODS: One hundred and five clinical isolates and ten laboratory-mutants were tested following Clinical Laboratory Standard Institute (CLSI) and manufacturer's standards for each of the three methods. The measured diameters by the disk diffusion method were tested for correlation with the MIC values by agar dilution. In addition, comparisons with the Etest(R) were made. Categorical results for concordance, based on standard CLSI cutoffs, between the disk diffusion and the other two methods, respectively, were tested using the Chi-square statistics. Reproducibility was tested for CFX across a 6-month interval by repeated disk tests. RESULTS: Across all 115 specimens, the disk diffusion tests produced good categorical agreements, exhibiting concordance of 93.1%, 92.1%, and 90.4% with agar dilution and 93.0%, 92.1%, and 90.4% with Etest(R), for CRO, CFX, and CPD, respectively. Pearson correlations between disk-diffusion diameters and agar dilution MIC's were -0.59, -0.67, and -0.81 for CRO, CFX, and CPD, respectively. The correlations between disk diffusion and Etest(R) were -0.58, -0.73, and -0.49. Pearson correlation between the CFX disk readings over a 6-month interval was 91%. CONCLUSIONS: Disk diffusion tests remain to be a useful, reliable and fast screening method for qualitative antimicrobial susceptibility testing for ceftriaxone, cefixime, and cefpodoxime.

OBJECTIVE: This study was conducted to evaluate the responses of 3,265 health professionals who took a continuing education (CE) activity during June 2009 - April 2012 for a comprehensive set of good laboratory practice recommendations for molecular genetic testing. DESIGN: Participants completed an evaluation questionnaire as part of the CE activity. Responses were summarized to assess the participants' learning outcomes and commitment to applying the knowledge gained. PARTICIPANTS: Participants included nurses (47%), laboratory professionals (18%), physicians (14%), health educators (4%), public health professionals (2%), office staff (1%), and other health professionals (10%). RESULTS: Only 32% of all participants correctly answered all 12 open-book knowledge-check questions, ranging from 4 to 42% among the different professional groups (P<0.0001). However, over 80% of all participants expressed confidence in describing the practice recommendations, and 75% indicated the recommendations would improve the quality of their practice. Developing health education materials and local practice guidelines represented the common areas in which participants planned to use the knowledge gained (49% and 18% of all participants, respectively). CONCLUSION: Despite perceived self-efficacy in most participants, as high as 68% did not fully use the learning materials provided to answer the knowledge-check questions. These findings suggest the need for improved CE activities that motivate effective learning and address the specific needs of different health professions.

Neisseria meningitidis (Nm), Haemophilus influenzae (Hi), and Streptococcus pneumoniae (Sp) are the lead causes of bacterial meningitis. Detection of these pathogens from clinical specimens using traditional real-time PCR (rt-PCR) requires DNA extraction to remove the PCR inhibitors prior to testing, which is time consuming and labor intensive. In this study, five species-specific (Nm-sodC and -ctrA, Hi-hpd#1 and -hpd#3 and Sp-lytA) and six serogroup-specific rt-PCR tests (A, B, C, W, X, Y) targeting Nm capsular genes were evaluated in the two direct rt-PCR methods using PerfeCTa and 5x Omni that do not require DNA extraction. The sensitivity and specify of the two direct rt-PCR methods were compared to TaqMan traditional rt-PCR, the current standard rt-PCR method for the detection of meningitis pathogens. The LLD for all 11 rt-PCR tests ranged from 6,227 to 272,229 CFU/ml for TaqMan, 1,824-135,982 for 5x Omni, and 168-6,836 CFU/ml for PerfeCTa. The diagnostic sensitivity using TaqMan ranged from 89.2%-99.6%, except for NmB-csb, which was 69.7%. For 5x Omni, the sensitivity varied from 67.1% to 99.8%, with three tests below 90%. The sensitivity of these tests using PerfeCTa varied from 89.4% to 99.8%. The specificity ranges of the 11 tests were 98.0-99.9%, 97.5-99.9%, and 92.9-99.9% for TaqMan, 5x Omni, and PerfeCTa, respectively. PerfeCTa direct rt-PCR demonstrated similar or better sensitivity compared to 5x Omni direct rt-PCR or TaqMan traditional rt-PCR. Since the direct rt-PCR method does not require DNA extraction, it reduces the time and cost for processing CSF specimens, increases testing throughput, decreases the risk of cross-contamination, and conserves precious CSF. The direct rt-PCR method will be beneficial to laboratories with high testing volume.

