Fosfomycin.

The treatment of bacterial infections suffers from two major problems: spread of multidrug-resistant (MDR) or extensively drug-resistant (XDR) pathogens and lack of development of new antibiotics active against such MDR and XDR bacteria. As a result, physicians have turned to older antibiotics, such as polymyxins, tetracyclines, and aminoglycosides. Lately, due to development of resistance to these agents, fosfomycin has gained attention, as it has remained active against both Gram-positive and Gram-negative MDR and XDR bacteria. New data of higher quality have become available, and several issues were clarified further. In this review, we summarize the available fosfomycin data regarding pharmacokinetic and pharmacodynamic properties, the in vitro activity against susceptible and antibiotic-resistant bacteria, mechanisms of resistance and development of resistance during treatment, synergy and antagonism with other antibiotics, clinical effectiveness, and adverse events. Issues that need to be studied further are also discussed.

Susceptibility patterns of uropathogens identified in hospitalised children with community-acquired urinary tract infections in Thrace, Greece.

Urinary tract infections (UTIs) are common infections associated with considerable morbidity and mortality, particularly in paediatric patients. The alarmingly increasing antimicrobial resistance of contemporary uropathogens in children necessitates the re-evaluation of antibiotic treatment. We evaluated uropathogens isolated from children hospitalised due to a community-acquired UTI over a 5.5-year period in a university hospital of Northern Greece and their antibiotic susceptibility patterns. The antibiotic susceptibility of uropathogens was compared by patient sex and age. Bacterial identification and antibiotic susceptibility testing were performed by the automated VITEK® 2 system and the Kirby-Bauer method. Overall, 221 urinary isolates were identified from 218 children with a documented UTI, including 170 (76.9%) Escherichia coli, 17 (7.7%) Proteus spp., 15 (6.8%) Klebsiella spp., 9 (4.1%) Pseudomonas aeruginosa, 4 (1.8%) Enterococcus faecalis, 2 (0.9%) Enterobacter spp., 2 (0.9%) Morganella morganii and 2 (0.9%) Serratia fonticola. Comparing antibiotic susceptibilities of E. coli isolates by age [≤2 years vs. >2 years] and sex did not show any significant differences. Only 80 (49.1%) of the 163 tested E. coli isolates were found to be susceptible to ampicillin, whereas susceptibility to amoxicillin/clavulanic acid (AMC), ampicillin/sulbactam, trimethoprim/sulfamethoxazole and nitrofurantoin was 78.3%, 78.9%, 75.3% and 96.9%, respectively. Parenteral second- and third-generation cephalosporins, aminoglycosides and carbapenems were highly active against almost all uropathogens. We conclude that ampicillin should not be used for empirical therapy of paediatric community-acquired UTIs in our region. AMC and oral second-generation cephalosporins cover ca. 80% of uropathogenic E. coli, whilst nitrofurantoin is an appealing option for UTI chemoprophylaxis.

Hepatitis B vaccine alone or with hepatitis B immunoglobulin in neonates of HBsAg+/HBeAg- mothers: a systematic review and meta-analysis.

OBJECTIVES: The cost-effectiveness of augmenting immunization against hepatitis B infection with hepatitis B immunoglobulin (HBIG) remains controversial, particularly for the subpopulation of babies of HBsAg+/HBeAg- mothers that are considered as low-infective. We aimed to evaluate the effectiveness of vaccine alone compared with vaccine plus HBIG for the immunization of babies of HBsAg+/HBeAg- mothers. METHODS: We searched PubMed, Scopus and Cochrane Central Register of Controlled Trials databases to identify studies comparing the effectiveness of combined immunization (vaccine plus HBIG) with vaccine alone in neonates of HBsAg+/HBeAg- mothers. A systematic review and meta-analysis of eligible studies was performed. RESULTS: A total of nine eligible studies were identified (four randomized controlled trials). No difference was found regarding the primary outcome of our meta-analysis, namely occurrence of hepatitis B infection, between neonates who received vaccine only, compared with those who received both vaccine and HBIG (four studies, 3426 patients, OR=0.82, 95% CI=0.41-1.64). This finding was consistent with regards to seroprotection rate (four studies, 1323 patients, OR=1.24, 95% CI=0.97-1.58). Safety data were not reported in the included studies. CONCLUSIONS: The available limited published evidence suggests that vaccine alone seems to be equally effective to the combination of HBIG and hepatitis B vaccine for neonates of HBsAg+/HBeAg- mothers in preventing infection. Further studies are needed in order to clarify the potential benefit of combined immunization to this specific subgroup of patients.

