Patient Care

In the Literature: HM-Related Research You Need to Know


In This Edition

Literature at a Glance

A guide to this month’s studies

Characteristics of Community-Acquired methicillin-resistant Staphylococcus aureus Pneumonia in an Academic Medical Center

Clinical question: What are the clinical features and epidemiology of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) pneumonia?

Background: CA-MRSA is an emerging cause of pneumonia. The genetic makeup of most CA-MRSA strains is different than that of nosocomial MRSA. Typically, CA-MRSA is resistant to methicillin, beta-lactams, and erythromycin, but it retains susceptibility to trimethoprim-sulfamethoxazole (TMP/sulfa) and clindamycin.

In addition, the most common strain of CA-MRSA carries the Panton-Valentine leukocidin (PVL) toxin, which is associated with necrotizing pneumonia and high mortality rates.

Study design: Retrospective case series.

Setting: A 1,100-bed teaching hospital in Chicago.

Synopsis: Of the 5,955 discharges with a diagnosis-related group (DRG) code of pneumonia, 15 met criteria for CA-MRSA, or <1% of all inpatient community-acquired pneumonia cases. All 15 CA-MRSA strains were positive for PVL.

Seven of the 15 patients never were admitted to the ICU, while seven patients required mechanical ventilation. Seven patients were immunocompromised; one patient presented with preceding influenza; seven patients presented with hemoptysis; and eight patients demonstrated findings of lung necrosis on CT scan. Two patients died; both were immunocompromised.

Although the initial antibiotic regimen varied considerably, 14 patients ultimately received either clindamycin or linezolid.

Bottom line: CA-MRSA pneumonia is an uncommon subset of community-acquired pneumonia admissions. Approximately half the patients admitted with CA-MRSA presented with features of severe pneumonia. Nearly all were treated with antibiotics that inhibit exotoxin production, and the associated mortality rate of 13% was lower than previously reported.

Citation: Lobo JL, Reed KD, Wunderink RG. Expanded clinical presentation of community-acquired methicillin-resistant Staphylococcus aureus pneumonia. Chest. 2010;138(1):130-136.

Clinical Shorts


Retrospective case review of 168 patients treated with IV aspirin in a large European hospital for severe, mostly medication rebound, headaches showed that 85% of patients had a moderate or good response to treatment. Side effects occurred in 5.9% of patients and were all considered minor.

Citation: Weatherhall MW, Telzerow AJ, Cittadini E, Kaube H, Goadsby PJ. Intravenous aspirin (lysine acetylsalicylate) in the inpatient management of headache. Neurology. 2010;75(12):1098-1103.


Surveys of inpatients and the resident and attending physicians caring for them demonstrated widely differing perceptions between the groups regarding patient knowledge of doctor in charge, primary diagnosis, and new medications or potential side effects.

Citation: Olson DP, Windish DM. Communication discrepancies between physicians and hospitalized patients. Arch Intern Med. 2010;170(15):1302-1307.

Gurgling Breath Sounds in Hospitalized Patients Might Predict Subsequent Pneumonia Development

Clinical question: Can gurgling sounds over the glottis during speech or quiet breathing predict hospital-acquired pneumonia (HAP)?

Background: HAP is a relatively frequent complication of hospitalization. HAP usually portends an increase in morbidity and mortality. Patients in the hospital might have disease states that inhibit the reflexes that normally eliminate secretions from above or below their glottis, increasing the risk of pneumonia.

Study design: Prospective cohort.

Setting: A 350-bed community teaching hospital in Bridgeport, Conn.

Synopsis: All patients admitted to a respiratory-care unit and general medical ward from December 2008 to April 2009 underwent auscultation over their glottis by study personnel. Patients with gurgles heard during speech or quiet breathing on auscultation and patients without gurgles were entered into the study in a 1:3 fashion, until 20 patients with gurgles and 60 patients without gurgles had been enrolled. Patients were followed for the development of clinical and radiographic evidence of HAP, ICU transfer, and in-hospital death.

Both dementia and treatment with opiates were independent predictors of gurgle in multivariate analysis. HAP occurred in 55% of the patients with gurgle versus 1.7% of patients without gurgle. In addition, 50% of the patients with gurgle required transfer to the ICU, compared with only 3.3% of patients without gurgle. In-hospital mortality was 30% among patients with gurgle versus 11.7% among patients without gurgle.

Bottom line: In patients admitted to the medical service of a community teaching hospital, gurgling sounds heard over the glottis during speech or quiet inspiration are independently associated with the development of HAP, ICU transfer, and in-hospital mortality.

Citation: Vazquez R, Gheorghe C, Ramos F, Dadu R, Amoateng-Adjepong Y, Manthous CA. Gurgling breath sounds may predict hospital-acquired pneumonia. Chest. 2010;138(2):284-288.