BACKGROUND: Antimicrobial treatment and chemoprophylaxis of patients and their close contacts is critical to reduce the morbidity and mortality and prevent secondary cases of meningococcal disease. Through the 1990's, the prevalence of antimicrobial resistance to commonly used antimicrobials among Neisseria meningitidis was low in the United States. Susceptibility testing was performed to ascertain whether the proportions of isolates with reduced susceptibility to antimicrobials commonly used for N meningitidis have increased since 2004 in the United States. METHODS: Antimicrobial susceptibility testing was performed by broth microdilution on 466 isolates of N meningitidis collected in 2004, 2008, 2010, and 2011 from an active, population-based surveillance system for susceptibility to ceftriaxone, ciprofloxacin, penicillin G, rifampin, and azithromycin. The molecular mechanism of reduced susceptibility was investigated for isolates with intermediate or resistant phenotypes. RESULTS: All isolates were susceptible to ceftriaxone and azithromycin, 10.3% were penicillin G intermediate (range, 8% in 2008-16.7% in 2010), and <1% were ciprofloxacin, rifampin, or penicillin G resistant. Of the penicillin G intermediate or resistant isolates, 63% contained mutations in the penA gene associated with reduced susceptibility to penicillin G. All ciprofloxacin-resistant isolates contained mutations in the gyrA gene associated with reduced susceptibility. CONCLUSIONS:. Resistance of N meningitidis to antimicrobials used for empirical treatment of meningitis in the United States has not been detected, and resistance to penicillin G and chemoprophylaxis agents remains uncommon. Therapeutic agent recommendations remain valid. Although periodic surveillance is warranted to monitor trends in susceptibility, routine clinical testing may be of little use.

BACKGROUND: Appropriate antibiotic prescribing is an essential strategy to reduce the spread of antibiotic resistance. US prescribing practices have not been thoroughly characterized. We analyzed outpatient antibiotic prescribing data to identify where appropriate antibiotic prescribing interventions could have the most impact. METHODS: Oral antibiotic prescriptions dispensed during 2011 were extracted from the IMS Health Xponent database. The number of prescriptions and census denominators were used to calculate prescribing rates. Prescription totals were calculated for each provider specialty. Regression modeling was used to examine the association between socioeconomic and population health factors and prescribing rates. RESULTS: Healthcare providers prescribed 262.5 million courses of antibiotics in 2011(842 prescriptions per 1000 persons). Penicillins and macrolides were the most common antibiotic categories prescribed. The most commonly prescribed individual antibiotic agent was azithromycin. Family practitioners prescribed the most antibiotic courses (24%). The prescribing rate was higher in the South census region (931 prescriptions per 1000 persons) than in the West (647 prescriptions per 1000 persons; P < .001); this pattern was observed among all age groups, including children ≤2 and persons ≥65 years of age. Counties with a high proportion of obese persons, infants and children ≤2 years of age, prescribers per capita, and females were more likely to be high prescribing by multivariable analysis (adjusted odds ratio, >1.0). CONCLUSIONS: Efforts to characterize antibiotic prescribing practices should focus on the South census region and family practitioners. Further understanding of the factors leading to high prescribing among key target populations will inform appropriate prescribing interventions.

OBJECTIVES: To identify household-level factors associated with influenza among young children in a crowded community in Dhaka, Bangladesh. METHODS: We conducted a case-control study using existing active surveillance for respiratory illness. Cases were children aged 12-59 months with laboratory-confirmed influenza. Controls were children frequency-matched by age group with no respiratory illness in the prior six months. We interviewed caregivers and observed household handwashing behavior. Soap consumption was estimated by summing weight differences of three bars of soap sequentially left in each household. We measured concentrations of airborne particulate matter <2.5 mug in diameter (PM2.5 ) in a subset of households. We used logistic regression to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI). RESULTS: We enrolled 145 cases and 341 controls between March 2009 and April 2010. Case and control household members were observed to wash hands with similar frequency during a five-hour period (mean, 0.64 events vs. 0.63, p=0.87), and similar daily soap consumption per capita (mean 2.92 grams vs. 2.93, p=0.92). Case households were more likely than controls to have crowded (≥4 persons) sleeping areas (aOR=1.67, CI: 1.06-2.63) and cross-ventilated cooking spaces (aOR=1.75, CI: 1.16-2.63). Case and control households had similar median 24-hour geometric mean PM2.5 concentrations in the cooking (69.2 vs. 69.6 mcg/m3 , p=0.45) and sleeping (65.4 vs. 67.4 mcg/m3 , p=0.19) spaces. CONCLUSIONS: Handwashing with soap was practiced infrequently, and was not associated with pediatric influenza in this community. Interventions aimed at crowded households may reduce influenza incidence in young children.

