Strategies to reduce curative antibiotic therapy in intensive care units (adult and paediatric)

Emerging resistance to antibiotics shows no signs of decline. At the same time, few new antibacterials are being discovered. There is a worldwide recognition regarding the danger of this situation. The urgency of the situation and the conviction that practices should change led the Société de Réanimation de Langue Française (SRLF) and the Société Française d'Anesthésie et de Réanimation (SFAR) to set up a panel of experts from various disciplines. These experts met for the first time at the end of 2012 and have since met regularly to issue the following 67 recommendations, according to the rigorous GRADE methodology. Five fields were explored: i) the link between the resistance of bacteria and the use of antibiotics in intensive care; ii) which microbiological data and how to use them to reduce antibiotic consumption; iii) how should antibiotic therapy be chosen to limit consumption of antibiotics; iv) how can antibiotic administration be optimized; v) review and duration of antibiotic treatments. In each institution, the appropriation of these recommendations should arouse multidisciplinary discussions resulting in better knowledge of local epidemiology, rate of antibiotic use, and finally protocols for improving the stewardship of antibiotics. These efforts should contribute to limit the emergence of resistant bacteria.(AU)

Impact of imipenem and amikacin pharmacokinetic/pharmacodynamic parameters on microbiological outcome of Gram-negative bacilli ventilator-associated pneumonia.

OBJECTIVES: Despite recent advances, antibiotic therapy of ventilator-associated pneumonia (VAP) in ICU patients is still challenging. We assessed the impact of imipenem and amikacin pharmacokinetic and pharmacodynamic parameters on microbiological outcome in these patients. PATIENTS AND METHODS: Patients with Gram-negative bacilli (GNB) VAP were prospectively included. Blood samples for pharmacokinetic analysis were collected after empirical administration of a combination of imipenem three times daily and one single dose of amikacin. MICs were estimated for each GNB obtained from respiratory samples. Microbiological success was defined as a ≥10(3) cfu/mL decrease in bacterial count in quantitative cultures between baseline and the third day of treatment. RESULTS: Thirty-nine patients [median (min-max) age = 60 years (28-84) and median SAPS2 at inclusion = 40 (19-73)] were included. Median MICs of imipenem and amikacin were 0.25 mg/L (0.094-16) and 2 mg/L (1-32), respectively. Median times over MIC and over 5× MIC for imipenem were 100% (8-100) and 74% (3-100), respectively. The median C1/MIC ratio for amikacin was 23 (1-76); 34 patients (87%) achieved a C1/MIC ≥10. Microbiological success occurred in 29 patients (74%). No imipenem pharmacodynamic parameter was significantly associated with the microbiological success. For amikacin, C1/MIC was significantly higher in the microbiological success group: 26 (1-76) versus 11 (3-26) (P = 0.004). CONCLUSIONS: In ICU patients with VAP, classic imipenem pharmacodynamic targets are easily reached with usual dosing regimens. In this context, for amikacin, a higher C1/MIC ratio than previously described might be necessary.

Population pharmacokinetics of single-dose amikacin in critically ill patients with suspected ventilator-associated pneumonia.

