Fosfomycin: use beyond urinary tract and gastrointestinal infections.

The shortage of new antimicrobial agents has made the scientific community reconsider the potential value of old antibiotics. A search of the literature was performed to compile relevant evidence regarding the effectiveness and safety of fosfomycin for the treatment of patients with gram-positive and/or gram-negative bacterial infections (excluding urinary tract infection and gastrointestinal infection). Of 1311 potentially relevant studies, 62 studies were reviewed in detail. Of 1604 patients with various gram-positive and gram-negative infections of various body sites (including pneumonia and other respiratory infections; osteomyelitis; meningitis; ear, nose, and throat infections; surgical infections; obstetric and gynecological infections; arthritis; septicemia; peritonitis; cervical lymphadenitis; eye infections; diabetic foot infections; and typhoid fever) being treated with fosfomycin alone or in combination with other antibiotics, cure was achieved in 1302 (81.1%) of the patients, and improvement was noted in 47 (2.9%). In comparative perioperative prophylaxis trials that included a total of 1212 patients (mainly patients undergoing colorectal surgery), the fosfomycin-metronidazole combination led to results that were similar to those achieved with the combination of other antibiotics (doxycycline, ampicillin, or cephalothin) and metronidazole. In an era in which there is a shortage of new antibiotics, fosfomycin might be considered to be an alternative treatment agent for infections caused by gram-positive and gram-negative bacteria, in addition to its traditional use in treating uncomplicated urinary tract and gastrointestinal infections. Further research on the in vitro antimicrobial activity of fosfomycin, especially against multidrug-resistant pathogens (such as extended-spectrum beta-lactamase-producing and/or metallo-beta-lactamase-producing enterobacteriaceae and Pseudomonas aeruginosa, and on the effectiveness and safety of the drug in the treatment of patients with such infections may be warranted.

Comparison of antibiotics with placebo for treatment of acute sinusitis: a meta-analysis of randomised controlled trials.

We did a meta-analysis of randomised controlled trials (RCTs) to assess the therapeutic role of antibiotics for acute sinusitis compared with placebo. Eligible studies were retrieved from PubMed and Scopus. 17 double-blind RCTs were included (three involving children). Acute sinusitis was diagnosed with clinical criteria in nine RCTs, imaging studies in six RCTs, and microbiological or laboratory methods in two RCTs. Amoxicillin was used in ten of 23 antibiotic treatment groups. To account for potential statistical heterogeneity between studies, a random-effects model was used for all analyses. Compared with placebo, antibiotics were associated with a higher rate of cure or improvement (2648 patients, odds ratio [OR] 1.64 [95% CI 1.35-2.00], data from 16 RCTs), or cure alone (1813 patients, OR 1.82 [1.34-2.46], 12 RCTs), but also with more adverse events (1963 patients, OR 1.87 [1.21-2.90], 12 RCTs). The rate of symptom resolution was faster with antibiotics in most RCTs. Disease complications, disease recurrence, and study withdrawals because of adverse events did not differ between compared treatments. In conclusion, use of antibiotics for acute sinusitis confers a small therapeutic benefit over placebo with a corresponding rise in the risk for adverse events. We suggest that antibiotics should be reserved for carefully selected patients with a higher probability for bacterial disease.

Matching criteria in case-control studies in the field of antimicrobial resistance.

OBJECTIVE: We evaluated the available evidence from case-control studies in the field of antimicrobial resistance to identify the degree that matching was performed and the criteria used to do so. METHODS: We performed a systematic search of the PubMed database (articles archived by 08/2006) to identify relevant studies. Studies that used the individual matching technique were further analyzed. RESULTS: 115 case-control studies with a focus on antimicrobial resistance were identified: 28 regarding Acinetobacter baumannii, 25 regarding Pseudomonas aeruginosa, and 62 for other bacteria. Individual matching was performed in 32 (27.8%) out of the 115 studies. Age was the most frequently used matching criterion in 22 of 32 (69%) evaluated matched case-control studies, while sex was used in 11 (34%), presence of underlying illness in 8 (25%), site of infection in 5 (16%), and area of residence in 4 studies (12.5%). Other criteria were used in less than 10% of the studies. Analysis of data for matched pairs was performed in 18 of 32 (56.3%) studies that used a matched case-control design. DISCUSSION: The available evidence from the analyzed data from case-control studies in the field of antimicrobial resistance shows that individual matching is employed only in a proportion of such studies and only for a few characteristics, when it was used. Also, analysis for matched pairs was not used by almost a half of the relevant studies.

Fluoroquinolones compared with beta-lactam antibiotics for the treatment of acute bacterial sinusitis: a meta-analysis of randomized controlled trials.