BACKGROUND: In 2000, seven-valent pneumococcal conjugate vaccine (PCV7) was introduced in the USA and resulted in dramatic reductions in invasive pneumococcal disease (IPD) and moderate increases in non-PCV7 type IPD. In 2010, PCV13 replaced PCV7 in the US immunisation schedule. We aimed to assess the effect of use of PCV13 in children on IPD in children and adults in the USA. METHODS: We used laboratory-based and population-based data on incidence of IPD from the Active Bacterial Core surveillance (part of the Centers for Disease Control and Prevention's Emerging Infections Program) in a time-series model to compare rates of IPD before and after the introduction of PCV13. Cases of IPD between July 1, 2004, and June 30, 2013, were classified as being caused by the PCV13 serotypes against which PCV7 has no effect (PCV13 minus PCV7). In a time-series model, we used an expected outcomes approach to compare the reported incidence of IPD to that which would have been expected if PCV13 had not replaced PCV7. FINDINGS: Compared with incidence expected among children younger than 5 years if PCV7 alone had been continued, incidence of IPD overall declined by 64% (95% interval estimate [95% IE] 59-68) and IPD caused by PCV13 minus PCV7 serotypes declined by 93% (91-94), by July, 2012, to June, 2013. Among adults, incidence of IPD overall also declined by 12-32% and IPD caused by PCV13 minus PCV7 type IPD declined by 58-72%, depending on age. We estimated that over 30 000 cases of IPD and 3000 deaths were averted in the first 3 years after the introduction of PCV13. INTERPRETATION: PCV13 reduced IPD across all age groups when used routinely in children in the USA. These findings provide reassurance that, similar to PCV7, PCVs with additional serotypes can also prevent transmission to unvaccinated populations. FUNDING: Centers for Disease Control and Prevention.

Real-time (rt-) PCR is an important diagnostic tool for identification of Bordetella pertussis, B. holmesii, and B. parapertussis. Most United States public health laboratories (USPHLs) target IS481, present in 218-238 copies in the B. pertussis genome, and 32-65 copies in B. holmesii. CDC developed a multi-target PCR assay to differentiate B. pertussis, B. holmesii, and B. parapertussis, and provided protocols and training to 19 USPHLs. The 2012 performance exercise (PE) assessed the capability of USPHLs to detect these three Bordetella species in clinical samples. Laboratories were recruited by the Wisconsin State Proficiency Testing program through the Association of Public Health Laboratories, in partnership with CDC. Spring and Fall PE panels contained 12 samples each of viable Bordetella and non-Bordetella species in saline. Fifty and 53 USPHLs participated in the spring and fall PEs, respectively, using a variety of nucleic acid extraction methods, PCR platforms, and assays. Ninety-six percent and 94% of laboratories targeted IS481 in spring and fall, respectively, either in singleplex or multiplex assays. Seventy two percent and 79% of USPHLs could differentiate B. pertussis and B. holmesii in spring and fall, respectively; 68% and 72% could identify B. parapertussis. IS481 cycle threshold (Ct) values for B. pertussis samples had coefficients of variation (CV) ranging from 10% to 28%. Of the USPHLs who differentiated B. pertussis and B. holmesii, sensitivity and specificity was 96% and 95%, respectively, for the combined panels. The 2012 PEs demonstrated increased harmonization of rt-PCR Bordetella diagnostic protocols in USPHLs compared to the previous survey.

