Omadacycline for Acute Bacterial Skin and Skin Structure Infections.

BACKGROUND: Within the last decade, methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a frequent cause of purulent skin and soft tissue infections. New therapeutic options are being investigated for these infections. METHODS: We report an integrated analysis of 2 randomized, controlled studies involving omadacycline, a novel aminomethylcycline, and linezolid for the treatment of acute bacterial skin and skin structure infections (ABSSSI). Omadacycline in Acute Skin and Skin Structure Infections Study 1 (OASIS-1) initiated patients on intravenous omadacycline or linezolid, with the option to transition to an oral formulation after day 3. OASIS-2 was an oral-only study of omadacycline versus linezolid. RESULTS: In total, 691 patients received omadacycline and 689 patients received linezolid. Infection types included wound infection in 46.8% of patients, cellulitis/erysipelas in 30.5%, and major abscess in 22.7%. Pathogens were identified in 73.2% of patients. S. aureus was detected in 74.7% and MRSA in 32.4% of patients in whom a pathogen was identified. Omadacycline was noninferior to linezolid using the Food and Drug Administration primary endpoint of early clinical response (86.2% vs 83.9%; difference 2.3, 95% confidence interval -1.5 to 6.2) and using the European Medicines Agency primary endpoint of investigator-assessed clinical response at the posttreatment evaluation. Clinical responses were similar across different infection types and infections caused by different pathogens. Treatment-emergent adverse events, mostly described as mild or moderate, were reported by 51.1% of patients receiving omadacycline and 41.2% of those receiving linezolid. CONCLUSIONS: Omadacycline was effective and safe in ABSSSI. CLINICAL TRIALS REGISTRATION: NCT02378480 and NCT02877927.

Effect of Initial Bedside Ultrasonography on Emergency Department Skin and Soft Tissue Infection Management.

STUDY OBJECTIVE: We examine the utility of emergency department (ED) ultrasonography in treatment of skin and soft tissue infections. METHODS: We enrolled ED patients with skin and soft tissue infections and surveyed clinicians in regard to their pre-ultrasonography certainty about the presence or absence of an abscess, their planned management, post-ultrasonography findings, and actual management. We determined sensitivity and specificity of ultrasonography and clinical evaluation, and assessed appropriateness of management changes based on initial clinical assessment and outcomes through 1-week follow-up. RESULTS: Among 1,216 patients, clinicians were uncertain of abscess presence in 105 cases (8.6%) and certain for 1,111 cases (91.4%). Based on surgical exploration and follow-up through 1 week, sensitivity and specificity for abscess detection by clinical evaluation were 90.3% and 97.7%, and by ultrasonography were 94.0% and 94.1%, respectively. Among 1,111 cases for which the clinician was certain, sensitivity and specificity of clinical evaluation were 96.6% and 97.3% compared with ultrasonographic evaluation sensitivity and specificity of 95.7% and 96.2%, respectively. Of 105 uncertain cases, sensitivity and specificity of ultrasonography were 68.5% and 80.4%. Ultrasonography changed management in 13 of 1,111 certain cases (1.2%), appropriately in 10 of 13 (76.9%) and inappropriately in 3 of 13 (23.1%). Of 105 uncertain cases, ultrasonography changed management in 25 (23.8%), appropriately in 21 of 25 (84.0%) and inappropriately in 4 of 25 (16.0%). CONCLUSION: Ultrasonography rarely changed management when clinicians were certain about the presence or absence of an abscess. When they were uncertain, ultrasonography changed drainage decisions in approximately one quarter of cases, of which most (84%) were appropriate.

Subgroup Analysis of Antibiotic Treatment for Skin Abscesses.

