Connie S. Price

Azithromycin for prevention of exacerbations of COPD.

BACKGROUND Acute exacerbations adversely affect patients with chronic obstructive pulmonary disease (COPD). Macrolide antibiotics benefit patients with a variety of inflammatory airway diseases. METHODS We performed a randomized trial to determine whether azithromycin decreased the frequency of exacerbations in participants with COPD who had an increased risk of exacerbations but no hearing impairment, resting tachycardia, or apparent risk of prolongation of the corrected QT interval. RESULTS A total of 1577 subjects were screened; 1142 (72%) were randomly assigned to receive azithromycin, at a dose of 250 mg daily (570 participants), or placebo (572 participants) for 1 year in addition to their usual care. The rate of 1-year follow-up was 89% in the azithromycin group and 90% in the placebo group. The median time to the first exacerbation was 266 days (95% confidence interval [CI], 227 to 313) among participants receiving azithromycin, as compared with 174 days (95% CI, 143 to 215) among participants receiving placebo (P<0.001). The frequency of exacerbations was 1.48 exacerbations per patient-year in the azithromycin group, as compared with 1.83 per patient-year in the placebo group (P=0.01), and the hazard ratio for having an acute exacerbation of COPD per patient-year in the azithromycin group was 0.73 (95% CI, 0.63 to 0.84; P<0.001). The scores on the St. Georges Respiratory Questionnaire (on a scale of 0 to 100, with lower scores indicating better functioning) improved more in the azithromycin group than in the placebo group (a mean [±SD] decrease of 2.8±12.8 vs. 0.6±11.4, P=0.004); the percentage of participants with more than the minimal clinically important difference of -4 units was 43% in the azithromycin group, as compared with 36% in the placebo group (P=0.03). Hearing decrements were more common in the azithromycin group than in the placebo group (25% vs. 20%, P=0.04). CONCLUSIONS Among selected subjects with COPD, azithromycin taken daily for 1 year, when added to usual treatment, decreased the frequency of exacerbations and improved quality of life but caused hearing decrements in a small percentage of subjects. Although this intervention could change microbial resistance patterns, the effect of this change is not known. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00325897.).

Hospital Outbreak of Middle East Respiratory Syndrome Coronavirus

BACKGROUND In September 2012, the World Health Organization reported the first cases of pneumonia caused by the novel Middle East respiratory syndrome coronavirus (MERS-CoV). We describe a cluster of health care-acquired MERS-CoV infections. METHODS Medical records were reviewed for clinical and demographic information and determination of potential contacts and exposures. Case patients and contacts were interviewed. The incubation period and serial interval (the time between the successive onset of symptoms in a chain of transmission) were estimated. Viral RNA was sequenced. RESULTS Between April 1 and May 23, 2013, a total of 23 cases of MERS-CoV infection were reported in the eastern province of Saudi Arabia. Symptoms included fever in 20 patients (87%), cough in 20 (87%), shortness of breath in 11 (48%), and gastrointestinal symptoms in 8 (35%); 20 patients (87%) presented with abnormal chest radiographs. As of June 12, a total of 15 patients (65%) had died, 6 (26%) had recovered, and 2 (9%) remained hospitalized. The median incubation period was 5.2 days (95% confidence interval [CI], 1.9 to 14.7), and the serial interval was 7.6 days (95% CI, 2.5 to 23.1). A total of 21 of the 23 cases were acquired by person-to-person transmission in hemodialysis units, intensive care units, or in-patient units in three different health care facilities. Sequencing data from four isolates revealed a single monophyletic clade. Among 217 household contacts and more than 200 health care worker contacts whom we identified, MERS-CoV infection developed in 5 family members (3 with laboratory-confirmed cases) and in 2 health care workers (both with laboratory-confirmed cases). CONCLUSIONS Person-to-person transmission of MERS-CoV can occur in health care settings and may be associated with considerable morbidity. Surveillance and infection-control measures are critical to a global public health response.

The human nasal microbiota and Staphylococcus aureus carriage.