We studied whether the Etest can be used as an alternative to agar dilution to determine antimicrobial susceptibilities of ceftriaxone, cefixime, and cefpodoxime in Neisseria gonorrhoeae surveillance. One hundred fifteen clinical and laboratory isolates of N. gonorrhoeae were tested following the Clinical Laboratory Improvement Amendments (CLIA)-approved CLSI standard agar dilution method and, separately, by the Etest according to the manufacturer's recommendations. The MICs were determined and compared. Ten laboratory-generated mutants were used to simulate substantially nonsusceptible specimens. The Etest and agar dilution methods were well correlated. Statistical tests produced regression R(2) values of 88%, 82%, and 85% and Pearson correlation coefficients of 92%, 91%, and 92% for ceftriaxone, cefixime, and cefpodoxime, respectively. When paired comparisons were made, the two tests were 88.7%, 80%, and 87% within 1 log2 dilution from each other for ceftriaxone, cefixime, and cefpodoxime, respectively. The within-2-log2 agreements were 99.1%, 98.3%, and 94.8% for ceftriaxone, cefixime, and cefpodoxime, respectively. Notwithstanding the good correlations and the within-2-log2 general agreement, the Etest results produced slightly lower MICs than the agar dilution results. In conclusion, we found that the Etest can be effectively used as an alternative to agar dilution testing to determine the susceptibility of N. gonorrhoeae to ceftriaxone, cefixime, and cefpodoxime, although we recommend further research into extremely resistant isolates. For isolates within the typical range of clinical MICs, reexamination of the Etest interpretation of susceptible and nonsusceptible categories would likely allow for successful transition from agar dilution to the Etest.

Antibiotic-resistant bacteria are an increasing threat to the effectiveness of antibiotics. The majority of antibiotics are prescribed in primary care settings for upper respiratory tract infections. The purpose of this study was to describe seasonal trends in outpatient antibiotic prescriptions (Rx) in the United States over a 5-year period. This study was a retrospective, cross-sectional observation of systemic antibiotic prescriptions in the outpatient setting from 2006 to 2010. Winter months were defined as the first and fourth quarters of the calendar year. Antibiotic prescribing rates were calculated (prescriptions/1,000 population) using annual U.S. Census Bureau population data. Over 1.34 billion antibiotic prescriptions were dispensed over the 5-year period. The antibiotic prescription (Rx) rate decreased from 892 Rx/1,000 population in 2006 to 867 Rx/1,000 population in 2010. Penicillins and macrolides were the primary antibiotic classes prescribed, but penicillin prescribing decreased while macrolide prescribing increased over the study period. Overall, antibiotic prescriptions were 24.5% higher in winter months than in the summer, with the largest difference (28.8%) in 2008 and the smallest (20.4%) in 2010. This seasonality was consistently drug class dependent, driven by 75% and 100% increases in penicillin and macrolide prescriptions, respectively, in the winter months. The mean outpatient antibiotic prescription rate decreased in the United States from 2006 to 2010. More antibiotic prescribing, predominately driven by the macrolide and penicillin classes, in the outpatient setting was observed in the winter months. Understanding annual variability in antibiotic use can assist with designing interventions to improve the judicious use of antibiotics.

Since the establishment of sequence-based typing as the gold standard for DNA-based typing of Legionella pneumophila, the Centers for Disease Control and Prevention's (CDC) Legionella laboratory has conducted routine SBT analysis of all incoming L. pneumophila serogroup 1 (Lp1) isolates to identify potential links between cases and to better understand genetic diversity and clonal expansion among L. pneumophila. Retrospective genotyping of Lp1 isolates from sporadic cases and Legionnaires' disease (LD) outbreaks deposited into the CDC reference collection since 1982 has been completed. For this study, we compared the distribution of sequence types (STs) among Lp1 isolates implicated in 26 US outbreaks, 571 clinical isolates from US sporadic cases of LD and 149 environmental isolates with no known association with LD. The Lp1 isolates under study had been deposited into our collection between 1982 and 2012. We identified 17 outbreak-associated, 153 sporadic, and 49 environmental STs. We observed that Lp1 STs from outbreaks and sporadic cases are more similar to each other than either group is to environmental STs. The most frequent ST for both sporadic and environmental isolates was ST1, accounting for 25% and 49% of the total number of isolates, respectively. The STs shared by both outbreak-associated and sporadic Lp1 included ST1, ST35, ST36, ST37, and ST222. The STs most commonly found in sporadic and outbreak-associated Lp1 populations may have an increased ability to cause disease and thus may require special attention when detected.

