Combined meropenem and linezolid as a systemic treatment for postoperative endophthalmitis

PURPOSE The aim of this study was to evaluate the antibiotic treatment of postoperative endophthalmitis with combined systemic meropenem and linezolid. METHODS A retrospective analysis of endophthalmitis treated with systemic meropenem and linezolid compared to conventional systemic antibiotics by evaluation of outcome and adverse effects was carried out. RESULTS 26 patients with unilateral postoperative endophthalmitis with a systemic combination regimen of meropenem (2 g TID, mean duration of treatment 5.5 days) and linezolid (600 mg BID, mean duration of treatment 8.9 days) (group 1, mean follow-up time 140 days) were included in this study and compared to 45 postoperative endophthalmitis patients treated with conventional systemic antibiotics (group 2; mean follow-up time 320 days). In group 1, 69.2 % of eyes additionally received intravitreal amikacin and vancomycin (vs. 24.4 % in group 2; p < 0.001), in 92.3 % pars plana vitrectomy was performed (vs. 68.9 % in group 2, p = 0.047). Mean best corrected visual acuity improved from a baseline of 1.76 logMar for group 1 and 1.83 logMar for group 2 to 0.91 logMar (p = 0.0001) and 0.90 logMar (p < 0.0001), respectively, at the end of the follow-up, revealing no significant differences between the two groups at any time point (p > 0.05). Ocular complications were observed in 34.6 % of eyes in group 1 (vs. 37.8 % in group 2; p > 0.05). Adverse drug effects occurred significantly more frequently in group 1 (26.9 % vs. 4.4 % p = 0.02). CONCLUSION In spite of the reported better penetration through the blood-ocular barrier and the broader antibacterial spectrum of meropenem and linezolid, no benefit in outcome was found in the present study. In contrast, adverse effects and costs of the combination regimen were significantly higher.

Efficacy and safety of intravenous meropenem and tobramycin versus ceftazidime and tobramycin in cystic fibrosis

BACKGROUND: Cystic fibrosis (CF) is characterized by chronic bacterial broncho-pulmonary infection. Although intravenous (IV) antibiotic therapy is regarded as standard treatment in CF, only few randomised trials comparing different antibiotic compounds exist. METHODS: We report on a prospective multicenter interventional trial of IV meropenem (120 mg/kg/day) or IV ceftazidime (200-400 mg/kg/day), each administered together with IV tobramycin (9-12 mg/kg/day). Outcome measures were changes in lung function, microbiological sputum burden and blood inflammatory marker. Liver and renal function values were measured to assess safety. RESULTS: One hundred eighteen patients (59/59) were included into the study with the following indications: first infection of P. aeruginosa (n=6), acute pulmonary exacerbation (n=34) and suppression therapy of chronic P. aeruginosa colonization (n=78). Both treatments improved lung function measures, bacterial sputum burden and CRP levels with no differences between treatment groups observed. A significant higher elevation for alkaline phosphatase (p<0.0001) was observed for patients in the meropenem/tobramycin group. CONCLUSIONS: IV antibiotic therapy in CF patients with meropenem/tobramycin is as effective as with ceftazidime/tobramycin regarding lung function, microbiological sputum burden and systemic inflammatory status. Hepato-biliary function should be monitored carefully during IV treatment, possibly important in CF patients with pre-existing liver disease.

Fluoroquinolones in the Treatment of Meningitis

The continuous increase of resistant pathogens causing meningitis has limited the efficacy of standard therapeutic regimens. Due to their excellent activity in vitro and their good penetration into the cerebrospinal fluid (CSF), fluoroquinolones appear promising for the treatment of meningitis caused by gram-negative microorganisms, ie, Neisseria meningitidis and nosocomial gram-negative bacilli. The newer fluoroquinolones (moxifloxacin, gemifloxacin, gatifloxacin, and garenoxacin) have excellent activity against gram-positive microorganisms. Studies in animal models and limited clinical data indicate that they may play a future role in the treatment of pneumococcal meningitis. Analysis of pharmacodynamic parameters suggests that CSF concentrations that produce a C(peak)/minimal bactericidal concentration (MBC) ratio of at least 5 and concentrations above the MBC during the entire dosing interval are a prerequisite for maximal bactericidal activity in meningitis. Of interest, newer fluoroquinolones act synergistically with vancomycin and beta-lactam antibiotics (ceftriaxone, cefotaxime, meropenem) against penicillin-resistant pneumococci in experimental rabbit meningitis, potentially providing a new therapeutic strategy. Clinical trials are needed to further explore the usefulness of quinolones as single agents or in combination with other drugs in the therapy of pneumococcal meningitis.