STUDY OBJECTIVE: Two large randomized trials recently demonstrated efficacy of methicillin-resistant Staphylococcus aureus (MRSA)-active antibiotics for drained skin abscesses. We determine whether outcome advantages observed in one trial exist across lesion sizes and among subgroups with and without guideline-recommended antibiotic indications. METHODS: We conducted a planned subgroup analysis of a double-blind, randomized trial at 5 US emergency departments, demonstrating superiority of trimethoprim-sulfamethoxazole (320/1,600 mg twice daily for 7 days) compared with placebo for patients older than 12 years with a drained skin abscess. We determined between-group differences in rates of clinical (no new antibiotics) and composite cure (no new antibiotics or drainage) through 7 to 14 and 42 to 56 days after treatment among subgroups with and without abscess cavity or erythema diameter greater than or equal to 5 cm, history of MRSA, fever, diabetes, and comorbidities. We also evaluated treatment effect by lesion size and culture result. RESULTS: Among 1,057 mostly adult participants, median abscess cavity and erythema diameters were 2.5 cm (range 0.1 to 16.0 cm) and 6.5 cm (range 1.0 to 38.5), respectively; 44.3% grew MRSA. Overall, for trimethoprim-sulfamethoxazole and placebo groups, clinical cure rate at 7 to 14 days was 92.9% and 85.7%; composite cure rate at 7 to 14 days was 86.5% and 74.3%, and at 42 to 56 days, it was 82.4% and 70.2%. For all outcomes, across lesion sizes and among subgroups with and without guideline antibiotic criteria, trimethoprim-sulfamethoxazole was associated with improved outcomes. Treatment effect was greatest with history of MRSA infection, fever, and positive MRSA culture. CONCLUSION: Treatment with trimethoprim-sulfamethoxazole was associated with improved outcomes regardless of lesion size or guideline antibiotic criteria.

Effect of Cephalexin Plus Trimethoprim-Sulfamethoxazole vs Cephalexin Alone on Clinical Cure of Uncomplicated Cellulitis: A Randomized Clinical Trial.

IMPORTANCE: Emergency department visits for skin infections in the United States have increased with the emergence of methicillin-resistant Staphylococcus aureus (MRSA). For cellulitis without purulent drainage, ß-hemolytic streptococci are presumed to be the predominant pathogens. It is unknown if antimicrobial regimens possessing in vitro MRSA activity provide improved outcomes compared with treatments lacking MRSA activity. OBJECTIVE: To determine whether cephalexin plus trimethoprim-sulfamethoxazole yields a higher clinical cure rate of uncomplicated cellulitis than cephalexin alone. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, double-blind, randomized superiority trial in 5 US emergency departments among outpatients older than 12 years with cellulitis and no wound, purulent drainage, or abscess enrolled from April 2009 through June 2012. All participants had soft tissue ultrasound performed at the time of enrollment to exclude abscess. Final follow-up was August 2012. INTERVENTIONS: Cephalexin, 500 mg 4 times daily, plus trimethoprim-sulfamethoxazole, 320 mg/1600 mg twice daily, for 7 days (n = 248 participants) or cephalexin plus placebo for 7 days (n = 248 participants). MAIN OUTCOMES AND MEASURES: The primary outcome determined a priori in the per-protocol group was clinical cure, defined as absence of these clinical failure criteria at follow-up visits: fever; increase in erythema (>25%), swelling, or tenderness (days 3-4); no decrease in erythema, swelling, or tenderness (days 8-10); and more than minimal erythema, swelling, or tenderness (days 14-21). A clinically significant difference was defined as greater than 10%. RESULTS: Among 500 randomized participants, 496 (99%) were included in the modified intention-to-treat analysis and 411 (82.2%) in the per-protocol analysis (median age, 40 years [range, 15-78 years]; 58.4% male; 10.9% had diabetes). Median length and width of erythema were 13.0 cm and 10.0 cm. In the per-protocol population, clinical cure occurred in 182 (83.5%) of 218 participants in the cephalexin plus trimethoprim-sulfamethoxazole group vs 165 (85.5%) of 193 in the cephalexin group (difference, -2.0%; 95% CI, -9.7% to 5.7%; P = .50). In the modified intention-to-treat population, clinical cure occurred in 189 (76.2%) of 248 participants in the cephalexin plus trimethoprim-sulfamethoxazole group vs 171 (69.0%) of 248 in the cephalexin group (difference, 7.3%; 95% CI, -1.0% to 15.5%; P = .07). Between-group adverse event rates and secondary outcomes through 7 to 9 weeks, including overnight hospitalization, recurrent skin infections, and similar infection in household contacts, did not differ significantly. CONCLUSIONS AND RELEVANCE: Among patients with uncomplicated cellulitis, the use of cephalexin plus trimethoprim-sulfamethoxazole compared to cephalexin alone did not result in higher rates of clinical resolution of cellulitis in the per-protocol analysis. However, because imprecision around the findings in the modified intention-to-treat analysis included a clinically important difference favoring cephalexin plus trimethoprim-sulfamethoxazole, further research may be needed. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00729937.