Antibiotic use is an important factor in the spread of antibiotic resistance. It is estimated that 50% of antibiotic prescriptions may be unnecessary.1,2 We analyzed data on the prescription of antibiotics to outpatients in the United States to identify the areas in which interventions addressing appropriate use could have the greatest effect. | Data on oral antibiotic prescriptions dispensed during 2010 in the United States were extracted from the IMS Health Xponent database, which represents a 100% projection of prescription activity on the basis of a sample of more than 70% of U.S. prescriptions. Antibiotics were categorized according to the IMS Health Uniform System of Classification. The numbers of prescriptions and census denominators were used to calculate prescribing rates. Prescriptions were totaled for 17 provider specialty groups on the basis of the self-designated specialty of the prescriber (as defined by the American Medical Association) associated with each prescription. The Xponent database provided the number of prescribers in each specialty for the calculation of the number of prescriptions per provider.

In estimates of illness severity from the spring wave of the 2009 influenza A (H1N1) pandemic, reported case fatality proportions were less than 0.05%. In prior pandemics, subsequent waves of illness were associated with higher mortality. The authors evaluated the burden of the pandemic H1N1 (pH1N1) outbreak in metropolitan Atlanta, Georgia, in the fall of 2009, when increased influenza activity heralded the second wave of the pandemic in the United States. Using data from a community survey, existing surveillance systems, public health laboratories, and local hospitals, they estimated numbers of pH1N1-associated illnesses, emergency department (ED) visits, hospitalizations, intensive care unit (ICU) admissions, and deaths occurring in metropolitan Atlanta during the period August 16, 2009-September 26, 2009. The authors estimated 132,140 pediatric and 132,110 adult symptomatic cases of pH1N1 in metropolitan Atlanta during the investigation time frame. Among children, these cases were associated with 4,560 ED visits, 190 hospitalizations, 51 ICU admissions, and 4 deaths. Among adults, they were associated with 1,130 ED visits, 590 hospitalizations, 140 ICU admissions, and 63 deaths. The combined symptomatic case hospitalization proportion, case ICU admission proportion, and case fatality proportion were 0.281%, 0.069%, and 0.024%, respectively. Influenza burden can be estimated using existing data and local surveys. The increased severity reported for subsequent waves in past pandemics was not evident in this investigation. Nevertheless, the second pH1N1 pandemic wave led to substantial numbers of ED visits, hospitalizations, and deaths in metropolitan Atlanta.

We present a statistical summary of results from the Model Performance Evaluation Program (MPEP) for Mycobacterium tuberculosis Drug Susceptibility Testing, 1994-2008 implemented by the U.S. Centers for Disease Control and Prevention (CDC). During that period, a total of 57,733 test results for culture isolates were reported by 216 participating laboratories for the first-line anti-tuberculosis drugs used in the United States- isoniazid (INH), rifampin (RMP), ethambutol (EMB), and pyrazinamide (PZA). Using Clinical Laboratory and Standards Institute (CLSI) recommended concentrations for one or more of three methods, agar proportion (AP), BACTEC460 (BACTEC), and MGIT-960 (MGIT), yielded overall agreement of 97.0% for first-line drugs. For susceptible strains, agreement was 98.4%; for resistant strains, agreement was 91.0%, with significantly lower accuracy (Chi-sq p<0.0001). For resistant strains, overall agreement by methods was: AP 91.3%; BACTEC 93.0%; and MGIT 82.6% and by drugs was: INH 92.2%; RMP 91.5%; EMB 79.0%; and PZA 97.5%. For some strains, performance by method varied significantly. Use of duplicate strains in the same shipment and repeat strains over time, revealed consistent performance even for strains with higher levels of inter-laboratory discordance. No overall differences in performance between laboratories were observed based on volume of testing or type of facility (e.g., health department, hospital, independent). By all methods, decreased performance was observed for strains with low-level INH resistance, RMP resistance, and EMB-resistant strains. These results demonstrate a high level of performance in detection of drug resistant M. tuberculosis in U.S. laboratories.

