David J. Karras

Chest Pain Associated With Cocaine: An Assessment of Prevalence in Suburban and Urban Emergency Departments

STUDY OBJECTIVE Chest pain and myocardial infarction following the use of cocaine have been well documented. We assessed the prevalence of cocaine use in patients who presented to the emergency department with chest pain of possibly ischemic origin. DESIGN During times of research assistant availability, consecutive adults with the chief complaint of chest pain unexplained by trauma or radiographic abnormality were questioned about cocaine use in the preceding week. Urine was tested for the presence of cocaine or cocaine metabolites with a highly accurate bedside urine test kit (specificity, 100%; sensitivity 98%). Anonymous unlinked data-collection methods were used. Therefore we could not determine whether the patients who used cocaine had sustained myocardial infarctions. SETTING One suburban and three urban EDs. RESULTS We enrolled 359 patients with a mean age of 51 years, 8% of whom sustained myocardial infarctions. Sixty patients (17%) had cocaine or cocaine metabolites in urine. The likelihood of testing positive for cocaine varied by age group: 18 to 30 years, 29%; 31 to 40 years, 48%; 41 to 50 years, 18%; 51 to 60 years, 3%; 61 years or older, 0% (P < .0001). Of the 60 patients who tested positive for cocaine, only 43 (72%) admitted recent use. CONCLUSION Many ED patients with chest pain have recently used cocaine. Because the recent use of cocaine is not uncommon in patients with chest pain up to 60 years old, such patients should be questioned about cocaine use. When treatment or disposition may be altered, consideration should be given to objective assessment of cocaine use because patient self-report does not appear reliable.

Poisoning from “Spanish fly” (cantharidin)

Cantharidin, known popularly as Spanish fly, has been used for millennia as a sexual stimulant. The chemical is derived from blister beetles and is notable for its vesicant properties. While most commonly available preparations of Spanish fly contain cantharidin in negligible amounts, if at all, the chemical is available illicitly in concentrations capable of causing severe toxicity. Symptoms of cantharidin poisoning include burning of the mouth, dysphagia, nausea, hematemesis, gross hematuria, and dysuria. Mucosal erosion and hemorrhage is seen in the upper gastrointestinal (GI) tract. Renal dysfunction is common and related to acute tubular necrosis and glomerular destruction. Priapism, seizures, and cardiac abnormalities are less commonly seen. We report four cases of cantharidin poisoning presenting to our emergency department with complaints of dysuria and dark urine. Three patients had abdominal pain, one had flank pain, and the one woman had vaginal bleeding. Three had hematuria and two had occult rectal bleeding. Low-grade disseminated intravascular coagulation, not previously associated with cantharidin poisoning, was noted in two patients. Management of cantharidin poisoning is supportive. Given the widespread availability of Spanish fly, its reputation as an aphrodisiac, and the fact that ingestion is frequently unwitting, cantharidin poisoning may be a more common cause of morbidity than is generally recognized. Cantharidin poisoning should be suspected in any patient presenting with unexplained hematuria or with GI hemorrhage associated with diffuse injury of the upper GI tract.

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.).

Endogenous mediators in emergency department patients with presumed sepsis: Are levels associated with progression to severe sepsis and death?

STUDY OBJECTIVE We sought to determine whether levels of the endogenous mediators tumor necrosis factor (TNF)-alpha, interleukin (IL) 6, and nitric oxide (NO) measured in patients with presumed sepsis (systemic inflammatory response syndrome [SIRS] and infection) are different than levels in patients with presumed noninfectious SIRS, whether levels are associated with septic complications, and whether there are potential relationships between mediators. METHODS A prospective, observational tricenter study of a convenience sample of adults presenting to the emergency department meeting Bones criteria for SIRS (any combination of fever or hypothermia, tachycardia, tachypnea, or WBC count aberration) was performed. Mediator levels were determined and associated with deterioration to severe sepsis (hypotension, hypoperfusion, or organ dysfunction) and death in subjects admitted to the hospital with presumed sepsis. RESULTS One hundred eighty subjects with SIRS were enrolled and classified into 3 groups: group 1 (SIRS, presumed infection, admitted; n=108), group 2 (SIRS, presumed infection, discharged; n=27), and group 3 (SIRS, presumed noninfectious, admitted; n=45). Group 1 TNF-alpha and IL-6 levels were significantly higher than those found in the other groups. NO levels for groups 1 and 2 were significantly lower than those for group 3. TNF-alpha and IL-6 levels were higher in the group 1 subjects who had bacteremia or progressed to severe sepsis or death. NO levels were not associated with these outcomes. CONCLUSION ED patients admitted with presumed sepsis have elevated cytokine levels compared with patients with sepsis who are discharged and with those patients with presumed noninfectious SIRS. An association appears to exist between cytokines and subsequent septic complications in these patients. The importance of these measures as clinical predictors for the presence of infection and subsequent septic complications needs to be evaluated.