Treatment of Active Ulcerative Colitis with Triple Antibiotic Therapy Provides Better Response than Placebo

Clinical question: Does combination antibiotic therapy induce and/or maintain remission of active ulcerative colitis (UC)?

Background: Mouse models and other experimental evidence have suggested a pathogenic role for microbes in the development and/or exacerbation of ulcerative colitis, although antibiotic human trials have produced conflicting results. Recently, Fusobacterium varium was shown to be present in the gastrointestinal (GI) tract of most UC patients, and a pilot study using targeted antibacterials demonstrated efficacy in treating active UC.

Study design: Randomized, double-blind, placebo-controlled, multicenter trial.

Setting: Eleven hospitals in Japan.

Synopsis: Patients with mild to severe chronic relapsing UC were randomly assigned to either combination antibiotic therapy or placebo. All previous UC treatment regimens were continued in study patients, with the exception of steroids, which were tapered slowly if possible. Patients in the antibiotic group received a two-week combination therapy of amoxicillin, tetracycline, and metronidazole. Patients were followed weekly or monthly and underwent periodic exams and colonoscopies to assess clinical and endoscopic improvement for 12 months.

One hundred five patients were enrolled in each group. The clinical response rate at one year in patients treated with antibiotics was 44.8% versus 22.8% in the placebo group. Remission at one year was achieved in 26.7% of patients treated with antibiotics versus 14.9% of placebo patients. Endoscopic response rates and steroid discontinuation rates were higher in the antibiotic-treated groups. Effects were most pronounced in the group of patients with active disease.

Bottom line: Triple antibiotic therapy with amoxicillin, tetracycline, and metronidazole, when compared with placebo, was associated with improvement in clinical symptoms, endoscopic findings, remission rates, and steroid withdrawal in patients with active ulcerative colitis.

Citation: Ohkusa T, Kato K, Terao S, et al. Newly developed antibiotic combination therapy for ulcerative colitis: a double-blind placebo-controlled multicenter trial. Am J Gastroenterol. 2010;105(8):1820-1829.

Clinical Shorts


This large, retrospective cohort study of nearly 20,000 patients across 375 U.S. centers found no difference, after multivariate adjustment, between macrolides and quinolones across a variety of outcomes: treatment failure, adjusted length of stay, or adjusted cost. Curiously, diarrhea was more common with quinolones.

Citation: Rothberg MB, Pekow PS, Lahti M, Brody O, Skiest DJ, Lindenauer PK. Comparative effectiveness of macrolides and quinolones for patients hospitalized with acute exacerbations of chronic obstructive pulmonary disease (AECOPD). J Hosp Med. 2010;5(5):261-267.


This study reviewed four different methods of measuring proteinuria in 700 patients: 24-hour urine albumin excretion, 24-hour urine protein excretion, first-morning void urine albumin concentration, and first-morning void urine albumin-to-creatinine ratio. The first morning void urine albumin-to-creatinine ratio offered the strongest predictor of subsequent doubling of serum creatinine or progression to end-stage renal disease.

Citation: Lambers Heerspink HJ, Gansevoort RT, Brenner BM, et al. Comparison of different measures of urine protein excretion for prediction of renal events. J Am Soc Nephrol. 2010;21(8):1355-1360.

Early TIPS Outperformed Optimal Medical Therapy in Patients with Advanced Cirrhosis and Variceal Bleeding

Clinical question: Does early treatment with a transjugular intrahepatic portosystemic shunt (TIPS) improve outcomes in patients with advanced cirrhosis and variceal bleeding?

Background: Current management guidelines for variceal bleeding include treatment with vasoactive drugs and serial endoscopy, yet treatment failure occurs in 10% to 15% of patients. TIPS is highly effective in controlling bleeding in such patients, but it historically has been reserved for patients who repeatedly fail preventive strategies.

Study design: Randomized controlled trial.

Setting: Nine European centers.

Synopsis: Sixty-three patients with advanced cirrhosis and acute esophageal variceal bleeding treated with optimal medical therapy were randomized within 24 hours of admission to either 1) early TIPS (polytetrafluoroethylene-covered stents) within 72 hours of randomization, or 2) ongoing optimal medical therapy with vasoactive drugs, treatment with a nonselective beta-blocker, and endoscopic band ligation.

During the median 16-month follow-up, rebleeding or failure to control bleeding occurred in 45% of patients in the optimal medical therapy group versus 3% of patients in the early TIPS group. One-year actuarial survival was 61% in the optimal medical therapy group versus 86% in the early-TIPS group. Remarkably, encephalopathy was less common in the early-TIPS group, and adverse events as a whole were similar in both groups.

Bottom line: Early use of TIPS was superior to optimal medical therapy for patients with advanced cirrhosis hospitalized for acute variceal bleeding at high risk for treatment failure.