BACKGROUND: Streptococcus pneumoniae infections have become increasingly complicated and costly to treat with the spread of antibiotic resistance. We evaluated the relationship between antibiotic prescribing and nonsusceptibility among invasive pneumococcal disease (IPD) isolates. METHODS: Outpatient antibiotic prescription data for penicillins, cephalosporins, macrolides, and trimethoprim-sulfamethoxazole were abstracted from the IMS Health Xponent database to calculate the annual number of prescriptions per capita. We analyzed IPD data from 7 of the Centers for Disease Control and Prevention's Active Bacterial Core surveillance sites (population, 18.6 million) for which data were available for the entire time period under study (1996-2003). Logistic regression models were used to assess whether sites with high antibiotic prescribing rates had a high proportion of nonsusceptible and serotype 19A IPD. RESULTS: Yearly prescribing rates during the period 1996-2003 for children <5 years of age decreased by 37%, from 4.23 to 2.68 prescriptions per capita per year (P < .001), and those for persons ≥5 years of age decreased by 42%, from 0.98 to 0.57 prescriptions per capita per year (P < .001); increases in azithromycin prescribing were noted for both groups. Sites with high rates of antibiotic prescribing had a higher proportion of IPD nonsusceptibility than did low-prescribing sites (P = .003 for penicillin, P < .001 for every other antibiotic class). Cephalosporin and macrolide prescribing were associated with penicillin and multidrug nonsusceptibility and serotype 19A IPD (P < .001). CONCLUSIONS: In sites where antibiotic prescribing is high, the proportion of nonsusceptible IPD is also high, suggesting that local prescribing practices contribute to local resistance patterns. Cephalosporins and macrolides seem to be selecting for penicillin- and multidrug-resistant pneumococci, as well as serotype 19A IPD. Antibiotic use is a major factor contributing to the spread of antibiotic resistance; strategies to reduce antibiotic resistance should continue to include judicious use of antibiotics. (See the Editorial Commentary by Huttner and Samore, on pages 640-643.)

From April 2009 through March 2010, during the pandemic (H1N1) 2009 outbreak, approximately 8.2 million prescriptions for influenza neuraminidase-inhibiting antiviral drugs were filled in the United States. We estimated the number of hospitalizations likely averted due to use of these antiviral medications. After adjusting for prescriptions that were used for prophylaxis and personal stockpiles, as well as for patients who did not complete their drug regimen, we estimated the filled prescriptions prevented approximately 8,400-12,600 hospitalizations (on the basis of median values). Approximately 60% of these prevented hospitalizations were among adults 18-64 years of age, with the remainder almost equally divided between children 0-17 years of age and adults >65 years of age. Public health officials should consider these estimates an indication of success of treating patients during the 2009 pandemic and a warning of the need for renewed planning to cope with the next pandemic.

BACKGROUND: The epidemiology of streptococcal infection in pregnant and postpartum women is poorly described in recent literature. We used data from multistate surveillance for invasive Streptococcus pneumoniae, group A Streptococcus (GAS), and group B Streptococcus (GBS) infections to estimate disease incidence and severity in these populations. METHODS: Cases were reported through the Centers for Disease Control and Prevention Active Bacterial Core surveillance, an active population- and laboratory-based system. A case was defined as illness in a woman aged 15-44 years with streptococcus isolated from a normally sterile body site during 2007-2009. Pregnant or postpartum status was recorded at the time of culture. Incidence was calculated as cases per 1000 woman-years with use of national Census data; 95% confidence intervals were calculated on the basis of lambda distribution. We used multivariable logistic regression to explore associations between pregnant or postpartum status and hospital length of stay, a marker of disease severity. RESULTS: We identified 1848 cases in women; 6.0% of women were pregnant, and 7.5% were postpartum. Pregnant women had a higher mean incidence of GBS disease, compared with nonpregnant women (0.04 cases per 1000 woman-years [range, 0.03-0.05 cases per 1000 woman-years] vs 0.02 cases per 1000 woman-years [range, 0.02-0.02 cases per 1000 woman-years]). Postpartum women had elevated mean incidence of all 3 pathogens, compared with nonpregnant women (S. pneumoniae: 0.15 cases per 1000 woman-years [range, 0.09-0.25 cases per 1000 woman-years] vs 0.052 cases per 1000 woman-years [range, 0.049-0.056 cases per 1000 woman-years]; GAS: 0.56 cases per 1000 woman-years [range, 0.42-0.70 cases per 1000 woman-years] vs 0.019 cases per 1000 woman-years [range, 0.017-0.021 cases per 1000 woman-years]; GBS: 0.49 cases per 1000 woman-years [range, 0.36-0.64 cases per 1000 woman-years] vs 0.018 [range, 0.016-0.020 cases per 1000 woman-years]). Neither pregnancy nor postpartum status was associated with longer length of stay among women infected with any of the 3 pathogens. CONCLUSIONS: Although invasive streptococcal infections do not appear to be more severe in pregnant or postpartum women, postpartum women have a 20-fold increased incidence of GAS and GBS, compared with nonpregnant women.