BACKGROUND: The presumed superiority of newer fluoroquinolones for the treatment of acute bacterial sinusitis is based on laboratory data but has not yet been established on clinical grounds. METHODS: We performed a meta-analysis of randomized controlled trials comparing the effectiveness and safety of fluoroquinolones and beta-lactams in acute bacterial sinusitis. RESULTS: We identified 8 randomized controlled trials investigating the newer "respiratory" fluoroquinolones moxifloxacin, levofloxacin and gatifloxacin. In the primary effectiveness analysis involving 2133 intention-to-treat patients from 5 randomized controlled trials, the extent of clinical cure and improvement did not differ between fluoroquinolones and beta-lactams (odds ratio [OR] 1.09, 95% confidence interval [CI] 0.85-1.39) at the test-of-cure assessment, which varied from 10 to 31 days after the start of treatment. Fluoroquinolones were associated with an increased chance of clinical success among the clinically evaluable patients in all of the randomized controlled trials (OR 1.29, 95% CI 1.03-1.63) and in 4 blinded randomized controlled trials (OR 1.45, 95% CI 1.05-2.00). There was no statistically significant difference between fluoroquinolones and amoxicillin-clavulanate (OR 1.24, 95% CI 0.93-1.65). Eradication or presumed eradication of the pathogens isolated before treatment was more likely with fluoroquinolone treatment than with beta-lactam treatment (OR 2.11, 95% CI 1.09-4.08). In the primary safety analysis, adverse events did not differ between treatments (OR 1.17, 95% CI 0.86-1.59). However, more adverse events occurred with fluoroquinolone use than with beta-lactam use in 2 blinded randomized controlled trials. The associations described here were generally consistent when we included 3 additional studies involving other fluoroquinolones (ciprofloxacin and sparfloxacin) in the analysis. INTERPRETATION: In the treatment of acute bacterial sinusitis, newer fluoroquinolones conferred no benefit over beta-lactam antibiotics. The use of fluoroquinolones as first-line therapy cannot be endorsed.

Daptomycin for treatment of patients with bone and joint infections: a systematic review of the clinical evidence.

The treatment of bone and joint infections, mainly caused by Gram-positive pathogens, can be difficult and quite challenging since it frequently involves prolonged administration of antibiotics as well as appropriate surgical procedures. First-line drugs have failed in some cases to cure the underlying infection. We performed a systematic review of the available evidence to clarify further the effectiveness and safety of daptomycin in the treatment of bone and joint infections. Cure of infection was achieved in 43/53 cases (81.1%). The results of the reviewed articles are promising with regard to the effectiveness and safety profile of this new antibiotic for bone and joint infections that are not responsive to other traditionally used antimicrobial agents. Although these reports are encouraging, the relatively frequent emergence of antimicrobial resistance associated with prolonged administration of daptomycin should be considered seriously.

Treatment of viral conjunctivitis with antiviral drugs.

Viral conjunctivitis is one of the most common disorders observed in ophthalmic emergency departments, yet no established treatment exists. Lately, antiviral medications have been introduced into clinical practice; however, a systematic review focusing on their use and effectiveness in the treatment of viral conjunctivitis has not been previously reported. We systemically reviewed the literature to identify studies where antiviral drugs were used to treat viral conjunctivitis. Currently, aciclovir, trifluridine and valaciclovir are commonly used as antiviral agents to treat herpesvirus infections. Cidofovir has been used successfully to treat some cases of adenoviral conjunctivitis, although toxicity has also been reported. The use of other medications, such as idoxuridine, has been minimized in clinical practice due to their high toxicity. Interestingly, most of the antiviral drugs developed are used to treat herpesvirus infections, while less progress has been made in the field of adenoviral infections. For other viral causes of conjunctivitis, no effective remedy is currently available, and treatment focuses on the relief of symptoms. Caution should be exercised when coadministering other pharmacological agents, such as corticosteroids, because of emerging adverse effects.

Informed consent: how much and what do patients understand?

OBJECTIVE: We sought to evaluate the degree of patients' understanding of several aspects of the informed consent process for surgery and clinical research. METHODS: We conducted a systematic search of PubMed (1961-2006) to identify relevant articles. RESULTS: We retrieved 23 and 30 eligible for inclusion articles regarding informed consent for surgery and clinical research, respectively. Regarding surgery, adequate overall understanding of the information provided and of the risks associated with surgery was shown in 6 of 21 (29%) and 5 of 14 (36%) studies providing relevant data, respectively. Regarding clinical research, adequate understanding of the aim of the study, the process of randomization, voluntarism, withdrawal, and the risks and the benefits of treatment was shown in 14 of 26 (54%), 4 of 8 (50%), 7 of 15 (47%), 7 of 16 (44%), 8 of 16 (50%), and 4 of 7 (57%) of studies providing relevant data, respectively. Satisfaction by the amount of the given information was shown in 7 of 12 (58%) studies involving surgery and 12 of 15 (80%) studies involving clinical research. CONCLUSIONS: Further attention should be drawn on enhancing patients' understanding regarding several components of the informed consent process for surgery and clinical research.