AIMS: Modifications of antimicrobials' pharmacokinetic parameters have been reported in critically ill patients, resulting in a risk of treatment failure. We characterized amikacin pharmacokinetic variability in critically ill patients with ventilator-associated pneumonia (VAP) and evaluated several dosing regimens. METHODS: We conducted a prospective multicenter study in critically ill patients with presumptive diagnosis of Gram-negative bacilli (GNB) VAP. Patients empirically received imipenem and a single-dose of amikacin, which was administered as a 30-min infusion (20 mg/kg). Concentrations were measured 0.5, 1, 8, 16, and 24 h after beginning of infusion. Pharmacokinetic parameters were estimated using a population approach. Main pharmacodynamic target was a ratio ≥ 10 between the concentration achieved 1 h after beginning of infusion (C 1h) and the minimal inhibitory concentration of the liable bacteria (MIC). We simulated individual C 1h for several dosing regimens by Monte Carlo method and computed C 1h/MIC ratios for MICs from 0.5 to 64 mg/L. RESULTS: Sixty patients (47 males), median (range) age, and body weight, 61.5 years (28-84) and 78 kg (45-126), respectively, were included. Amikacin median C 1h was 45 mg/L (22-87). Mean value (between-patients variability) for CL, V1, Q, and V2 were 4.3 L/h (31 %), 15.9 L (22 %), 12.1 L/h (27 %), and 21.4 L (47 %), respectively. CL increased with CrCL (p<0.001) and V1 with body weight (p<0.001) and PaO2/FIO2 ratio (p<0.001). With a 25 mg/kg regimen, the pharmacodynamic target was achieved in 20 and 96 % for a MICs of 8 and 4 mg/L, respectively. CONCLUSION: Amikacin clearance was decreased and its volume of distribution was increased as previously reported. A ≥ 25 mg/kg single-dose is needed for empirical treatment of GNB-VAP.

[Ocular syphilis. A report of two patients]. / Syphilis oculaire : à propos de deux cas.

INTRODUCTION: Whereas syphilis is a classical cause of uveitis, it is still often under-recognized. Treatment recommendations are not based on specific clinical studies. CASE REPORTS: We report two patients with syphilitic uveitis diagnosed and treated at the University Hospital of Angers. Ocular involvement was inaugural in both patients. Each had a specific treatment but none had a complete recovery of visual function. CONCLUSION: Syphilis must be discussed in all patients diagnosed with uveitis or papillitis. Although not evidence-based, prompt therapy may lead to functional recovery.

[Phacoemulsification: advantages of a consultation the day after surgery?]. / Phacoémulsification : intérêt de la visite du lendemain ?

INTRODUCTION: Cataract surgery is the most frequent surgery in France. The D1 consultation limits the extension of ambulatory care to patients who can return on their own the day after sugery. We assessed the usefulness of this systematic D1 consultation in terms of therapeutic modifications. MATERIAL AND MéTHODE: Retrospective study of patients who underwent cataract surgery in a teaching hospital from february to july 2006. The major parameter was the modification of postsurgical treatment after the D1 consultation. RESULTS: Of the 380 operated eyes studied, the patients included 145 men and 235 women, the mean age was 73.8 years (range, 43-92), 86% underwent conventional hospitalization, 70% had been operated by a senior surgeon, and 66% had no suture. At the D1 visit, 11 modifications (2.9%) were recorded: one case of athalamia, one Seidel-positive test, four cases of high IOP (>30mmHg), and five severe inflammations of the anterior segment. All the treatment changes were reported in the group of hospitalized patients, none were reported in the ambulatory patients. Of the 380 eyes studied, only one required sutures at D1, the other treatment changes were minor. CONCLUSIONS: The low output of the D1 visit raises the problem of its relevance in terms of public health. In most of the English-speaking and Scandinavian countries, patients have only one postoperative visit at 1 month. Patients could receive written and oral recommendations and a hotline number to contact the surgical team, which could allow the D1 visit to be discontinued for standard patients with uncomplicated surgery.

Abdominal compartment syndrome and intraabdominal sepsis: two of the same kind?

BACKGROUND: Abdominal compartment syndrome and intra-abdominal hypertension are frequently associated with peritonitis. The aim of this study is to establish the relationship between intra-abdominal hypertension and intra-abdominal sepsis especially in critically ill patients. METHODS: Relevant information was identified through a Medline search (1966-October 2006). The terms used were "intra-abdominal sepsis", "peritonitis", "abdominal compartment syndrome", "intra-abdominal hypertension" and "relaparotomy for sepsis". The search was limited to English- and French-language publications. RESULTS: Only a few clinical trials exist on this specific topic. Further investigations are required to define the incidence of intra-abdominal hypertension in intra-abdominal sepsis, and the prognostic impact of this setting and finally the potential specific treatment. Abdominal compartment syndrome is more likely linked to the abdominal surgery than to peritonitis itself. CONCLUSION: Intra-abdominal pressure monitoring can be valuable in critically ill patients with suspicion of persisting intra-abdominal sepsis after surgical peritonitis treatment.