A pilot study for the Environmental Legionella Isolation Techniques Evaluation (ELITE) Program, a proficiency testing scheme for US laboratories that culture Legionella from environmental samples, was conducted September 1, 2008 through March 31, 2009. Participants (n=20) processed panels consisting of six sample types: pure and mixed positive, pure and mixed negative, pure and mixed variable. The majority (93%) of all samples (n=286) were correctly characterized, with 88.5% of samples positive for Legionella and 100% of negative samples identified correctly. Variable samples were incorrectly identified as negative in 36.9% of reports. For all samples reported positive (n=128), participants underestimated the cfu/ml by a mean of 1.25 logs with standard deviation of 0.78 logs, standard error of 0.07 logs, and a range of 3.57 logs compared to the CDC re-test value. Centering results around the interlaboratory mean yielded a standard deviation of 0.65 logs, standard error of 0.06 logs, and a range of 3.22 logs. Sampling protocol, treatment regimen, culture procedure, and laboratory experience did not significantly affect the accuracy or precision of reported concentrations. Qualitative and quantitative results from the ELITE pilot study were similar to reports from a corresponding proficiency testing scheme available in the European Union, indicating these results are probably valid for most environmental laboratories worldwide. The large enumeration error observed suggests that the need for remediation of a water system should not be determined solely by the concentration of Legionella observed in a sample since that value is likely to underestimate the true level of contamination.

The large and growing number of viral and bacterial pathogens responsible for respiratory infections poses a challenge for laboratories to provide rapid and comprehensive pathogen identification. We evaluated a novel application of the TaqMan(R) Low Density Array (TLDA) cards for real-time PCR detection of 21 respiratory pathogen targets. TLDA performance was compared to individual real-time PCR (IRTP) assays with the same primers and probes using 1) nucleic acids extracted from the 21 pathogen strains and 66 closely-related viruses and bacteria and 2) 292 clinical respiratory specimens. Using spiked samples, TLDA cards were about ten-fold less sensitive than the IRTP assays. Using 292 clinical specimens to generate 2238 paired individual assays, TLDA exhibited 89% sensitivity (95% confidence interval [CI] 86-92; 47-100 range per target) and 98% specificity (95% CI 97-99; 85-100 range per target) overall compared to IRTP real-time assays as the gold standard with a Ct cut-off of 43. The TLDA card approach offers promise for rapid and simultaneous identification of multiple respiratory pathogens for outbreak investigations and disease surveillance.

BACKGROUND: Severe illness due to 2009 pandemic A(H1N1) infection has been reported among persons who are obese or morbidly obese. We assessed whether obesity is a risk factor for hospitalization and death due to 2009 pandemic influenza A(H1N1), independent of chronic medical conditions considered by the Advisory Committee on Immunization Practices (ACIP) to increase the risk of influenza-related complications. METHODOLOGY/PRINCIPAL FINDINGS: We used a case-cohort design to compare cases of hospitalizations and deaths from 2009 pandemic A(H1N1) influenza occurring between April-July, 2009, with a cohort of the U.S. population estimated from the 2003-2006 National Health and Nutrition Examination Survey (NHANES); pregnant women and children <2 years old were excluded. For hospitalizations, we defined categories of relative weight by body mass index (BMI, kg/m(2)); for deaths, obesity or morbid obesity was recorded on medical charts, and death certificates. Odds ratio (OR) of being in each BMI category was determined; normal weight was the reference category. Overall, 361 hospitalizations and 233 deaths included information to determine BMI category and presence of ACIP-recognized medical conditions. Among >or=20 year olds, hospitalization was associated with being morbidly obese (BMI>or=40) for individuals with ACIP-recognized chronic conditions (OR = 4.9, 95% CI 2.4-9.9) and without ACIP-recognized chronic conditions (OR = 4.7, 95%CI 1.3-17.2). Among 2-19 year olds, hospitalization was associated with being underweight (BMI<or=5(th) percentile) among those with (OR = 12.5, 95%CI 3.4-45.5) and without (OR = 5.5, 95%CI 1.3-22.5) ACIP-recognized chronic conditions. Death was not associated with BMI category among individuals 2-19 years old. Among individuals aged >or=20 years without ACIP-recognized chronic medical conditions death was associated with obesity (OR = 3.1, 95%CI: 1.5-6.6) and morbid obesity (OR = 7.6, 95%CI 2.1-27.9). CONCLUSIONS/SIGNIFICANCE: Our findings support observations that morbid obesity may be associated with hospitalization and possibly death due to 2009 pandemic H1N1 infection. These complications could be prevented by early antiviral therapy and vaccination.