Clostridium difficile Infection Among US Emergency Department Patients With Diarrhea and No Vomiting.

STUDY OBJECTIVE: The incidence of Clostridium difficile infection has increased and has been observed among persons from the community who have not been exposed to antibiotics or health care settings. Our aims are to determine prevalence of C difficile infection among emergency department (ED) patients with diarrhea and the prevalence among patients without traditional risk factors. METHODS: We conducted a prospective observational study of patients aged 2 years or older with diarrhea (≥3 episodes/24 hours) and no vomiting in 10 US EDs (2010 to 2013). We confirmed C difficile infection by positive stool culture result and toxin assay. C difficile infection risk factors were antibiotic use or overnight health care stay in the previous 3 months or previous C difficile infection. We typed strains with pulsed-field gel electrophoresis. RESULTS: Of 422 participants, median age was 46 years (range 2 to 94 years), with median illness duration of 3.0 days and 43.4% having greater than or equal to 10 episodes of diarrhea during the previous 24 hours. At least one risk factor for C difficile infection was present in 40.8% of participants; 25.9% were receiving antibiotics, 26.9% had health care stay within the previous 3 months, and 3.3% had previous C difficile infection. Forty-three participants (10.2%) had C difficile infection; among these, 24 (55.8%) received antibiotics and 19 (44.2%) had health care exposure; 17 of 43 (39.5%) lacked any risk factor. Among participants without risk factors, C difficile infection prevalence was 6.9%. The most commonly identified North American pulsed-field gel electrophoresis (NAP) strains were NAP type 1 (23.3%) and NAP type 4 (16.3%). CONCLUSION: Among mostly adults presenting to US EDs with diarrhea and no vomiting, C difficile infection accounted for approximately 10%. More than one third of patients with C difficile infection lacked traditional risk factors for the disease. Among participants without traditional risk factors, prevalence of C difficile infection was approximately 7%.

Fluoroquinolone-Resistant and Extended-Spectrum ß-Lactamase-Producing Escherichia coli Infections in Patients with Pyelonephritis, United States(1).

For 2013-2014, we prospectively identified US adults with flank pain, temperature >38.0°C, and a diagnosis of acute pyelonephritis, confirmed by culture. Cultures from 453 (86.9%) of 521 patients grew Escherichia coli. Among E. coli isolates from 272 patients with uncomplicated pyelonephritis and 181 with complicated pyelonephritis, prevalence of fluoroquinolone resistance across study sites was 6.3% (range by site 0.0%-23.1%) and 19.9% (0.0%-50.0%), respectively; prevalence of extended-spectrum ß-lactamase (ESBL) production was 2.6% (0.0%-8.3%) and 12.2% (0.0%-17.2%), respectively. Ten (34.5%) of 29 patients with ESBL infection reported no exposure to antimicrobial drugs, healthcare, or travel. Of the 29 patients with ESBL infection and 53 with fluoroquinolone-resistant infection, 22 (75.9%) and 24 (45.3%), respectively, were initially treated with in vitro inactive antimicrobial drugs. Prevalence of fluoroquinolone resistance exceeds treatment guideline thresholds for alternative antimicrobial drug strategies, and community-acquired ESBL-producing E. coli infection has emerged in some US communities.

A Randomized Trial of Clindamycin Versus Trimethoprim-sulfamethoxazole for Uncomplicated Wound Infection.

BACKGROUND: With the emergence of community-associated methicillin-resistant Staphylococcus aureus (MRSA) in the United States, visits for skin infections greatly increased. Staphylococci and streptococci are considered predominant causes of wound infections. Clindamycin and trimethoprim-sulfamethoxazole (TMP-SMX) are commonly prescribed, but the efficacy of TMP-SMX has been questioned. METHODS: We conducted a randomized, double-blind, superiority trial at 5 US emergency departments. Patients >12 years of age with an uncomplicated wound infection received oral clindamycin 300 mg 4 times daily or TMP-SMX 320 mg/1600 mg twice daily, each for 7 days. We compared the primary outcome, wound infection cure at 7-14 days, and secondary outcomes through 6-8 weeks after treatment, in the per-protocol population. RESULTS: Subjects had a median age of 40 years (range, 14-76 years); 40.1% of wound specimens grew MRSA, 25.7% methicillin-susceptible S. aureus, and 5.0% streptococci. The wound infection was cured at 7-14 days in 187 of 203 (92.1%) clindamycin-treated and 182 of 198 (91.9%) TMP-SMX-treated subjects (difference, 0.2%; 95% confidence interval [CI], -5.8% to 6.2%; P = not significant). The clindamycin group had a significantly lower rate of recurrence at 7-14 days (1.5% vs 6.6%; difference, -5.1%; 95% CI, -9.4% to -.8%) and through 6-8 weeks following treatment (2.0% vs 7.1%; difference, -5.1%; 95% CI, -9.7% to -.6%). Other secondary outcomes were statistically similar between groups but tended to favor clindamycin. Adverse event rates were similar. CONCLUSIONS: In settings where MRSA is prevalent, clindamycin and TMP-SMX produce similar cure and adverse event rates among patients with an uncomplicated wound infection. Further study evaluating differential effects of antibiotics on recurrent infection may be warranted. CLINICAL TRIALS REGISTRATION: NCT00729937.

