Emergence of Extended-Spectrum ß-Lactamase Urinary Tract Infections Among Hospitalized Emergency Department Patients in the United States.

STUDY OBJECTIVE: Enterobacteriaceae resistant to ceftriaxone, mediated through extended-spectrum ß-lactamases (ESBLs), commonly cause urinary tract infections worldwide, but have been less prevalent in North America. Current US rates are unknown. We determine Enterobacteriaceae antimicrobial resistance rates among US emergency department (ED) patients hospitalized for urinary tract infection. METHODS: We prospectively enrolled adults hospitalized for urinary tract infection from 11 geographically diverse university-affiliated hospital EDs during 2018 to 2019. Among participants with culture-confirmed infection, we evaluated prevalence of antimicrobial resistance, including that caused by ESBL-producing Enterobacteriaceae, resistance risk factors, and time to in vitro-active antibiotics. RESULTS: Of 527 total participants, 444 (84%) had cultures that grew Enterobacteriaceae; 89 of 435 participants (20.5%; 95% confidence interval 16.9% to 24.5%; 4.6% to 45.4% by site) whose isolates had confirmatory testing had bacteria that were ESBL producing. The overall prevalence of ESBL-producing Enterobacteriaceae infection among all participants with urinary tract infection was 17.2% (95% confidence interval 14.0% to 20.7%). ESBL-producing Enterobacteriaceae infection risk factors were hospital, long-term care, antibiotic exposure within 90 days, and a fluoroquinolone- or ceftriaxone-resistant isolate within 1 year. Enterobacteriaceae resistance rates for other antimicrobials were fluoroquinolone 32.3%, gentamicin 13.7%, amikacin 1.3%, and meropenem 0.3%. Ceftriaxone was the most common empirical antibiotic. In vitro-active antibiotics were not administered within 12 hours of presentation to 48 participants (53.9%) with ESBL-producing Enterobacteriaceae infection, including 17 (58.6%) with sepsis. Compared with other Enterobacteriaceae infections, ESBL infections were associated with longer time to in vitro-active treatment (17.3 versus 3.5 hours). CONCLUSION: Among adults hospitalized for urinary tract infection in many US locations, ESBL-producing Enterobacteriaceae have emerged as a common cause of infection that is often not initially treated with an in vitro-active antibiotic.

Intravenous Acetaminophen Overdose in an Infant With Toxicokinetic Data.

CASE REPORT: A 12-month-old (former 24 week gestational age), 8.7 kg male was hospitalized after an uneventful colostomy reversal. In the postoperative unit, the patient unintentionally received 1000 mg IV (114.9 mg/kg) acetaminophen instead of the intended 100 mg IV. Serial acetaminophen concentrations were drawn. The patient received IV Nacetylcysteine and ultimately had no adverse outcomes. DISCUSSION: This case report adds to the existing literature regarding toxicokinetics of IV APAP in infants. Our patient had a calculated ke of 0.263 h-1, correlating with a half-life of 2.63 hours. Based on current available data, the half-life of IV APAP in infants varies (2.6 to 4.9 hours). The reason for this variation is unknown and further research is needed in this area.

Hierarchy of human IgG recognition within the Staphylococcus aureus immunome.

Staphylococcus aureus is an opportunistic pathogen that causes a range of serious infections associated with significant morbidity, by strains increasingly resistant to antibiotics. However, to date all candidate vaccines have failed to induce protective immune responses in humans. We need a more comprehensive understanding of the antigenic targets important in the context of human infection. To investigate infection-associated immune responses, patients were sampled at initial presentation and during convalescence from three types of clinical infection; skin and soft tissue infection (SSTI), prosthetic joint infection (PJI) and pediatric hematogenous osteomyelitis (PHO). Reactivity of serum IgG was tested with an array of recombinant proteins, representing over 2,652 in-vitro-translated open reading frames (ORFs) from a community-acquired methicillin-resistant S. aureus USA300 strain. High-level reactivity was demonstrated for 104 proteins with serum IgG in all patient samples. Overall, high-level IgG-reactivity was most commonly directed against a subset of secreted proteins. Although based on limited surveys, we found subsets of S. aureus proteins with differential reactivity with serum samples from patients with different clinical syndromes. Together, our studies have revealed a hierarchy within the diverse proteins of the S. aureus "immunome", which will help to advance efforts to develop protective immunotherapeutic agents.