Guidelines reduce X-ray and blood gas utilization in acute asthma

Using a retrospective chart review, we compared the use of chest radiography (CXR) and arterial blood gas testing (ABG) before (pre-P) and after (post-P) initiation of specific ordering guidelines for the use of these studies for patients presenting to the ED with acute asthma exacerbation. We noted the number of tests performed, the indication for the test, and the results when performed. There was a 55% reduction in the number of chest radiographs (85 of 213 patients pre-P had CXR as compared with 40 of 222 patients post-P, P <.001). Of the patients who did not have a chest x-ray in the ED, none had an abnormal chest x-ray obtained after admission or if they returned to the ED within 72 hours. There was a 57% reduction in the number of arterial blood gases post-P (9 of 222 patients) as compared with pre-P (20 of 213 patients, P <.001). Although patients with abnormal ABGs had a discernible indication for testing, all of the ABGs for which no indication could be found were normal. A protocol containing criteria for obtaining chest x-rays and arterial blood gas testing can reduce the use of diagnostic testing, thereby improving ED efficiency without adversely impacting patient care.

Absolute Lymphocyte Count as a Predictor of CD4 Count

STUDY OBJECTIVE To determine whether the absolute lymphocyte count (ALC) (white blood count x lymphocyte percentage) can be used to predict a low CD4 count. METHODS We conducted a retrospective data analysis of consecutive CD4 count analyses performed between January 1, 1995, through December 1, 1995, at an urban university teaching hospital. Results of consecutive CD4 counts and simultaneously measured ALCs were analyzed from samples obtained in inpatient, clinic, and emergency department settings. The ability of ALC to predict a CD4 count less than 200 cells/mm3 was analyzed by calculating sensitivities, specificities, predictive values, and likelihood ratios for a range of ALC values. RESULTS Among the 807 samples, 322 results (40%) had a CD4 count less than 200 cells/mm3. The ALC and CD4 count were correlated (r=.69, P<.0001). An ALC less than 1,000 cells/mm3 predicted CD4 counts less than 200 cells/mm3 with a sensitivity of .67 (95% confidence interval .62 to .72), specificity of .96 (.94 to .98), positive predictive value of .91 (.87 to .95), and a negative predictive value of .81 (.78 to .84). An ALC less than 2,000 cells/mm3 predicted CD4 counts less than 200 cells/mm3 with a sensitivity of .97 (.95 to .99), specificity of .41 (.37 to .45), positive predictive value of .52 (.48 to .56), and negative predictive value of .95 (.92 to .98). CONCLUSION A reliable relationship exists between ALC and CD4 count. In a similar population, an ALC less than 1,000 cells/mm3 is predictive of a CD4 count less than 200 cells/mm3, and an ALC greater than or equal to 2,000 cells/mm3 is predictive of a CD4 count greater than or equal to 200 cells/mm3. Physicians may find these criteria useful in identifying patients with increased risk of opportunistic infection.

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.

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, &bgr;-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

Severe low back pain secondary to acute interstitial nephritis following administration of ranitidine

Acute interstitial nephritis is a disease characterized by renal inflammation and is thought to be secondary to a hypersensitivity reaction. Although the causes of acute interstitial nephritis are numerous, adverse reactions to many common drugs, particularly antibiotics and nonsteroidal anti-inflammatory agents, are important etiological factors. Acute interstitial nephritis has many clinical manifestations, most notably fever and rash. Flank pain is an uncommon presentation. A case of acute, severe, low-back pain and rash in a healthy woman found to be secondary to acute interstitial nephritis is reported. The etiology of acute interstitial nephritis in this patients case is suspected to be ranitidine (Zantac; Glaxo Pharmaceuticals, Research Triangle Park, NC), which has not been previously associated with this syndrome.

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.