Subtherapeutic linezolid concentrations in a patient with morbid obesity and methicillin-resistant Staphylococcus aureus pneumonia: case report and review of the literature.

OBJECTIVE: To report a case of subtherapeutic linezolid concentrations in a patient with morbid obesity. CASE SUMMARY: A 34-year-old male with morbid obesity (265 kg, body mass index 82 kg/m(2)) was admitted for severe sepsis due to respiratory failure requiring emergent intubation and treatment of community-acquired pneumonia. Admission tracheal aspirate culture revealed methicillin-resistant Staphylococcus aureus (MRSA) for which vancomycin was prescribed. Therapy subsequently was changed to linezolid, because the patient's clinical status worsened, with significant hypoxia (partial pressure of arterial oxygen/fraction of inspired oxygen [PaO2/FiO2] ratio 145), increasing leukocytosis (white blood cell count from 10,800/µL on admission to 15,400/µL on hospital day 6), and persistent fever (38.3 °C). After 48 hours of linezolid monotherapy, the patient remained febrile with continued leukocytosis, worsening hypoxemia, and a persistently positive MRSA culture from a repeat endotracheal aspirate. Linezolid serum concentrations were obtained and vancomycin was reinstituted, after which the patient began to improve (afebrile, improving PaO2/FiO2 ratio, decreasing leukocytosis). On hospital day 12, the patient removed his endotracheal tube, and a sputum sample was obtained for culture. The patient's clinical status subsequently declined, prompting addition of cefepime to his antibiotic regimen. This sputum culture revealed not only MRSA, but also quinolone-resistant Escherichia coli. After completing treatment for both organisms the patient was discharged home. DISCUSSION: Limited data on linezolid dosing in the morbidly obese population show lower serum drug concentrations than those in nonobese patients, but no clinical failure has been reported when treating MRSA skin and soft tissue infections or MRSA tracheitis. In our patient, low steady-state linezolid serum concentrations (peak 4.13 µg/mL [reference 15-27] and trough 1.27 µg/mL [reference 2-9]) were thought to contribute to his poor clinical response. CONCLUSIONS: To our knowledge, this is the first report of subtherapeutic linezolid concentrations correlated with decreased clinical effectiveness when during treatment of MRSA pneumonia in a patient with morbid obesity.

Association between meeting core elements for inpatient antimicrobial stewardship and antibiotic utilization.

We used multivariable analyses to assess whether meeting core elements was associated with antibiotic utilization. Compliance with 7 elements versus not doing so was associated with higher use of broad-spectrum agents for community-acquired infections [days of therapy per 1,000 patient days: 155 (39) vs 133 (29), P = .02] and anti-methicillin-resistant S. aureus agents [days of therapy per 1,000 patient days: 145 (37) vs 124 (30), P = .03].

The impact of formulary restriction on the relative consumption of carbapenems in intensive care units at an academic medical center.

Antipseudomonal carbapenems are an important target for antimicrobial stewardship programs. We evaluated the impact of formulary restriction and preauthorization on relative carbapenem use for medical and surgical intensive care units at a large, urban academic medical center using interrupted time-series analysis.

Antimicrobial stewardship practices in Virginia.

The Society of Healthcare Epidemiology of America, the Centers for Disease Control and Prevention, and the President's Council of Advisors on Science and Technology recognize the need to combat antimicrobial resistance through the promotion of antimicrobial stewardship programs. Health care facilities in Virginia were surveyed using a 23-item survey focused on facility characteristics and antimicrobial stewardship strategies. Antimicrobial stewardship activities were highly variable and many are missing key personnel and resources.

Dapsone-induced sulfone syndrome.

OBJECTIVE: To report a patient with dapsone-induced sulfone syndrome. CASE SUMMARY: A 42-year-old HIV-infected African American man developed fever, lymphadenopathy, exfoliative dermatitis, hepatitis, and methemoglobinemia 4 weeks after starting dapsone. Complete resolution of symptoms and laboratory abnormalities occurred with cessation of dapsone therapy. DISCUSSION: Sulfone syndrome is not a well-known sequela of dapsone therapy. It is not dose-related, usually occurs in doses of 50-300 mg/d, all cases occur within 2 months of starting dapsone, all patients have fever, and most patients will develop rash and evidence of hepatic injury. The temporal relationship between dapsone therapy and onset of clinical symptoms and objective data led us to believe that dapsone caused sulfone syndrome in our patient. An objective causality assessment revealed that the adverse drug event was probable. CONCLUSIONS: Although sulfone syndrome appears to be relatively uncommon, healthcare practitioners must be aware of the potentially fatal syndrome associated with dapsone use.