Use of real-time polymerase chain reaction for the diagnosis of Pneumocystis pneumonia in immunocompromised patients: a meta-analysis.

BACKGROUND: The diagnosis of Pneumocystis pneumonia (PCP) in immunocompromised patients is still challenging today due to the absence of an in vitro culture system and the low diagnostic accuracy of microscopic examinations. Herein, we performed a meta-analysis to evaluate the accuracy of real-time polymerase chain reaction (PCR) in the diagnosis of PCP. METHODS: We searched Web of Knowledge and Medline from 1990 to May 2010 for studies reporting diagnostic accuracy data regarding the use of real-time PCR in the diagnosis of PCP in immunocompromised patients. RESULTS: Ten individual studies were included. Overall, the sensitivity of real-time PCR was 97% (95%CI: 93% - 99%); the specificity was 94% (95%CI: 90% - 96%). The area under the HSROC curve (95%CI) for real-time PCR was 0.99 (0.97 - 0.99). In a subgroup analysis regarding studies involving HIV patients among the study population, the sensitivity and specificity were 97% (95%CI: 93% - 99%) and 93% (95%CI: 89% - 96%), respectively. Regarding studies using Bronchoalveolar lavage (BAL) samples only: sensitivity = 98% (95%CI: 94% - 99%); specificity = 93% (95%CI: 89% - 96%), respectively. Regarding studies using microscopy as a reference standard: sensitivity = 97% (95%CI: 92% - 99%); specificity = 93% (95%CI: 88% - 96%). However, high between-study statistical heterogeneity was observed in all analyses. CONCLUSIONS: Real-time PCR has a good diagnostic accuracy and may provide a useful adjunctive tool for the diagnosis of PCP in immunocompromised patients. Further studies are needed in order to identify any differences in the diagnostic performance of real-time PCR in HIV and non-HIV immunocompromised patients.

Deep venous thrombosis in children with musculoskeletal infections: the clinical evidence.

BACKGROUND: Clinical manifestations of deep venous thrombosis (DVT) tend to overlap with those of deep-seated musculoskeletal infections (MSIs). Consequently, the incidence of DVT as a complication of MSI may be underestimated. The objective of this study was to evaluate the incidence, clinical features, and outcomes of MSI-related DVT in children. METHODS: We systematically reviewed relevant studies retrieved from PubMed and Scopus databases. RESULTS: Overall, 93 children with MSIs who developed DVT were identified from 28 retrospective studies. The majority were boys. Osteomyelitis was the most frequent MSI (69/74, 93%). Staphylococcus aureus was the predominant pathogen (83/93, 89%); 61% of these isolates were methicillin-resistant S. aureus (MRSA). Pulmonary involvement, presumably due to septic emboli, was observed in 65% of the included children. Four children died due to multiple organ failure and two due to respiratory distress. In two of the three studies providing comparative data, MRSA infections were observed significantly more frequently in children who developed DVT compared to those who did not. Yet, the respective differences observed for methicillin-susceptible S. aureus (MSSA) infections were non-significant in these three studies. CONCLUSIONS: Despite the inclusion of many case reports and the retrospective design of the evaluated studies, our findings suggest that boys seem to be more frequently affected by MSIs complicated by DVT. Moreover, MRSA seems to be more frequently associated with DVT compared to MSSA. Pulmonary involvement appears to be a frequent complication. Prospective studies are needed in order to further clarify this issue.

Immediate hematological toxicity of linezolid in healthy volunteers with different body weight: a phase I clinical trial.

Linezolid is an important therapeutic option for infections from multi-drug resistant Gram-positive pathogens. However, prolonged linezolid treatment (>14 days) is considered to increase the risk of hematological adverse events. We aimed to evaluate the hematological safety profile of an i.v. single dose of linezolid in healthy volunteers of different body weight. We conducted a phase I clinical trial involving 20 healthy male Chinese volunteers that received an i.v. single dose of linezolid (600 mg). The study participants were assigned to two groups: low-weight (LW) group: 50 kg

Current diagnosis and management of infectious mononucleosis.