Trimethoprim-Sulfamethoxazole versus Placebo for Uncomplicated Skin Abscess.

BACKGROUND: U.S. emergency department visits for cutaneous abscess have increased with the emergence of methicillin-resistant Staphylococcus aureus (MRSA). The role of antibiotics for patients with a drained abscess is unclear. METHODS: We conducted a randomized trial at five U.S. emergency departments to determine whether trimethoprim-sulfamethoxazole (at doses of 320 mg and 1600 mg, respectively, twice daily, for 7 days) would be superior to placebo in outpatients older than 12 years of age who had an uncomplicated abscess that was being treated with drainage. The primary outcome was clinical cure of the abscess, assessed 7 to 14 days after the end of the treatment period. RESULTS: The median age of the participants was 35 years (range, 14 to 73); 45.3% of the participants had wound cultures that were positive for MRSA. In the modified intention-to-treat population, clinical cure of the abscess occurred in 507 of 630 participants (80.5%) in the trimethoprim-sulfamethoxazole group versus 454 of 617 participants (73.6%) in the placebo group (difference, 6.9 percentage points; 95% confidence interval [CI], 2.1 to 11.7; P=0.005). In the per-protocol population, clinical cure occurred in 487 of 524 participants (92.9%) in the trimethoprim-sulfamethoxazole group versus 457 of 533 participants (85.7%) in the placebo group (difference, 7.2 percentage points; 95% CI, 3.2 to 11.2; P<0.001). Trimethoprim-sulfamethoxazole was superior to placebo with respect to most secondary outcomes in the per-protocol population, resulting in lower rates of subsequent surgical drainage procedures (3.4% vs. 8.6%; difference, -5.2 percentage points; 95% CI, -8.2 to -2.2), skin infections at new sites (3.1% vs. 10.3%; difference, -7.2 percentage points; 95% CI, -10.4 to -4.1), and infections in household members (1.7% vs. 4.1%; difference, -2.4 percentage points; 95% CI, -4.6 to -0.2) 7 to 14 days after the treatment period. Trimethoprim-sulfamethoxazole was associated with slightly more gastrointestinal side effects (mostly mild) than placebo. At 7 to 14 days after the treatment period, invasive infections had developed in 2 of 524 participants (0.4%) in the trimethoprim-sulfamethoxazole group and in 2 of 533 participants (0.4%) in the placebo group; at 42 to 56 days after the treatment period, an invasive infection had developed in 1 participant (0.2%) in the trimethoprim-sulfamethoxazole group. CONCLUSIONS: In settings in which MRSA was prevalent, trimethoprim-sulfamethoxazole treatment resulted in a higher cure rate among patients with a drained cutaneous abscess than placebo. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT00729937.).

Diseases Transmitted by Cats.

Humans and cats have shared a close relationship since ancient times. Millions of cats are kept as household pets, and 34% of households have cats. There are numerous diseases that may be transmitted from cats to humans. General modes of transmission, with some overlapping features, can occur through inhalation (e.g., bordetellosis); vector-borne spread (e.g., ehrlichiosis); fecal-oral route (e.g., campylobacteriosis); bite, scratch, or puncture (e.g., rabies); soil-borne spread (e.g., histoplasmosis); and direct contact (e.g., scabies). It is also likely that the domestic cat can potentially act as a reservoir for many other zoonoses that are not yet recognized. The microbiology of cat bite wound infections in humans is often polymicrobial with a broad mixture of aerobic (e.g., Pasteurella, Streptococcus, Staphylococcus) and anaerobic (e.g., Fusobacterium, Porphyromonas, Bacteroides) microorganisms. Bacteria recovered from infected cat bite wounds are most often reflective of the oral flora of the cat, which can also be influenced by the microbiome of their ingested prey and other foods. Bacteria may also originate from the victim's own skin or the physical environment at the time of injury.