Human Memory B Cells Targeting Staphylococcus aureus Exotoxins Are Prevalent with Skin and Soft Tissue Infection.

Staphylococcus aureus is a Gram-positive opportunistic pathogen that causes superficial and invasive infections in the hospital and community. High mortality from infection emphasizes the need for improved methods for prevention and treatment. Although S. aureus possesses an arsenal of virulence factors that contribute to evasion of host defenses, few studies have examined long-term humoral and B-cell responses. Adults with acute-phase skin and soft tissue infections were recruited; blood samples were obtained; and S. aureus isolates, including methicillin-resistant strains, were subjected to genomic sequence analysis. In comparisons of acute-phase sera with convalescent-phase sera, a minority (37.5%) of patients displayed 2-fold or greater increases in antibody titers against three or more S. aureus antigens, whereas nearly half exhibited no changes, despite the presence of toxin genes in most infecting strains. Moreover, enhanced antibody responses waned over time, which could reflect a defect in B-cell memory or long-lived plasma cells. However, memory B cells reactive with a range of S. aureus antigens were prevalent at both acute-phase and convalescent-phase time points. While some memory B cells exhibited toxin-specific binding, those cross-reactive with structurally related leucocidin subunits were dominant across patients, suggesting the targeting of conserved epitopes. Memory B-cell reactivity correlated with serum antibody levels for selected S. aureus exotoxins, suggesting a relationship between the cellular and humoral compartments. Overall, although there was no global defect in the representation of anti-S. aureus memory B cells, there was evidence of restrictions in the range of epitopes recognized, which may suggest potential therapeutic approaches for augmenting host defenses.IMPORTANCE The contribution of B-cell memory and long-term antibody responses to host defenses against S. aureus exotoxins remains poorly understood. Our studies confirmed that infection did not commonly lead to enhanced long-term humoral responses. Whereas circulating memory B cells against S. aureus secreted exotoxins were prevalent, they were dominated by cross-reactivity with structurally related leucocidin subunits, consistent with recognition of conserved epitopes. These findings also provide the first evidence of a relationship between the reactivity of antistaphylococcal circulating memory B cells and serum antibody levels. In general, infection was not associated with a global defect in B-cell memory for S. aureus secreted factors, and responses were highly dominated by cross-reactivity to structurally related exotoxins, which arguably may alone be suboptimal in providing host defenses. Our studies illuminate aspects of the S. aureus-host relationship that may better inform strategies for the development of an effective protective vaccine.

Evaluation and treatment of patients with severely elevated blood pressure in academic emergency departments: a multicenter study.

STUDY OBJECTIVE: Current guidelines advise that emergency department (ED) patients with severely elevated blood pressure be evaluated for acute target organ damage, have their medical regimen adjusted, and be instructed to follow up promptly for reassessment. We examine factors associated with performance of recommended treatment of patients with severely elevated blood pressure. METHODS: Observational study performed during 1 week at 4 urban, academic EDs. Severely elevated blood pressure was defined as systolic blood pressure greater than or equal to 180 mm Hg or diastolic blood pressure greater than or equal to 110 mm Hg on at least 1 measurement. ED staff were blinded to the study purpose. Demographics, presenting complaints, vital signs, tests ordered, medications administered, disposition, and discharge instructions were recorded, and associations were tested in bivariate analyses. RESULTS: Severely elevated blood pressure was noted in 423 patients. Serum chemistry was obtained in 73% of patients, ECG in 53% of patients, chest radiograph in 46% of patients, urinalysis in 43% of patients, and funduscopy documented in 36% of patients. All studies were performed in 6% of patients and were associated with complaints of dyspnea (odds ratio [OR] 3.1; 95% confidence interval [CI] 1.1 to 8.7) and chest pain (OR 3.0; 95% CI 1.2 to 7.6). Oral antihypertensives were administered to 36% of patients and were associated with blood pressure-related complaints (OR 2.0 [1.2 to 3.3]), patient-suspected severely elevated blood pressure (OR 5.6, 95% CI 2.0 to 15.3), and being uninsured (OR 2.0; 95% CI 1.2 to 3.3). Intravenous antihypertensives were given to 4% of patients, associated only with chest pain (OR 3.2; 95% CI 1.1 to 9.5). Modification of antihypertensive regimen was documented in 19% of discharged patients and associated with patient-suspected severely elevated blood pressure (OR 5.5; 95% CI 2.5 to 12.2) and being uninsured (OR 1.8; 95% CI 1.1 to 2.9). CONCLUSION: The majority of ED patients with severely elevated blood pressure do not receive the evaluation, medical regimen modification, and discharge instructions advised by current guidelines. Further study is necessary to determine whether these recommendations are appropriate in this setting.