PURPOSE OF REVIEW: Infectious mononucleosis is a common, usually self-limited disease. However, infectious mononucleosis may present with severe manifestations. Complications may also occur. Consequently, diagnostic and treatment issues regarding infectious mononucleosis are of major importance. RECENT FINDINGS: In this review, we focus on the evaluation of articles providing diagnosis and treatment data for infectious mononucleosis, published during the past 2 years. Twelve studies, deriving from extended search in PubMed, were included. Nine studies provided diagnosis data. The evaluated diagnostic methods were real-time PCR (RT-PCR), IgM/IgG antibodies measured with different assays [measurement of Epstein-Barr virus viral load (EBV-VL) in peripheral blood, neutrophil/lymphocyte/monocyte counts, C-reactive protein values, and monospot test]. The sensitivities reported for RT-PCR were high. The available treatment data were scarce (three studies). Two of them suggested that antivirals (mainly acyclovir and valacyclovir) may have a role in the treatment of infectious mononucleosis with complications, whereas the remaining study presented novel potential therapeutic patents including 5-substituted uracyle, azacytosine derivatives, and peptides inhibiting EBV-mediated membrane fusion. SUMMARY: RT-PCR and measurement of EBV-VL may provide useful tools for the early diagnosis of infectious mononucleosis in cases with inconclusive serological results. Antiviral agents may provide a useful treatment option in patients with severe infectious mononucleosis.

Sutures versus staples for the management of surgical wounds: a meta-analysis of randomized controlled trials.

Surgical sutures are conventionally used in skin closure of surgical wounds. Alternative wound closure techniques include staples and adhesive strips. We aimed to evaluate sutures versus staples as methods of surgical wound closure by performing a meta-analysis. We searched PubMed, Scopus, and Cochrane Central Register of Controlled Trials for randomized controlled trials that compared sutures with staples for surgical wound closure. Trials referring to orthopedic operations were excluded. Twenty studies (involving a total of 2111 patients) were included. Five studies referred to obstetrics/gynecological operations, seven to general surgery, four to emergency care treatment, three to head/neck operations, and one to vascular surgery. Regarding the time needed for wound closure, staples were superior to sutures; the mean difference observed between the sutures and staples groups was 5.56 minutes per wound (95% confidence intervals [CI], 0.05 to 11.07). Wound infections were significantly fewer in the staples group compared with the sutures group(s) (12 studies, 1529 patients; odds ratio, 2.06; 95% CI, 1.20 to 3.51). In five studies, the use of staples was associated with significantly more pain compared with sutures. The majority of studies with available relevant data reported nonsignificant differences regarding the cosmetic result and patient's satisfaction. Our findings suggest that staples are associated with fewer wound infections compared with sutures in the evaluated types of surgery. However, in a rather limited number of studies, the use of staples was associated with more pain. Further studies incorporating more objective methods for assessment cosmetic and patient satisfaction are required to clarify this issue.

Trimethoprim/sulfametrole: evaluation of the available clinical and pharmacokinetic/pharmacodynamic evidence.

Emergence of resistance to widely used trimethoprim/sulfamethoxazole (TMP/SMX) as well as common adverse events in human immunodeficiency virus (HIV)-infected patients casts interest on combinations of TMP with other sulfonamides. Sulfametrole (SMT) combined with TMP could provide a choice for difficult-to-treat infections, particularly when administered intravenously. The objective of this review was to evaluate the available clinical and pharmacokinetic/pharmacodynamic (PK/PD) evidence regarding TMP/SMT, particularly in comparison with TMP/SMX. We reviewed the available evidence retrieved from searches in PubMed/Scopus/Google Scholar and by bibliography hand-searching. In total, 46 eligible studies (most published before 1997) were identified, 7 regarding intravenous (i.v.) TMP/SMT, 24 regarding oral TMP/SMT and 15 providing comparative data for TMP/SMT versus TMP/SMX. The antimicrobial activity of TMP/SMT was similar to TMP/SMX for Gram-positive isolates. A greater percentage of Escherichia coli and Proteus spp. isolates were susceptible to TMP/SMT compared with TMP/SMX. PK/PD data suggest a dosage adjustment of i.v. TMP/SMT in patients with seriously impaired renal function. Four randomised controlled trials and 16 non-comparative studies reported good effectiveness/safety outcomes for oral TMP/SMT in genital ulcers (mainly chancroid), respiratory tract infections and urinary tract infections (UTIs). Moreover, i.v. TMP/SMT was effective against Pneumocystis jiroveci infection in HIV-infected patients, severe pneumonia and UTIs. In one study, hypersensitivity reactions occurred in 18/52 (34.6%) of HIV-infected patients; 2/52 (3.8%) developed psychosis. Gastrointestinal adverse events were mild and rare. Excipients in i.v. TMP/SMT formulations might be less toxic compared with i.v. TMP/SMX formulations, particularly for children. In conclusion, despite the scarcity of contemporary evidence, available data suggest that TMP/SMT could be an alternative treatment option to TMP/SMX, even in serious infections, when administered intravenously.