Association of pyuria and clinical characteristics with the presence of urinary tract infection among patients with acute nephrolithiasis.

STUDY OBJECTIVE: Pyuria is a useful indicator of urinary tract infection among patients with compatible symptoms; however, its utility has not been adequately investigated among patients with acute nephrolithiasis. Therefore, we examine performance characteristics of pyuria and other clinical and laboratory correlates for urinary tract infection among patients with acute nephrolithiasis. METHODS: A single-center prospective observational study examining the performance characteristics of pyuria and other clinical correlates for urinary tract infection was conducted among patients older than 17 years and presenting with acute nephrolithiasis confirmed by computed tomography and for whom urine culture was obtained. RESULTS: Of 360 patients with acute nephrolithiasis, 28 (7.8%) had urinary tract infection, defined as growth of a single uropathogen at greater than or equal to 10(3) colony-forming units/mL. For the presence of urinary tract infection, pyuria level greater than 5 WBCs/high-power field (hpf) had a sensitivity of 86% and specificity of 79%; greater than 20 WBCs/hpf had a sensitivity of 68% and specificity of 93%. In 307 patients who lacked history of fever or measured temperature greater than 37.9°C (100.2°F), pyuria level greater than 5 WBCs/hpf had a sensitivity of 79% and specificity of 81% for urinary tract infection; greater than 20 WBCs/hpf had a sensitivity of 57% and specificity of 94%. Patients with urinary tract infection more often were female; had a history of dysuria, frequent urination, chills, urinary tract infection, or subjective fever; or had measured temperature of greater than 37.9°C (100.2°F). CONCLUSION: About 8% of patients presenting with acute nephrolithiasis have urinary tract infection, in many without clinical findings of infection, and pyuria has only a moderate accuracy in identifying urinary tract infection in this setting. Clinical features of urinary tract infection, a greater degree of pyuria, and female sex increases the likelihood of infection.

Acute bacterial skin infections: developments since the 2005 Infectious Diseases Society of America (IDSA) guidelines.

BACKGROUND: Patients with acute bacterial skin and skin structure infections (ABSSSI) commonly present to Emergency Departments (EDs) where physicians encounter a wide spectrum of disease severity. The prevalence of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) has increased in the past decade, and CA-MRSA is now a predominant cause of purulent ABSSSI in the United States (US). OBJECTIVES: This article reviews significant developments since the most recent Infectious Diseases Society of America (IDSA) guidelines for the management of ABSSSI in the CA-MRSA era, focusing on recent studies and recommendations for managing CA-MRSA, newer antimicrobials with improved MRSA activity, new diagnostic technologies, and options for outpatient parenteral antimicrobial therapy (OPAT). DISCUSSION: The increasing prevalence of CA-MRSA has led the IDSA and other organizations to recommend empiric coverage of CA-MRSA for purulent ABSSSI. The availability of rapid MRSA detection assays from skin and soft tissue swabs could potentially facilitate earlier selection of targeted antimicrobial therapy. Several newer intravenous antibiotics with expanded MRSA coverage, including ceftaroline fosamil, daptomycin, linezolid, and telavancin, may be utilized for treatment of ABSSSI. OPAT may be an option for intravenous administration of antibiotics in selected patients and may prevent or shorten hospitalizations, decrease readmission rates, and reduce nosocomial infections and complications. CONCLUSION: The growing prevalence of CA-MRSA associated with ABSSSI in the US has a significant impact on clinical management decisions in the ED. Recent availability of new diagnostic testing and therapeutic options may help meet the demand for effective antistaphylococcal agents.

Association Between Appendectomy and Clostridium difficile Infection.

