Systematic overdosing of oxa- and cloxacillin in severe infections treated in ICU: risk factors and side effects.

BACKGROUND: Oxacillin and cloxacillin are the most frequently used penicillins for the treatment of severe methicillin-susceptible Staphylococcus aureus infections in intensive care units (ICUs), especially endocarditis. International recommendations do not suggest any adaptation of the dosage in case of renal impairment. We wanted to assess the risk factors for overdosing in ICU and the related observed side effects. METHODS: All patients with a therapeutic drug monitoring of oxa- or cloxacillin between 2008 and 2014 were included. The target range of trough concentration for total antibiotic activity was considered to be 20-50 mg/L. Data concerning the infection, the given treatment, the renal function, and the attributed side effects of overdosing were collected. A logistic regression model was used to compute the measured trough concentrations. RESULTS: Sixty-two patients were included in this study. We found a median trough plasma concentration of 134.3 mg/L (IQR 65.3-201 mg/L). Ten patients (16.1%) reached the target concentration; all other patients (83.9%) were overdosed. Eleven patients (17.7%) experienced neurological side effects attributed to a high antibiotic concentration, i.e. persistent coma and delirium. When adjusted on the dosage used, the risk of overdosing was significantly associated with a creatinine clearance <10 mL/min (with or without hemodialysis). CONCLUSION: With the suggested dose of 12 g/day for cloxacillin treatment in case of endocarditis and severe infections occurring in ICU, 83.9% of patients are largely overdosed. Considering the observed side effects, doses should be accurately monitored and reduced, particularly when renal replacement therapy is needed.

Viral-bacterial coinfection affects the presentation and alters the prognosis of severe community-acquired pneumonia.

BACKGROUND: Multiplex polymerase chain reaction (mPCR) enables recovery of viruses from airways of patients with community-acquired pneumonia (CAP), although their clinical impact remains uncertain. METHODS: Among consecutive adult patients who had undergone a mPCR within 72 hours following their admission to one intensive care unit (ICU), we retrospectively included those with a final diagnosis of CAP. Four etiology groups were clustered: bacterial, viral, mixed (viral-bacterial) and no etiology. A composite criterion of complicated course (hospital death or mechanical ventilation > 7 days) was used. A subgroup analysis compared patients with bacterial and viral-bacterial CAP matched on the bacterial pathogens. RESULTS: Among 174 patients (132 men [76 %], age 63 [53-75] years, SAPSII 38 [27;55], median PSI score 106 [78;130]), bacterial, viral, mixed and no etiology groups gathered 46 (26 %), 53 (31 %), 45 (26 %) and 30 (17 %) patients, respectively. Virus-infected patients displayed a high creatine kinase serum level, a low platelet count, and a trend toward more frequent alveolar-interstitial infiltrates. A complicated course was more frequent in the mixed group (31/45, 69 %), as compared to bacterial (18/46, 39 %), viral (15/53, 28 %) and no etiology (12/30, 40 %) groups (p < 0.01). In multivariate analysis, the mixed (viral-bacterial) infection was independently associated with complicated course (reference: bacterial pneumonia; OR, 3.58; CI 95 %, 1.16-11; p = 0.03). The subgroup analysis of bacteria-matched patients confirmed these findings. CONCLUSIONS: Viral-bacterial coinfection during severe CAP in adults is associated with an impaired presentation and a complicated course.

Early-onset status epilepticus in patients with acute encephalitis.