Age distribution of cases of 2009 (H1N1) pandemic influenza in comparison with seasonal influenza.

INTRODUCTION: Several aspects of the epidemiology of 2009 (H1N1) pandemic influenza have not been accurately determined. We sought to study whether the age distribution of cases differs in comparison with seasonal influenza. METHODS: We searched for official, publicly available data through the internet from different countries worldwide on the age distribution of cases of influenza during the 2009 (H1N1) pandemic influenza period and most recent seasonal influenza periods. Data had to be recorded through the same surveillance system for both compared periods. RESULTS: For 2009 pandemic influenza versus recent influenza seasons, in USA, visits for influenza-like illness to sentinel providers were more likely to involve the age groups of 5-24, 25-64 and 0-4 years compared with the reference group of >64 years [odds ratio (OR) (95% confidence interval (CI)): 2.43 (2.39-2.47), 1.66 (1.64-1.69), and 1.51 (1.48-1.54), respectively]. Pediatric deaths were less likely in the age groups of 2-4 and <2 years than the reference group of 5-17 years [OR (95% CI): 0.46 (0.25-0.85) and 0.49 (0.30-0.81), respectively]. In Australia, notifications for laboratory-confirmed influenza were more likely in the age groups of 10-19, 5-9, 20-44, 45-64 and 0-4 years than the reference group of >65 years [OR (95% CI): 7.19 (6.67-7.75), 5.33 (4.90-5.79), 5.04 (4.70-5.41), 3.12 (2.89-3.36) and 1.89 (1.75-2.05), respectively]. In New Zealand, consultations for influenza-like illness by sentinel providers were more likely in the age groups of <1, 1-4, 35-49, 5-19, 20-34 and 50-64 years than the reference group of >65 years [OR (95% CI): 2.38 (1.74-3.26), 1.99 (1.62-2.45), 1.57 (1.30-1.89), 1.57 (1.30-1.88), 1.40 (1.17-1.69) and 1.39 (1.14-1.70), respectively]. CONCLUSIONS: The greatest increase in influenza cases during 2009 (H1N1) pandemic influenza period, in comparison with most recent seasonal influenza periods, was seen for school-aged children, adolescents, and younger adults.

Acute Tc-99m DMSA scan for identifying dilating vesicoureteral reflux in children: a meta-analysis.

Controversy exists regarding the type and/or sequence of imaging studies needed during the first febrile urinary tract infection (UTI) in young children. Several investigators have claimed that because acute-phase Tc-99m dimercaptosuccinic acid (DMSA) renal-scan results are abnormal in the presence of dilating vesicoureteral reflux, a normal DMSA-scan result makes voiding cystourethrography (VCUG) unnecessary in the primary examination of infants with UTI. To evaluate the accuracy of acute-phase DMSA scanning in identifying dilating (grades III through V) vesicoureteral reflux documented by VCUG in children with a first febrile UTI, we performed a meta-analysis of the accuracy of diagnostic tests as reported from relevant studies identified through the PubMed and Scopus databases. Patient-based and renal unit-based analyses were performed. Overall, 13 cohort studies were identified. Nine studies involved patients younger than 2 years, 3 involved children aged 16 years or younger, and 1 involved exclusively neonates. Girls constituted 22% to 85% of the involved children. Pooled (95% confidence intervals) sensitivity and specificity rates of DMSA scanning were 79% and 53%, respectively, for the patient-based analysis (8 studies) and 60% and 65% for the renal unit-based analysis (5 studies). The respective areas under the hierarchical summary receiver operating curves were 0.71 and 0.67. Marked statistical heterogeneity was observed in both analyses, as indicated by I(2) test values of 91% and 87%, respectively. Acute-phase DMSA renal scanning cannot be recommended as replacement for VCUG in the evaluation of young children with a first febrile UTI.

Knowledge and practices regarding prevention of infections associated with central venous catheters: a survey of intensive care unit medical and nursing staff.