BACKGROUND: Animal models and data from influenza pandemics suggest that influenza infection predisposes individuals to pneumococcal pneumonia. Influenza may contribute to high winter rates of pneumococcal pneumonia during non-pandemic periods, but the magnitude of this effect is unknown. With use of United States surveillance data during 1995-2006, we estimated the association between influenza circulation and invasive pneumococcal pneumonia rates. METHODS: Weekly invasive pneumococcal pneumonia incidence, defined by isolation of pneumococci from normally sterile sites in persons with clinical or radiographic pneumonia, was estimated from active population-based surveillance in 3 regions of the United States. We used influenza virus data collected by World Health Organization collaborating laboratories in the same 3 regions in seasonally adjusted negative binomial regression models to estimate the influenza-associated fraction of pneumococcal pneumonia. RESULTS: During approximately 185 million person-years of surveillance, we observed 21,239 episodes of invasive pneumococcal pneumonia; 485,691 specimens were tested for influenza. Influenza circulation was associated with 11%-14% of pneumococcal pneumonia during periods of influenza circulation and 5%-6% overall. In 2 of 3 regions, the association was strongest when influenza circulation data were lagged by 1 week. CONCLUSIONS: During recent seasonal influenza epidemics in the United States, a modest but potentially preventable fraction of invasive pneumococcal pneumonia was associated with influenza circulation.

Rates of invasive pneumococcal disease in the United States increase dramatically, or “spike,” during winter holidays.1 We analyzed population-based surveillance data to determine whether spikes may be caused by increased transmission from children to older adults. | Pneumococci spread through upper respiratory secretions, especially those of young children.2 Certain serotypes disproportionately colonize young children.3 The introduction of the pediatric heptavalent pneumococcal conjugate vaccine (PCV7; Prevnar, Wyeth) in 2000 led to a decrease in invasive pneumococcal disease among vaccinated children and reduced transmission to unvaccinated persons.2,4

Approximately 84% of legionellosis cases are due to Legionella pneumophila serogroup 1. Moreover, a majority of L. pneumophila serogroup 1 clinical isolates react positively with monoclonal antibody 2 (MAb2) of the international standard panel. Over 94% of the legionellosis outbreaks investigated by the Centers for Disease Control and Prevention are due to this subset of L. pneumophila serogroup 1. To date, there is no complete explanation for the enhanced ability of these strains to cause disease. To better characterize these organisms, we subtyped 100 clinical L. pneumophila serogroup 1 isolates and 50 environmental L. pneumophila serogroup 1 isolates from the United States by (i) reactivity with MAb2, (ii) presence of a lag-1 gene required for the MAb2 epitope, and (iii) sequence-based typing analysis. Our results showed that the MAb2 epitope and lag-1 gene are overrepresented in clinical L. pneumophila serogroup 1 isolates. MAb2 recognized 75% of clinical isolates but only 6% of environmental isolates. Similarly, 75% of clinical isolates but only 8% of environmental isolates harbored lag-1. We identified three distinct lag-1 alleles, referred to as Philadelphia, Arizona, and Lens alleles, among 79 isolates carrying this gene. The Arizona allele is described for the first time in this study. We identified 59 different sequence types (STs), and 34 STs (58%) were unique to the United States. Our results support the hypothesis that a select group of STs may have an enhanced ability to cause legionellosis. Combining sequence typing and lag-1 analysis shows that STs tend to associate with a single lag-1 allele type, suggesting a hierarchy of virulence genotypes. Further analysis of ST and lag-1 profiles may identify genotypes of L. pneumophila serogroup 1 that warrant immediate intervention.