Background Colonization of humans with Staphylococcus aureus is a critical prerequisite of subsequent clinical infection of the skin, blood, lung, heart and other deep tissues. S. aureus persistently or intermittently colonizes the nares of ∼50% of healthy adults, whereas ∼50% of the general population is rarely or never colonized by this pathogen. Because microbial consortia within the nasal cavity may be an important determinant of S. aureus colonization we determined the composition and dynamics of the nasal microbiota and correlated specific microorganisms with S. aureus colonization. Methodology/Principal Findings Nasal specimens were collected longitudinally from five healthy adults and a cross-section of hospitalized patients (26 S. aureus carriers and 16 non-carriers). Culture-independent analysis of 16S rRNA sequences revealed that the nasal microbiota of healthy subjects consists primarily of members of the phylum Actinobacteria (e.g., Propionibacterium spp. and Corynebacterium spp.), with proportionally less representation of other phyla, including Firmicutes (e.g., Staphylococcus spp.) and Proteobacteria (e.g. Enterobacter spp). In contrast, inpatient nasal microbiotas were enriched in S. aureus or Staphylococcus epidermidis and diminished in several actinobacterial groups, most notably Propionibacterium acnes. Moreover, within the inpatient population S. aureus colonization was negatively correlated with the abundances of several microbial groups, including S. epidermidis (p = 0.004). Conclusions/Significance The nares environment is colonized by a temporally stable microbiota that is distinct from other regions of the integument. Negative association between S. aureus, S. epidermidis, and other groups suggests microbial competition during colonization of the nares, a finding that could be exploited to limit S. aureus colonization.

Impact of Routine Infectious Diseases Service Consultation on the Evaluation, Management, and Outcomes of Staphylococcus aureus Bacteremia

To the Editor—Jenkins et al. [1] analyzed the role of routine infectious diseases consultation on Staphylococcus aureus bacteremia. The study did not show, however, a statistical difference in terms of treatment failure (such as bacteremia recurrence or death) between the group of patients who received routine infectious diseases consultation and the group of patients who did not receive it. With a clinically and statistically significant difference in median duration of therapy between 2 groups (29 vs. 16 days), it may be possible to argue that the infectious diseases consultation may be simply increasing the duration of therapy but not improving the outcome of patients. We do not consider that this is the case, however. The investigators reviewed cases for up to 12 weeks by protocol and actually followed-up patients for a median of ∼60 days for both groups. However, late recurrence of S. aureus infection is common, and it may have been missed in the study. A different study showed a recurrence rate of 12.3% for S. aureus bacteremia [2]. Another study reviewed 10 cases of genetically confirmed, recurrent S. aureus bacteremia, and 5 of these cases involved recurrence after an interval 160 days (range, 68 days–9 months) [3]. We think that it is too early to conclude that infectious diseases consultation does not have an impact on the clinical outcome of S. aureus bacteremia. An evaluation for a longer period of time will provide more insight into this issue.

Emergence of Fluoroquinolone Resistance in Outpatient Urinary Escherichia coli Isolates

BACKGROUND Because of high rates of trimethoprim-sulfamethoxazole resistance in Escherichia coli, Denver Health switched to levofloxacin as the initial therapy for urinary tract infections (UTIs) in 1999. We evaluated the effects of that switch 6 years later. METHODS Levofloxacin prescriptions per 1000 outpatient visits and levofloxacin resistance in outpatient E. coli were evaluated over time. E. coli isolated in 2005 were further characterized by specimen source and antimicrobial susceptibilities. Risk factors for levofloxacin-resistant E. coli UTI among nonpregnant adult outpatients were evaluated in a case-control study. RESULTS Between 1998 and 2005, levofloxacin use increased from 3.1 to 12.7 prescriptions per 1000 visits (P<.01) and resistance in outpatients increased from 1% to 9% (P<.01). Although prescriptions for sulfonamide antibiotics decreased by half during the same period, E. coli resistance to trimethoprim-sulfamethoxazole increased from 26.1% to 29.6%. Levofloxacin-resistant E. coli were more likely resistant to other antibiotics than levofloxacin-susceptible isolates (90% vs 43%, P<.0001). Risk factors for levofloxacin-resistant E. coli UTI were hospitalization (odds ratio for each week of hospitalization, 2.0; 95% confidence interval, 1.0-3.9) and use of levofloxacin (odds ratio, 5.6; 95% confidence interval, 2.1-27.5) within the previous year. CONCLUSION Fluoroquinolone prescriptions increased markedly after an institutional policy change for empiric treatment of UTI, and a rapid increase in fluoroquinolone resistance among outpatient E. coli followed. Risk factors for infection with resistant E. coli were recent hospitalization and levofloxacin use. Risk factors should be considered before initiating empiric treatment with a fluoroquinolone.