BACKGROUND: Recent theory proposes that the appendix functions as a reservoir for commensal bacteria, and serves to re-inoculate the colon with normal flora in the event of pathogen exposure or purging of intestinal flora. If true, we reasoned that flora from a normal appendix could provide protection against Clostridium difficile. We conducted this investigation to examine the protective effect of an intact appendix and test the hypothesis that prior appendectomy will be more common among patients with a positive test for C. difficile as compared with patients who test negative. METHODS: We contacted patients who had undergone C. difficile testing and asked them whether or not they had a prior appendectomy. Using their responses and results from Toxin A & B EIA tests, we calculated the difference in appendectomy rates between those who tested positive for C. difficile, and those who tested negative. We considered a positive 15% absolute difference to represent a significant increase in appendectomy rate. RESULTS: We enrolled 257 patients. Among the 136 who tested positive for C. difficile, 27 (19.9%) had prior appendectomies, while among 121 patients testing negative for C. difficile, 38 (31.4%) had prior appendectomies, yielding a difference in appendectomy rates of -11.6% (95% Confidence Interval: -21.6% to -0.9%). CONCLUSIONS: The rate of prior appendectomy was actually lower among patients with a positive C. difficile test as compared to those with a negative test. Conversely, patients who tested positive for C. difficile were more likely to have an intact appendix than those who tested negative. These results suggest that rather than being protective, an intact appendix appears to promote C. difficile acquisition, carriage, and disease. KEYWORDS: Clostridium difficile; Appendix; Appendectomy; Microbial reservoir; Infection.

Microbiology of animal bite wound infections.

The microbiology of animal bite wound infections in humans is often polymicrobial, with a broad mixture of aerobic and anaerobic microorganisms. Bacteria recovered from infected bite wounds are most often reflective of the oral flora of the biting animal, which can also be influenced by the microbiome of their ingested prey and other foods. Bacteria may also originate from the victim's own skin or the physical environment at the time of injury. Our review has focused on bite wound infections in humans from dogs, cats, and a variety of other animals such as monkeys, bears, pigs, ferrets, horses, sheep, Tasmanian devils, snakes, Komodo dragons, monitor lizards, iguanas, alligators/crocodiles, rats, guinea pigs, hamsters, prairie dogs, swans, and sharks. The medical literature in this area has been made up mostly of small case series or case reports. Very few studies have been systematic and are often limited to dog or cat bite injuries. Limitations of studies include a lack of established or inconsistent criteria for an infected wound and a failure to utilize optimal techniques in pathogen isolation, especially for anaerobic organisms. There is also a lack of an understanding of the pathogenic significance of all cultured organisms. Gathering information and conducting research in a more systematic and methodical fashion through an organized research network, including zoos, veterinary practices, and rural clinics and hospitals, are needed to better define the microbiology of animal bite wound infections in humans.

Decision instrument for the isolation of pneumonia patients with suspected pulmonary tuberculosis admitted through US emergency departments.

STUDY OBJECTIVE: Many patients with pneumonia are admitted to respiratory isolation for possible tuberculosis (TB), but most do not have active TB. We created a decision instrument to predict which pneumonia patients do not need admission to a TB isolation bed. METHODS: The design was a prospective case series conducted in 11 university-affiliated, urban, US emergency departments (EDs) (EMERGEncy ID NET). Participants were patients admitted to the hospital through the ED with a diagnosis of pneumonia or suspected TB. The main outcome measure was derivation and validation of a sensitive decision instrument to identify patients not having TB (and not requiring isolation) according to clinical data and chest radiographs. RESULTS: Of 5,079 pneumonia patients, 224 (4.4%) had pulmonary TB according to sputum cultures or tissue staining. The instrument derived to predict which patients did not have pulmonary TB included no TB history or previous positive tuberculin skin test result, nonimmigrant, not homeless, not recently incarcerated, no recent weight loss, and no apical infiltrate or cavitary lesion on plain chest radiograph. When tested on the validation subgroup, the decision instrument exhibited a negative predictive value of 99.7% (95% confidence interval [CI] 99.1% to 99.9%), and a sensitivity of 96.4% (95% CI 91.1% to 99.0%). CONCLUSION: A decision instrument can accurately predict which patients with pneumonia do not require admission to TB isolation rooms.

Prevalence and risk factor analysis of trimethoprim-sulfamethoxazole- and fluoroquinolone-resistant Escherichia coli infection among emergency department patients with pyelonephritis.