Citation: García-Pagán JC, Caca K, Bureau C, et al. Early use of TIPS in patients with cirrhosis and variceal bleeding. N Engl J Med. 2010;362(25):2370-2379.

Low-Dose Oral Corticosteroids As Effective As High-Dose Intravenous Therapy in COPD Exacerbations

Clinical question: In patients hospitalized with acute exacerbation of chronic obstructive pulmonary disease (COPD), what are the outcomes of those initially treated with low doses of steroids administered orally compared with those initially treated with higher doses intravenously?

Background: COPD affects 6% of adults in the U.S., and acute exacerbation of COPD is one of the leading causes of hospitalization nationwide. Systemic corticosteroids are beneficial for patients hospitalized with acute exacerbation of COPD; however, optimal dose and route of administration are uncertain.

Study design: Retrospective cohort.

Setting: Four hundred fourteen U.S. acute-care hospitals; most were small to midsize nonteaching facilities serving urban patient populations.

Synopsis: Almost 80,000 patients admitted to a non-ICU setting with a diagnosis of acute exacerbation of COPD from 2006 to 2007, and who received systemic corticosteroids during the first two hospital days, were included in the study. In contrast to clinical guidelines recommending the use of low-dose oral corticosteroids, 92% of study participants were treated initially with intravenous steroids, whereas 8% received oral treatment. The primary composite outcome measure—need for mechanical ventilation after the second hospital day, inpatient mortality, or readmission for COPD within 30 days—was no worse in patients treated with oral steroids. Risk of treatment failure, length of stay, and cost were significantly lower among orally treated patients.

Bottom line: High-dose intravenous steroids appear to be no more effective than low-dose oral steroids for acute exacerbation of COPD. The authors recommend a randomized controlled trial be conducted to compare these two management strategies.

Citation: Lindenauer PK, Pekow PS, Lahti MC, Lee Y, Benjamin EM, Rothberg MB. Association of corticosteroid dose and route of administration with risk of treatment failure in acute exacerbation of chronic obstructive pulmonary disease. JAMA. 2010;303(23):2359-2367.

Clinical Short


In this case-control study of a cohort of elderly patients 66 years or older receiving continuous ACE inhibitor (ACEI) or angiotensin II receptor blocker (ARB) therapy, use of trimethoprim-sulfamethoxazole was associated with a sevenfold increased risk of hyperkalemia-associated hospitalization compared with amoxicillin.

Citation: Antoniou T, Gomes T, Juurlink DN, Loutfy MR, Glazier RH, Mamdani MM. Trimethoprim-sulfamethoxazole-induced hyperkalemia in patients receiving inhibitors of the renin-angiotensin system: a population-based study. Arch Intern Med. 2010;170(12):1045-1049.

Reminders and Stop Orders Reduce Catheter-Associated Urinary Tract Infections

Clinical question: Do interventions that remind clinicians of the presence of urinary catheters and prompt timely removal decrease the rate of catheter-associated urinary tract infections (CA-UTI)?

Background: CA-UTI is a common yet preventable hospital-acquired infection. Many catheters are placed unnecessarily, remain in use without physician awareness, and are not removed promptly when no longer needed.

Study design: Systematic review and meta-analysis of 13 preintervention and postintervention quasi-experimental trials and one randomized controlled trial.

Setting: Studies conducted in the U.S., Canada, Europe, and Asia.

Synopsis: This literature search revealed 14 articles that used a reminder or stop-order intervention to prompt removal of urinary catheters and reported pre- and postintervention outcomes for CA-UTI rates, duration of urinary catheter use, and recatheterization need. Five studies used stop orders and nine studies used reminder interventions.

Use of a stop order or reminder reduced the rate of CA-UTI (episodes per 1,000 catheter days) by 52%. Mean duration of catheterization decreased by 37%, which resulted in 2.61 fewer days of catheterization per patient in the intervention versus control groups. Recatheterization rates were similar in the control and intervention groups.

Bottom line: Urinary catheter reminders and stop orders are low-cost strategies that appear to reduce the rate of CA-UTI.

Citation: Meddings J, Rogers MA, Macy M, Saint S. Systematic review and meta-analysis: reminder systems to reduce catheter-associated urinary tract infections and urinary catheter use in hospitalized patients. Clin Infect Dis. 2010;51(5):550-560.

Chest-Compression-Only Bystander CPR Increases Survival

Clinical question: Is bystander cardiopulmonary resuscitation (CPR) with chest compressions alone or chest compressions with rescue breathing superior in out-of-hospital adult cardiac arrest?

Background: Out-of-hospital cardiac arrest claims hundreds of thousands of lives each year. Early initiation of CPR by a layperson can increase a patient’s chances of surviving and having a favorable long-term neurologic recovery. Although traditional CPR consists of chest compression with rescue breathing, chest compression alone might be more acceptable to many laypersons and has the potential advantage of fewer compression interruptions.