Status epilepticus (SE) is a common complication of acute encephalitis, but its determinants and prognostic value in this setting are not known.Risk factors for early-onset SE (within 48 hours of intensive care unit [ICU] admission) in consecutive adult patients with all-cause encephalitis admitted to the medical ICU of a university hospital (1991-2013) were evaluated by multivariate logistic regression analysis. To examine the prognostic value of SE, patients were classified into 3 groups: no SE, nonrefractory SE (NRSE), and refractory SE (RSE). Poor neurologic outcome was defined by a modified Rankin score of 4 to 6.Among the 290 patients, 58 (20%, 95% CI: 15%-25%) developed early-onset SE, comprising 44 patients with NRSE and 14 patients with RSE. Coma (adjusted odds ratio [OR]: 3.1, 95% CI: 1.5-6.3), cortical lesions on neuroimaging (adjusted OR: 3.7, 95% CI: 1.8-7.8), and nonneurologic organ failure(s) (adjusted OR: 13.6, 95% CI: 4.9-37.7) were found to be independent risk factors for SE. By contrast, a bacterial etiology had a protective effect (adjusted OR: 0.3, 95% CI: 0.1-0.7). Age, body temperature, and blood sodium levels were not independently associated with SE. Poor neurologic outcomes were observed at day 90 in respectively 23% (95% CI: 17%-28%), 23% (95% CI: 10%-35%), and 71% (95% CI: 48%-95%) of no SE, NRSE, and RSE patients (P < 0.01). After adjusting for confounders, RSE, but not NRSE, remained independently associated with 90-day mortality (adjusted OR: 6.0, 95% CI: 1.5-23.3).Coma, cortical involvement on neuroimaging, and nonneurologic organ failure(s) are independent risk factors for SE in patients with acute encephalitis. Conversely, a bacterial etiology is associated with a lower risk of SE.These findings may help identify patients who may benefit from prophylactic antiepileptic drugs.

Treatment of bloodstream infections in ICUs.

Bloodstream infections (BSIs) are frequent in ICU and is a prognostic factor of severe sepsis. Community acquired BSIs usually due to susceptible bacteria should be clearly differentiated from healthcare associated BSIs frequently due to resistant hospital strains. Early adequate treatment is key and should use guidelines and direct examination of samples performed from the infectious source. Previous antibiotic therapy knowledge, history of multi-drug resistant organism (MDRO) carriage are other major determinants of first choice antimicrobials in heathcare-associated and nosocomial BSIs. Initial antimicrobial dose should be adapted to pharmacokinetic knowledge. In general, a high dose is recommended at the beginning of treatment. If MDRO is suspected combination antibiotic therapy is mandatory because it increase the spectrum of treatment. Most of time, combination should be pursued no more than 2 to 5 days.Given the negative impact of useless antimicrobials, maximal effort should be done to decrease the antibiotic selection pressure. De-escalation from a broad spectrum to a narrow spectrum antimicrobial decreases the antibiotic selection pressure without negative impact on mortality. Duration of therapy should be shortened as often as possible especially when organism is susceptible, when the infection source has been totally controlled.

Ventilator-associated pneumonia due to carbapenem-resistant Gram-negative bacilli in an intensive care unit without carbapenemase-producing Enterobacteriaceae or epidemic Acinetobacter baumannii.

Risk factors for ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Gram-negative bacilli (CR-GNB) have rarely been evaluated in intensive care units (ICU) without epidemic carbapenemase-producing Acinetobacter baumannii or Enterobacteriaceae. We addressed this issue in a cohort of 141 patients (previous antimicrobial exposure, n = 131) with a first episode of VAP in a medico-surgical ICU. Twenty-six VAP (18.4%) involved a CR-GNB (Pseudomonas aeruginosa, n = 14, Stenotrophomonas maltophilia, n = 11, and A. baumannii, n = 1), without previous carbapenem exposure in 12 (46.1%) cases. GNB resistant to all ß-lactams except carbapenems were equally isolated in CR-GNB VAP (co-infections, 23%) and other episodes (30%). Previous exposure to aminoglycosides (odds ratio (OR) 1.14 per day, 95% confidence interval (CI) 1.02-1.30, p = 0.02) and the number of antimicrobial classes used before VAP (OR 1.38 per class, 95% CI 1.10-1.73, p = 0.006) were the only independent predictors of CR-GNB. These results suggest that the empirical use of a carbapenem-colistin combination should be evaluated in late-onset VAP following broad-spectrum antimicrobial exposure.