BACKGROUND: Infections associated with central venous catheters (CVCs) are associated with considerable morbidity and mortality. METHODS: We conducted a survey to evaluate the theoretical knowledge and practices of intensive care unit doctors and nursing staff regarding CVC-related infections. RESULTS: A questionnaire was distributed to 345 doctors and nurses. The response rate was 71.6%. Of the responders, 84.9% worked in public hospitals, 40% had been trained in CVC-related infection issues, and 27% were familiar with the relevant Centers of Disease Control and Prevention guidelines. The mean percentage of correct answers (± standard deviation) on the 3 parts of the questionnaire were 42.9% ± 16.2%, 86.9% ± 9.5%, and 85.4% ± 7.2%. In the subset of questions referring to procedures that were doctors' exclusive responsibility, 13.6% of the doctors answered all questions correctly. Age >37 years, awareness of relevant official guidelines, working in a private hospital, and being a doctor were identified as independent variables associated with high scores in knowledge regarding the prevention of CVC-related infections. Female sex and training in infection prevention were associated with higher scores on the part evaluating adherence to specific practices regarding CVC insertion, whereas being a nurse was associated with higher scores on the part evaluating CVC maintenance. CONCLUSION: Our findings suggest that there is a need for increased theoretical knowledge and improvement in practices regarding CVC care. Educational programs directed at doctors and nurses working in intensive care units may aid this effort.

Serum procalcitonin as a diagnostic marker for neonatal sepsis: a systematic review and meta-analysis.

PURPOSE: To assess the value of serum procalcitonin (PCT) for the differentiation between patients with and without neonatal sepsis. METHODS: We systematically searched PubMed, Scopus, and the Cochrane Library for studies evaluating PCT in neonatal sepsis. PCT had to be measured in neonatal blood samples, at the initial presentation of patients with suspected sepsis, before the administration of antibiotics. We performed a bivariate meta-analysis of sensitivity and specificity, and constructed a hierarchical summary receiver-operating characteristic (HSROC) curve. RESULTS: Overall, 29 studies eligible for inclusion were identified. We analyzed the 16 studies (involving 1,959 neonates) that evaluated PCT in neonates with culture-proven or clinically diagnosed sepsis in comparison with ill neonates with other conditions. The pooled (95% confidence interval) sensitivity and specificity were 81% (74-87%) and 79% (69-87%), respectively. The area under the HSROC curve (AUC) was 0.87. The diagnostic accuracy of PCT seemed higher for neonates with late-onset sepsis (>72 h of life) than for those with early onset sepsis; the AUC for these analyses was 0.95 and 0.78, respectively. However, fewer data were available for late-onset sepsis. High statistical heterogeneity was observed for all analyses. CONCLUSION: Our findings suggest that serum PCT at presentation has very good diagnostic accuracy (AUC = 0.87) for the diagnosis of neonatal sepsis. However, in view of the marked observed statistical heterogeneity, along with the lack of a uniform definition for neonatal sepsis, the interpretation of these findings should be done with appropriate caution.

ß-D-glucan assay for the diagnosis of invasive fungal infections: a meta-analysis.

We aimed to assess the accuracy of measuring serum or plasma (1→3)-ß-D-glucan (BDG) for the diagnosis of invasive fungal infections (IFIs) by means of a meta-analysis of relevant studies. We searched in bibliographic databases for relevant cohort or case-control studies. We primarily compared BDG between patients with proven or probable IFIs (excluding Pneumocystis jirovecii infections), according to the criteria of the European Organization for Research and Treatment of Cancer/Mycoses Study Group or similar criteria, and patients without IFIs (excluding healthy individuals as controls). A total of 2979 patients (594 with proven or probable IFIs), included in 16 studies, were analyzed. The pooled sensitivity of BDG was 76.8% (95% confidence interval [CI], 67.1%-84.3%), and the specificity was 85.3% (95% CI, 79.6%-89.7%). The area under the summary receiver operating characteristic curve was 0.89. Marked statistical heterogeneity was noted. BDG has good diagnostic accuracy for distinguishing proven or probable IFIs from no IFIs. It can be useful in clinical practice, if implemented in the proper setting and interpreted after consideration of its limitations.

Evaluation of a direct test for seasonal influenza in outpatients.