Behavioral risk factor and preventive health care practice survey of immigrants in the emergency department.

OBJECTIVE: To compare the demographic profiles, behavioral risk factors, and preventive health care practices of adult immigrant and non-immigrant patients while considering the effects of various socioeconomic variables. METHODS: This was a prospective survey administered at a large urban emergency department in New York City. Study subjects were adult immigrant patients presenting in an eight-week period in 1998. One non-immigrant control patient was recruited concurrently with every two immigrant patients. Differences between immigrants and non-immigrants were evaluated using the chi-square test. Multivariate logistic regression models were used to adjust for confounding variables. RESULTS: Eight hundred sixty-nine immigrant patients from 80 countries and 354 non-immigrant patients completed surveys. Immigrants were more likely not to have reached high school (28.9% vs 8.5%; p < 0.001), to have annual family incomes less than $20,000 (73.8% vs 64.5%; p < 0.01), and to have no health coverage (51.7% vs 30.8%; p < 0.001). Immigrant women were more likely never to have had a Papanicolaou test (16.1% vs 1.4%; OR 11.24, 95% CI = 2.70 to 46.8) and never to have performed a self-breast examination (20.8% vs 7.5%; OR 2.03, 95% CI = 1.29 to 3.20). Immigrants were more likely not to use condoms (63.4% vs 42.8%; OR 1.61, 95% CI = 1.20 to 2.15) and never to have visited a dentist (21.2% vs 7.8; OR 2.54, 95% CI = 1.60 to 4.04). Immigrants were more likely never to have received a purified protein derivative (PPD) skin test (30.3% vs 9.1%; OR 3.85, 95% CI = 2.56 to 5.80) and never to have received a tetanus immunization (48.1% vs 13.5%; OR 3.09, 95% CI = 2.17 to 4.42). These differences were independent of age, gender, marital status, employment, education, income, and health insurance status. When analyzing the immigrant group alone, region of origin, length of time in the United States, and English ability were significant independent predictors of higher-risk behavioral profiles and poor preventive health care practices. CONCLUSIONS: Differences exist between the socioeconomic profiles, behavioral risk profiles, and preventive health care practices of immigrant and non-immigrant patients presenting to a large inner-city municipal emergency department. Different populations within a heterogeneous group of immigrants have distinct health risks and public health needs.

Emergency physicians' perspectives on smallpox vaccination.

OBJECTIVE: To evaluate emergency physician (EP) attitudes toward smallpox vaccination, the treatment of patients with suspected smallpox, and the threat of a bioterrorist attack. METHODS: This was a prospective study utilizing a standardized survey instrument that was distributed on November 16, 2002, and collected by February 1, 2003. EPs from a sample of 50 accredited emergency medicine programs were surveyed regarding their perspectives on smallpox vaccination. RESULTS: A total of 989 surveys were collected from 42 emergency medicine programs. Of the respondents, 43.4% would currently volunteer for smallpox vaccination. EPs previously vaccinated against smallpox were 1.46 times more likely to volunteer for vaccination (95% CI = 1.14 to 1.93). EPs who believed they were at risk for complications were less than half as likely to volunteer for vaccination. EPs who perceived a significant risk of a bioterrorist attack were 2.7 times more likely to volunteer for the vaccine compared with those who thought the risk was minimal (95% CI = 2.06 to 3.47). Of the respondents, 34.4% believed the risks of the vaccination outweighed the benefits, 33% did not, and 32.6% were unsure. CONCLUSIONS: Currently, fewer than half of EPs surveyed would volunteer for smallpox vaccination. Factors associated with a willingness to be vaccinated include previous smallpox vaccination and the perceived threat of a bioterrorist attack. The variation in EP attitudes toward smallpox vaccination may be due to uncertain risk-to-benefit ratio. The opinions and actions of EPs may be influential on current and future government policy and public opinion.