Skin and Soft-Tissue Infections Requiring Hospitalization at an Academic Medical Center: Opportunities for Antimicrobial Stewardship

BACKGROUND Although complicated skin and soft-tissue infections (SSTIs) are among the most common infections requiring hospitalization, their clinical spectrum, management, and outcomes have not been well described. METHODS We report a cohort of consecutive adult patients hospitalized for SSTI from 1 January through 31 December 2007 at an academic medical center. Cases meeting inclusion criteria were reviewed and classified as cellulitis, cutaneous abscess, or SSTI with additional complicating factors. RESULTS In total, 322 patients were included; 66 (20%) had cellulitis, 103 (32%) had cutaneous abscess, and 153 (48%) had SSTI with additional complicating factors. Injection drug use, diabetes mellitus, and alcohol abuse were common comorbidities. Serum inflammatory markers were routinely measured and blood cultures and imaging studies were routinely performed in each group. Of 150 patients with a positive culture result for an abscess, deep tissue, or blood, Staphylococcus aureus or streptococci were identified in 145 (97%). Use of antibiotics with broad aerobic gram-negative activity (61%-80% of patients) or anaerobic activity (73%-83% of patients) was frequent in each group. The median duration of therapy for cellulitis, cutaneous abscess, and SSTI with additional complicating factors was 13 (interquartile range [IQR], 10-14), 13 (IQR, 10-16), and 14 (IQR, 11-17) days, respectively. Treatment failure, recurrence, or rehospitalization due to SSTI within 30 days occurred in 12.1%, 4.9%, and 9.2% of patients, respectively. CONCLUSIONS Hospitalizations for SSTI were common; more than half were due to cellulitis or cutaneous abscess. Frequent use of potentially unnecessary diagnostic studies, broad-spectrum antibiotic therapy, and prolonged treatment courses in these patients suggest targets for antimicrobial stewardship programs.

Active screening in high-risk units is an effective and cost-avoidant method to reduce the rate of methicillin-resistant Staphylococcus aureus infection in the hospital

OBJECTIVE To evaluate the impact of active screening for methicillin-resistant Staphylococcus aureus (MRSA) on MRSA infection rates and cost avoidance in units where the risk of MRSA transmission is high. METHODS During a 15-month period, all patients admitted to our adult medical and surgical intensive care units (ICUs) were screened for MRSA nasal carriage on admission and weekly thereafter. The overall rates of all MRSA infections and of nosocomial MRSA infection in the 2 adult ICUs and the general wards were compared with rates during the 15-month period prior to the start of routine screening. The percentage of patients colonized or infected with MRSA on admission and the cost avoidance of the surveillance program were also assessed. RESULTS The overall rate of MRSA infections for all 3 areas combined decreased from 6.1 infections per 1,000 census-days in the preintervention period to 4.1 infections per 1,000 census-days in the postintervention period (P = .01). The decrease remained statistically significant when only nosocomial MRSA infections were examined (4.5 vs 2.8 infections per 1,000 census-days; P < .01), despite a corresponding increase during the postintervention period in the percentage of patients with onset of MRSA infection in the first 72 hours after admission to the general wards (46% to 81%; P < .005). A total of 3.7% of ICU patients were colonized or infected with MRSA on admission; MRSA would not have been detected in 91% of these patients if screening had not been performed. At a cost of Dollars 3,475/month for the program, we averted a mean of 2.5 MRSA infections/month for the ICUs combined, avoiding Dollars 19,714/month in excess cost in the ICUs. CONCLUSIONS Even in a setting of increasing community-associated MRSA, active MRSA screening as part of a multi-factorial intervention targeted to high-risk units may be an effective and cost-avoidant strategy for achieving a sustained decrease of MRSA infections throughout the hospital.