[Granuloma annulare of the eyelid in a child: an atypical localization]. / Granulome annulaire des paupières: une localisation atypique.

BACKGROUND: Granuloma annulare is a common form of dermatosis in children and young adults. Lesions are typically found on the hands, the feet and the extensor surfaces of the limbs, and occasionally on the trunk. We report a case original in terms of its palpebral localization. CASE-REPORT: A 5 year-old girl consulted for papular lesions on the eyelids. The clinical examination revealed papules on the right lower eyelid measuring 8 mm, on the left lower eyelid measuring 5 mm and on the right upper eyelid measuring 3 mm. Laboratory tests including serum glucose, lipids and calcium as well as a complete blood count proved normal. Biopsy showed granulomatous lesions: a region of central necrosis surrounded by a palisade of inflammatory cells confirmed the diagnosis of granuloma annulare. The lesions disappeared in a few weeks without treatment. DISCUSSION: To our knowledge, 44 cases of granuloma annulare of the periorbital area have been reported, of which 19 concerned children. This presentation represents an atypical localization of granuloma annulare which must not be confused with many other palpebral disorders. Biopsy is necessary to confirm the diagnosis.

Abdominal compartment syndrome and intraabdominal sepsis: two of the same kind?

BACKGROUND: Abdominal compartment syndrome and intra-abdominal hypertension are frequently associated with peritonitis. The aim of this study is to establish the relationship between intra-abdominal hypertension and intra-abdominal sepsis especially in critically ill patients. METHODS: Relevant information was identified through a Medline search (1966-October 2006). The terms used were "intra-abdominal sepsis", "peritonitis", "abdominal compartment syndrome", "intra-abdominal hypertension" and "relaparotomy for sepsis". The search was limited to English- and French-language publications. RESULTS: Only a few clinical trials exist on this specific topic. Further investigations are required to define the incidence of intra-abdominal hypertension in intra-abdominal sepsis, and the prognostic impact of this setting and finally the potential specific treatment. Abdominal compartment syndrome is more likely linked to the abdominal surgery than to peritonitis itself. CONCLUSION: Intra-abdominal pressure monitoring can be valuable in critically ill patients with suspicion of persisting intra-abdominal sepsis after surgical peritonitis treatment.

Maintenance therapy with cotrimoxazole for toxoplasmic encephalitis in the era of highly active antiretroviral therapy.

To reduce the number of daily pills for improving adherence to antiretrovirals, 17 protease inhibitor-treated patients receiving toxoplasmic encephalitis (TE) standard maintenance therapy were instead given cotrimoxazole 960 mg twice daily. After a median follow-up of 31 months, one relapsed after three months, TE relapse incidence = 2.1 cases per 100 patient-years (95% confidence interval, 0.05-11.3). This strategy could be useful for patients awaiting immune reconstitution which allows the interruption of TE maintenance therapy.

Retinopathy, hematuria, and diabetic nephropathy.

We have retrospectively analyzed the incidence of diabetic nephropathy in 21 diabetic patients who underwent renal biopsy between 1985 and 1995 for microscopic hematuria and/or proteinuria >2.5 g/day without retinopathy. Diabetic nephropathy was observed in 13 of 21 patients (62%). 50% of our patients with diabetic nephropathy had hematuria, the incidence being higher in type I as compared with type II diabetic patients (30 vs. 20%). Diabetic nephropathy without retinopathy but with hematuria was noted in 5 of 13 patients, and diabetic nephropathy without retinopathy and hematuria was also noted in 5 of 13 patients. We suggest from our retrospective analysis that renal-retinal diabetic syndrome really exists.