BACKGROUND: High rates of resistance to trimethoprim-sulfamethoxazole (TMP-SMX) among uropathogenic Escherichia coli are recognized, and concerns exist about emerging fluoroquinolone resistance. METHODS: Adults presenting to 11 US emergency departments with (1) flank pain and/or costovertebral tenderness, (2) temperature >38 degrees C, and (3) a presumptive diagnosis of pyelonephritis were enrolled; patients for whom 1 uropathogen grew on culture were analyzed. Epidemiologic and clinical data were collected at the time of care. The prevalence of E. coli in vitro antibiotic resistance and risk factors associated with TMP-SMX-resistant E. coli infection were determined. RESULTS: Among 403 women with uncomplicated pyelonephritis caused by E. coli, the mean site rate of E. coli resistance to TMP-SMX was 24% (range, 13%-45%). Mean site rates of E. coli resistance to ciprofloxacin and levofloxacin were 1% and 3%, respectively. Only TMP-SMX exposure within 2 days before presentation and Hispanic ethnicity were associated with E. coli resistance to TMP-SMX (compared with resistance rates of approximately 20% among women lacking these risk factors); antibiotic exposure within 3-60 days before presentation, health care setting exposure within 30 days before presentation, history of urinary tract infections, and age >55 years were not associated with E. coli resistance to TMP-SMX. Among 207 patients with complicated pyelonephritis, mean site rates of E. coli resistance to ciprofloxacin and levofloxacin were 5% and 6%, respectively. CONCLUSIONS: These results suggest that the prevalence of TMP-SMX-resistant infection among patients with uncomplicated pyelonephritis is > or =20% in many areas of the United States, and risk stratification cannot identify patients at low risk of infection. Rates of fluoroquinolone-resistant E. coli infection appear to be low among patients with uncomplicated pyelonephritis but higher among those with complicated infections. Fluoroquinolones should remain to be the preferred empirical treatment for women with uncomplicated pyelonephritis.

Health care-associated pneumonia: identification and initial management in the ED.

Traditionally, pneumonia is categorized by epidemiologic factors into community-acquired pneumonia (CAP), hospital-acquired pneumonia (HAP), and ventilator-associated pneumonia (VAP). Microbiologic studies have shown that the organisms which cause infections in HAP and VAP differ from CAP in epidemiology and resistance patterns. Patients with HAP or VAP are at higher risk for harboring resistant organisms. Other historical features that potentially place patients at a higher risk for being infected with resistant pathogens and organisms not commonly associated with CAP include history of recent admission to a health care facility, residence in a long-term care or nursing home facility, attendance at a dialysis clinic, history of recent intravenous antibiotic therapy, chemotherapy, and wound care. Because these "risk factors" have health care exposure as a common feature, patients presenting with pneumonia having these historical features have been more recently categorized as having health care-associated pneumonia (HCAP). This publication was prepared by the HCAP Working Group, which is comprised of nationally recognized experts in emergency medicine, infectious diseases, and pulmonary and critical care medicine. The aim of this article is to create awareness of the entity known as HCAP and to provide knowledge of its identification and initial management in the emergency department.

Severe sepsis and septic shock in the emergency department.

Increased attention has focused recently on the acute management of severe sepsis and septic shock, conditions that represent the end-stage systemic deterioration of overwhelming infection. Clinical trials have identified new therapies and management approaches that, when applied early, appear to reduce mortality. Practice guidelines have been advanced by critical care societies, and many of the proposed interventions involve therapies other than antimicrobials directed at hemodynamic resuscitation or addressing adverse effects of the inflammatory cascade. Although many emergency departments (EDs) are now adopting treatment protocols for sepsis that are based on published treatment guidelines, recent research calls many of the initial recommendations into question, and validation trials of some of these approaches are ongoing. This article reviews the initial evaluation and treatment considerations of sepsis in the ED setting.

Emergency department management of meningitis and encephalitis.

Bacterial meningitis and viral encephalitis are infectious disease emergencies that can cause significant patient morbidity and mortality. Clinicians use epidemiologic, historical, and physical examination findings to identify patients at risk for these infections, and central nervous system (CNS) imaging and lumbar puncture (LP) may be needed to further evaluate for these diagnoses. The diagnosis of bacterial meningitis can be challenging, as patients often lack some of the characteristic findings of this disease with presentations that overlap with more common disorders seen in the emergency department. This article addresses considerations in clinical evaluation, need for CNS imaging before LP, interpretation of cerebrospinal fluid results, standards for and effects of timely antibiotic administration, and recommendations for specific antimicrobial therapy and corticosteroids.