Candida albicans versus non-albicans bloodstream infection in patients in a tertiary hospital: an analysis of microbiological data.

Considerable changes in the relative frequency of systemic infections due to various Candida species as well as their in vitro susceptibility patterns have been noted in several parts of the world. We performed an analysis of microbiological data of patients with candidaemia at the University general (tertiary) hospital of Heraklion, Greece. During the study period (March 2001 to July 2006) 140 patients had candidaemia. Among them, 64/140 (46%) had candidaemia due to C. albicans and 76/140 (54%) due to non-albicans species (19/76, 25%, C. glabrata; 30/76, 40%, C. tropicalis; 20/76, 26%, C. parapsilosis; 2/76, 3%, C. lusitaniae; 3/76, 4%, C. krusei; and 2/76, 3%, C. guilliermondii). 75 isolates were tested for in vitro susceptibility to antifungal agents with E-test. No isolate was found to be resistant to amphotericin. From 34 C. albicans isolates, 5 (15%) were not susceptible to itraconazole, and 1 (3%) to fluconazole. The C. guilliermondii and the C. lusitaniae isolates were not susceptible to itraconazole. All 11 C. glabrata isolates were not susceptible to ketoconazole and itraconazole, with only 5 (45%) to fluconazole. In line with results of other relevant studies, we documented that a considerable proportion of Candida bloodstream infections were due to non-albicans Candida species.

Daptomycin for endocarditis and/or bacteraemia: a systematic review of the experimental and clinical evidence.

BACKGROUND: Endocarditis and bacteraemia are devastating infections with high mortality. Gram-positive cocci are the most commonly isolated pathogens. In an era of multidrug-resistant pathogens, the evaluation of new treatment options is important. Daptomycin is a cyclic lipopeptide that is active against most of these pathogens. Furthermore, it is a bactericidal antibiotic, a factor that is frequently considered in the choice of treatment of patients with bacteraemia and endocarditis. METHODS: We performed a systematic review of the evidence for the effectiveness of daptomycin in the treatment of patients and animals with endocarditis and/or bacteraemia. We searched PubMed and Scopus databases for relevant studies. Case reports, case series, controlled trials, randomized controlled trials and comparative studies using experimental animal models were included. RESULTS: The most reliable information comes from the single multicentre randomized controlled trial conducted on this issue, which showed that daptomycin is a promising antibiotic for the treatment of patients with Staphylococcus aureus bacteraemia and endocarditis. The experimental models indicate that the combination of daptomycin with rifampicin or gentamicin can improve outcomes further. Finally, in several of the published relevant case reports daptomycin was administered in patients with haematological malignancies. CONCLUSIONS: Daptomycin is a promising antibiotic that has been already approved for the treatment of patients with right-sided endocarditis and bacteraemia. However, the available clinical evidence is limited and further evaluation of the antibiotic is warranted. The commonly reported de novo development of resistance is a major concern that may limit its use. More controlled trials are needed, especially for patients infected with multidrug-resistant Gram-positive cocci, comparing daptomycin with other available treatment options, including glycopeptides and oxazolidinones.

Risk factors for mortality in patients with emphysematous pyelonephritis: a meta-analysis.

PURPOSE: Emphysematous pyelonephritis, an infection most commonly seen in cases of diabetes mellitus, is associated with considerable case fatality. We identified the factors associated with mortality in patients with emphysematous pyelonephritis and estimated the magnitude of the associations. MATERIALS AND METHODS: PubMed was searched to identify studies reporting on risk factors of mortality in patients with emphysematous pyelonephritis. A meta-analysis of the eligible studies was performed. RESULTS: Seven study cohorts, representing 175 patients with emphysematous pyelonephritis, were included in the meta-analysis. The overall mortality rate was 25%, ranging from 11% to 42%. Conservative treatment alone (OR 2.85, 95% CI 1.19-6.81), bilateral emphysematous pyelonephritis (OR 5.36, 95% CI 1.41-20.33), type I emphysematous pyelonephritis (OR 2.53, 95% CI 1.13-5.65) and thrombocytopenia (OR 22.68, 95% CI 4.4-116.32) were associated with increased mortality. Systolic blood pressure less than 90 mm Hg, serum creatinine greater than 2.5 mg/dl and disturbance of consciousness were also found to be associated with increased mortality. However, this finding was based on limited data. On the other hand, there was no association between mortality and diabetes mellitus (OR 0.32, 95% CI 0.05-1.99) in patients with emphysematous pyelonephritis. CONCLUSIONS: The accumulated and analyzed evidence suggests that conservative treatment, type I emphysematous pyelonephritis, bilateral emphysematous pyelonephritis and thrombocytopenia seem to be significant risk factors for mortality in patients with emphysematous pyelonephritis. These data may be taken into consideration when treating patients with this devastating infection.