Study design: Multicenter randomized trial.

Setting: Two EMSs in Washington state and one in London.

Synopsis: Patients were initially eligible for this study if a dispatcher determined that the patient was unconscious and not breathing, and that bystander CPR was not yet under way. If the caller was willing to undertake CPR with the dispatcher’s assistance, a randomization envelope containing CPR instructions was opened. Patients with arrest due to trauma, drowning, or asphyxiation were excluded, as were those under 18 years of age.

No significant difference was observed between the two groups in the percentage of patients who survived to hospital discharge or who survived with a favorable neurologic outcome. However, subgroup analyses showed a trend toward a higher percentage of patients surviving to hospital discharge with chest compressions alone, as compared with chest compressions with rescue breathing for patients with a cardiac cause of arrest and for those with shockable rhythms.

Bottom line: Dispatcher CPR instruction consisting of chest compression alone was noninferior to conventional CPR with rescue breathing, and it showed a trend toward better outcomes in cardiac cause of arrest.

Citation: Rea TD, Fahrenbruch C, Culley L, et al. CPR with chest compression alone or with rescue breathing. N Engl J Med. 2010;363(5):423-433.

Low Albumin Is Associated with Postoperative Wound Infections

Clinical question: What is the relationship between preoperative serum albumin levels and postoperative surgical-site infections (SSI)?

Background: Poor nutritional status is associated with adverse surgical outcomes. Serum albumin can both reflect nutritional status and function as a negative acute phase reactant, i.e., decreases in the setting of inflammation. It is uncertain whether low preoperative albumin levels are associated with postoperative SSI risk.

Study design: Retrospective cohort with multivariate analysis.

Setting: Four centers in Ireland.

Synopsis: Patients undergoing GI surgery (n=524) were prospectively followed as part of an SSI database. Demographic data, American Society of Anesthesia class, serum albumin levels, and presence and severity of SSI data were collected on all patients. Follow-up extended to 30 days.

SSI developed in 20% of patients. Patients who developed a SSI had lower serum albumin levels (mean 3.0 g/dL versus 3.6 g/dL). A serum albumin level less than 3.0 g/dL was associated with greater risk of SSI (relative risk 5.68), deeper SSI, and prolonged length of stay.

Bottom line: After controlling for other variables, serum albumin lower than 3.0 g/dL is independently associated with SSI frequency and severity.

Citation: Hennessey DB, Burke JP, Ni-Dhonochu T, Shields C, Winter DC, Mealy K. Preoperative hypoalbuminemia is an independent risk factor for the development of surgical site infection following gastrointestinal surgery: a multi-institutional study. Ann Surg. 2010;252 (2):325-329. TH

Pediatric HM Literature

Nebulized Hypertonic Saline Alone Safe to Study in Bronchiolitis

Reviewed by Pediatric Editor Mark Shen, MD, medical director of hospital medicine at Dell Children’s Medical Center, Austin, Texas.

Clinical question: Is nebulized 3% saline solution safe to use alone in infants with bronchiolitis?

Background: Nebulized 3% (hypertonic) saline is increasingly used in the treatment of infants hospitalized with bronchiolitis. Studies to date have primarily investigated its efficacy in conjunction with bronchodilators due to a theoretical risk of bronchospasm. The safety profile of hypertonic saline alone in bronchiolitis is unknown.

Study design: Retrospective cohort study.

Setting: A single children’s hospital.

Synopsis: An existing QI database was reviewed during one winter season. One hundred fifty-four records were analyzed, comprising previously healthy infants with acute bronchiolitis. Hypertonic (3%) saline delivered more than four hours before and after albuterol was considered to have been given alone. Adverse events were not defined a priori, and documentation of symptoms related to medication administration was encouraged via a new comment section of a pathway scoring system.

Sixty-eight patients received 444 doses of hypertonic saline, 377 (85%) of which were administered alone. Four adverse events (1.0%) occurred in the group without adjunctive bronchodilator therapy; one adverse event (1.1%) occurred after concomitant delivery of albuterol and 3% saline. Rates of readmission and transfer to higher level of care were similar between those that did and did not receive hypertonic saline.

The potential for under-ascertainment of adverse events is significant with the retrospective design and frequency of underreporting in most hospitals. In addition, adverse events related to medication administration might be particularly difficult to assess in such dynamic diseases as bronchiolitis. Nevertheless, this study does suggest that adverse event rates are low with hypertonic saline alone, paving the way for future studies to assess its efficacy without bronchodilators clouding the picture.

Bottom line: Nebulized 3% saline has a low rate of adverse events in infants with acute bronchiolitis.

Citation: Ralston S, Hill V, Martinez M. Nebulized hypertonic saline without adjunctive bronchodilators for children with bronchiolitis. Pediatrics. 2010;126(3):e520-e525.

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