Monotherapy in serious hospital-acquired infections: a clinical trial of ceftazidime versus imipenem/cilastatin

The clinical and bacteriological efficacy and safety of the antibiotics ceftazidime or imipenem/cilastatin in seriously ill patients with nosocomial infections were compared in a prospective, open, evaluator-blind, multicentre comparative trial. The study was performed in 26 European centres, the majority being intensive care units. Subjects were randomized to receive either ceftazidime 2 g bid or imipenem cilastatin 0·5 g qid given for at least five days after stratification for pneumonia, septicaemia or urinary tract infection (UTI). Three hundred and ninety-three patients with serious nosocomial infections (254 with pneumonia; 91 with septicaemia and 48 UTI were treated between February 1988 and January 1990 and their clinical and bacteriological response to antibiotic treatment assessed. There were no significant differences between ceftazidime and imipenem/cilastatin in clinical efficacy. The failure rates in evaluable patients were 22 and 26% in pneumonia, 23 and 19% in septicaemia and 0 and 5% respectively in those with UTI. Overall there was no significant difference between the two antibiotics for bacteriological response in the three infection strata. However, in patients with pneumonia ceftazidime was significantly more effective than imipenem/cilastatin in clearing patients of Pseudomonas spp.: 3/17 and 11/19 patients respectively had persistent growth of Pseudomonas spp. post-treatment (P = 0·004), and in one ceftazidime failure resistance emerged compared to six imipenem/cilastatin failures in which resistance emerged. Few drug-related adverse events were recorded in either treatment group. Monotherapy with either ceftazidime (2 g bid) or imipenem/cilastatin (0·5 g qid) is safe and effective and could be considered as an alternative to combination therapy for the treatment of serious hospital-acquired infection

Consistent biofilm formation by Streptococcus pyogenes emm 1 isolated from patients with necrotizing soft tissue infections

Objectives: Biofilm formation has been demonstrated in muscle and soft tissue samples from patients with necrotizing soft tissue infection (NSTI) caused by Streptococcus pyogenes, but the clinical importance of this observation is not clear. Although M-protein has been shown to be important for in vitro biofilm formation in S. pyogenes, the evidence for an association between emm type and biofilm forming capacity is conflicting. Here we characterize the biofilm forming capacity in a collection of S. pyogenes isolates causing NSTI, and relate this to emm type of the isolates and clinical characteristics of the patients. Methods: Bacterial isolates and clinical data were obtained from NSTI patients enrolled in a multicenter prospective observational study. Biofilm forming capacity was determined using a microtiter plate assay. Results: Among 57 cases, the three most frequently encountered emm types were emm1 (n = 22), emm3 (n = 13), and emm28 (n = 7). The distribution of biofilm forming capacity in emm1 was qualitatively (narrow-ranged normal distribution) and quantitatively (21/22 isolates in the intermediate range) different from other emm types (wide ranged, multimodal distribution with 5/35 isolates in the same range as emm1). There were no significant associations between biofilm forming capacity and clinical characteristics of the patients. Conclusions: The biofilm forming capacity of emm1 isolates was uniform and differed significantly from other emm types. The impact of biofilm formation in NSTI caused by S. pyogenes on clinical outcomes remains uncertain.publishedVersio

Antimicrobial Drug Resistance, Regulation, and Research1

Research models and regulatory measures could aid in developing antimicrobial drugs to address bacterial resistance

Preparation, structural characterisation and antibacterial properties of Ga-doped sol-gel phosphate-based glass

A sol-gel preparation of Ga-doped phosphate-based glass with potential application in antimicrobial devices has been developed. Samples of composition (CaO)(0.30)(Na2O)(0.20-x) (Ga2O3) (x) (P2O5)(0.50) where x = 0 and 0.03 were prepared, and the structure and properties of the gallium-doped sample compared with those of the sample containing no gallium. Analysis of the P-31 MAS NMR data demonstrated that addition of gallium to the sol-gel reaction increases the connectivity of the phosphate network at the expense of hydroxyl groups. This premise is supported by the results of the elemental analysis, which showed that the gallium-free sample contains significantly more hydrogen and by FTIR spectroscopy, which revealed a higher concentration of -OH groups in that sample. Ga K-edge extended X-ray absorption fine structure and X-ray absorption near-edge structure data revealed that the gallium ions are coordinated by six oxygen atoms. In agreement with the X-ray absorption data, the high-energy XRD results also suggest that the Ga3+ ions are octahedrally coordinated with respect to oxygen. Antimicrobial studies demonstrated that the sample containing Ga3+ ions had significant activity against Staphylococcus aureus compared to the control

Accommodative lens refilling in rhesus monkeys

PURPOSE. Accommodation can be restored to presbyopic human eyes by refilling the capsular bag with a soft polymer. This study was conducted to test whether accommodation, measurable as changes in optical refraction, can be restored with a newly developed refilling polymer in a rhesus monkey model. A specific intra-and postoperative treatment protocol was used to minimize postoperative inflammation and to delay capsular opacification. METHODS. Nine adolescent rhesus monkeys underwent refilling of the lens capsular bag with a polymer. In the first four monkeys (group A) the surgical procedure was followed by two weekly subconjunctival injections of corticosteroids. In a second group of five monkeys (group B) a treatment intended to delay the development of capsular opacification was applied during the surgery, and, in the postoperative period, eye drops and two subconjunctival injections of corticosteroids were applied. Accommodation was stimulated with carbachol iontophoresis or pilocarpine and was measured with a Hartinger refractometer at regular times during a follow-up period of 37 weeks in five monkeys. In one monkey, lens thickness changes were measured with A-scan ultrasound. RESULTS. In group A, refraction measurement was possible in one monkey. In the three other animals in group A, postoperative inflammation and capsular opacification prevented refraction measurements. In group B, the maximum accommodative amplitude of the surgically treated eyes was 6.3 D. In three monkeys the accommodative amplitude decreased to almost 0 D after 37 weeks. In the two other monkeys, the accommodative amplitude remained stable at +/- 4 D during the follow-up period. In group B, capsular opacification developed in the postoperative period, but refraction measurements could still be performed during the whole follow-up period of 37 weeks. CONCLUSIONS. A certain level of accommodation can be restored after lens refilling in adolescent rhesus monkeys. During the follow-up period refraction measurements were possible in all five monkeys that underwent the treatment designed to prevent inflammation and capsular opacification