Factors predictive of acute renal failure and need for hemodialysis among ED patients with rhabdomyolysis.

OBJECTIVE: We assessed the primary causes of rhabdomyolysis, the factors associated with the development of acute renal failure (ARF), and the need for hemodialysis (HD) among a series of patients presenting to an urban emergency department with rhabdomyolysis. METHODS: A chart review between January 1992 and December 1995 was conducted of patients aged 18 years or older with a diagnosis of rhabdomyolysis and an initial serum creatine phosphokinase greater than 1000 U/L. Patients were excluded if they had evidence of myocardial ischemia, cerebrovascular insufficiency, or the development of rhabdomyolysis after hospitalization. Demographic information, presumed causative factors, past medical history, medication usage, and laboratory data were collected. RESULTS: Ninety-seven patients (93 men, 4 women) were enrolled, with a mean age of 35.7 years. The most common causes of rhabdomyolysis were cocaine (30), exercise (29), and immobilization (18). Seventeen of 97 (17.5%) patients developed ARF; 8 patients (8.25%) needed HD. Several clinical and laboratory factors were statistically associated with development of ARF and need for HD. The only variable that was predictive of both ARF and need for HD in separate multivariate regression models was the initial creatinine (Cr). Initial blood urea nitrogen also was predictive of the need for HD. No patient developed ARF with an initial Cr less than 1.7 mg/dL. CONCLUSION: Acute renal failure and need for HD are common complications of rhabdomyolysis. Except for initial serum Cr and blood urea nitrogen, clinical and laboratory factors were not reliable predictors for the development of ARF or need for HD.

Elevated blood pressure in urban emergency department patients.

OBJECTIVES: There has been little systematic study of emergency department (ED) patients with elevated blood pressure (BP) values. The authors sought to characterize ED patients with elevated BP values, assess presenting symptoms, and determine the prevalence of elevated BP after discharge. METHODS: This was a cross-sectional study performed in four academic EDs. Adults presenting with systolic BP >or=140 mm Hg or diastolic BP >or=90 mm Hg were enrolled over a one-week equivalent period. Demographics, medical history, and symptoms were obtained by chart abstraction and structured interview. A random patient subset underwent a three-week follow-up interview. BP measurements were staged, using Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-VI) criteria, according to the greatest value noted in the ED. RESULTS: A total of 1,396 patients were enrolled. Stage 1 BP values were noted in 44.3%, stage 2 in 25.3%, and stage 3 in 30.3%. African American patients more frequently had stage 2 and 3 BP values than other ethnic groups. BP measurements were repeated in 61.1% of patients and were the same or greater in 51.3% of patients. Dyspnea was associated with greater BP values. Among the 63.9% of patients who were interviewed, 52.7% were not being treated for hypertension, and 42.1% of those with hypertension had recently missed a medication dose. Follow-up was obtained in 74.7% of those targeted. A visit to a medical practitioner since discharge was reported by 63.2%; of these, 26.1% reported that their BP remained elevated. CONCLUSIONS: Elevated BP is common among ED patients. African American patients are more likely than those of other ethnic groups to have greater BP values. The ED visit may be a good opportunity to identify patients with unrecognized or poorly controlled hypertension.

Utility of acetaminophen screening in unsuspected suicidal ingestions.

Acetaminophen (APAP) is a common overdosed medication. Because of the lack of specific symptoms associated with initial toxicity, potential unsuspected APAP toxicity is a concern in suicidal ingestions. To identify the likelihood of unsuspected APAP toxicity in suicidal ingestions, we performed a retrospective study of all suicidal ingestions without a history of APAP exposure reported to a poison control center over a 6-mo period. History, symptoms, and APAP levels to assessed the incidence of unsuspected APAP ingestions. In a total of 471 cases, 151 had APAP levels requested but not documented in our records. Of the remaining 320 cases, 23 (7.2%) had APAP levels > 10 microg/mL. Twelve patients were treated with Nacetylcysteine, 7 patients (2.2 %) had potentially toxic levels, and 5 patients had non-toxic or uninterpretable levels. Although the overall risk of unsuspected acetaminophen toxicity in suicidal ingestions is small, the definite risk in this treatable entity warrants universal APAP screening in all suicidal ingestions.