Prevalence of the use of central venous access devices within and outside of the intensive care unit: Results of a survey among hospitals in the prevention epicenter program of the Centers for Disease Control and Prevention

OBJECTIVE To determine the prevalence of central venous catheter (CVC) use among patients both within and outside the ICU setting. DESIGN A 1-day prevalence survey of CVC use among adult inpatients at six medical centers participating in the Prevention Epicenter Program of the CDC. Using a standardized form, observers at each Epicenter performed a hospital-wide survey, collecting data on CVC use. SETTING Inpatient wards and ICUs of six large urban teaching hospitals. RESULTS At the six medical centers, 2,459 patients were surveyed; 29% had CVCs. Among the hospitals, from 43% to 80% (mean, 59.3%) of ICU patients and from 7% to 39% (mean, 23.7%) of non-ICU patients had CVCs. Despite the lower rate of CVC use on non-ICU wards, the actual number of CVCs outside the ICUs exceeded that of the ICUs. Most catheters were inserted in the subclavian (55%) or jugular (22%) site, with femoral (6%) and peripheral (15%) sites less commonly used. The jugular (33.0% vs 16.6%; P < .001) and femoral (13.8% vs 2.7%; P < .001) sites were more frequently used in ICU patients, whereas peripherally inserted (19.9% vs 5.9%; P < .001) and subclavian (60.7% vs 47.3%; P < .001) catheters were more commonly used in non-ICU patients. CONCLUSIONS Current surveillance and infection control efforts to reduce morbidity and mortality associated with bloodstream infections concentrate on the high-risk ICU patients with CVCs. Our survey demonstrated that two-thirds of identified CVCs were not in ICU patients and suggests that more efforts should be directed to patients with CVCs who are outside the ICU.

Propionobacter acnes Infection as an Occult Cause of Postoperative Shoulder Pain: A Case Series

BackgroundInfections after shoulder surgery are potentially devastating complications. Propionibacterium acnes is recognized as a causal agent in shoulder infections. The clinical presentation is usually insidious and nonspecific, but a P. acnes infection could be an occult cause of postoperative shoulder pain.Questions/purposesWhat are the clinical and microbiologic characteristics of a postsurgical P. acnes shoulder infection and how should it be addressed?Patients and MethodsTen patients with an average age of 57 years presented with P. acnes postsurgical shoulder infection. Clinical infection signs and surgical history were assessed and joint aspirates and tissue biopsy specimens were obtained. Diagnosis was confirmed by microbiologic cultures.ResultsAt the time of confirmation of the diagnosis, clinical signs of infection were absent. C-reactive protein and erythrocyte sedimentation rates were inconsistently elevated. Cultures took a mean 7 days to confirm organism growth. The average time from surgery to diagnosis of infection was 1.8 years (range, 0.07–8.0 years). All patients underwent irrigation and débridement and were treated with antibiotics for 6 weeks.ConclusionsP. acnes shoulder infections should be considered as a cause for persistent, unexplained shoulder pain. Shoulder aspirations and tissue samples should be obtained. Surgical débridement and intravenous antibiotics are necessary treatment modalities.Level of EvidenceLevel IV, Prognostic study. See the Guidelines for Authors for a complete description of levels of evidence.

Active Surveillance Reduces the Incidence of Vancomycin-Resistant Enterococcal Bacteremia

The impact of active surveillance of patients at risk for infection with vancomycin-resistant enterococci (VRE) was examined, and VRE bacteremia rates and the degree of VRE clonality in 2 similar neighboring hospitals were compared. Hospital A did not routinely screen patients for VRE rectal colonization; hospital B actively screened high-risk patients. Retrospective observations were made over the course of 6 years, beginning when initial VRE bloodstream isolates were recovered at each institution. The rate of VRE bacteremia was 2.1-fold higher at hospital A, and the majority of hospital A isolates were clonally related: 4 clones were responsible for infection in >75% of patients with VRE bacteremia, and isolates from 30% of patients were from the most common clone. The 4 most common clones at hospital B were responsible for infection in 37% of patients, and isolates from 14.5% of patients were from the most common clone. Lower VRE bacteremia rates and a more polyclonal population, representing less horizontal transmission, may result from routine screening of patients who are at risk for VRE and prompt contact isolation of colonized individuals.