OBJECTIVE: To present our experience regarding the use of a rapid diagnostic test for seasonal influenza A and B. METHODS: We systematically collected and analyzed our data regarding the use of a rapid diagnostic test for seasonal influenza A and B in patients with specific respiratory symptoms that sought medical services, during the time period from 01/01/2009 to 30/05/2009, from a network of physicians (SOS Doctors) who perform house-call visits in the area of Attica, Greece. RESULTS: From the total of 16,335 house-call visits performed during the evaluated period, 3412 (20.8%) were due to respiratory/influenza symptoms; 197 (5.8%) patients were tested for influenza. From the 184 patients with available data regarding the test result, 97 (52.7%) were positive for influenza. Significantly more oseltamivir and less antibiotic treatment were prescribed to patients with positive test result compared with those with a negative test result. Additionally, the impact of the test in the participating physicians' decision making was obvious, as doctors who used the test systematically prescribed significantly more oseltamivir and less antibiotic treatment compared to the doctors who didn't use the test. CONCLUSION: The use of a rapid test for seasonal influenza enabled the targeted treatment with oseltamivir, as well as a reduction in antibiotic treatment, in patients found positive for influenza in our clinical setting.

Inhaled colistin for the treatment of tracheobronchitis and pneumonia in critically ill children without cystic fibrosis.

Data regarding the role of inhaled colistin in critically ill pediatric patients without cystic fibrosis are scarce. Three children (one female), admitted to the intensive care unit (ICU) of a tertiary-care pediatric hospital in Athens, Greece, during 2004-2009 received inhaled colistin as monotherapy for tracheobronchitis (two children), and as adjunctive therapy for necrotizing pneumonia (one child). Colistin susceptible Acinetobacter baumannii and Pseudomonas aeruginosa were isolated from the cases' bronchial secretions specimens. All three children received inhaled colistin at a dosage of 75 mg diluted in 3 ml of normal saline twice daily (1,875,000 IU of colistin daily), for a duration of 25, 32, and 15 days, respectively. All three children recovered from the infections. Also, a gradual reduction, and finally total elimination of the microbial load in bronchial secretions was observed during inhaled colistin treatment in the reported cases. All three cases were discharged from the ICU. No bronchoconstriction or any other type of toxicity of colistin was observed. In conclusion, inhaled colistin was effective and safe for the treatment of two children with tracheobronchitis, and one child with necrotizing pneumonia. Further studies are needed to clarify further the role of inhaled colistin in pediatric critically ill patients without cystic fibrosis.

Fosfomycin versus other antibiotics for the treatment of cystitis: a meta-analysis of randomized controlled trials.

BACKGROUND: Cystitis is a common infection. The alarmingly high resistance rates exhibited by contemporary uropathogens necessitate the re-evaluation of old antibiotics. OBJECTIVES: To evaluate the effectiveness and safety of fosfomycin compared with other antibiotics for the treatment of patients with cystitis. METHODS: We performed a meta-analysis of randomized controlled trials (RCTs), generated from searches performed in PubMed, Scopus and Cochrane CENTRAL, which involved patients with cystitis treated with fosfomycin versus other antibiotics. RESULTS: Twenty-seven trials (eight double-blind) were included. Sixteen of these 27 trials involved exclusively non-pregnant female patients, 3 involved adult mixed populations of older age, 5 involved pregnant patients and 3 involved paediatric patients. Regarding clinical success, no difference was found in the comprehensive analysis regarding all comparators combined [10 RCTs, 1657 patients, risk ratio (RR) = 1.00, 95% confidence interval (CI) = 0.98-1.03] in trials involving non-pregnant females and in trials involving mixed populations. Insufficient relevant data were provided from trials involving paediatric and pregnant patients. No difference between fosfomycin and comparators was also found in all comparisons regarding the remaining effectiveness outcomes (namely microbiological success/relapse/re-infection). Fosfomycin had a comparable safety profile with the evaluated comparators in non-pregnant women, mixed and paediatric populations, whereas it was associated with significantly fewer adverse events in pregnant women (4 RCTs, 507 patients, RR = 0.35, 95% CI = 0.12-0.97). CONCLUSIONS: In the era of high drug resistance rates, reported even among community-acquired uropathogens, fosfomycin may provide a valuable alternative option for the treatment of cystitis in non-pregnant and pregnant women and in elderly and paediatric patients.

Patients included in randomised controlled trials do not represent those seen in clinical practice: focus on antimicrobial agents.

Clinicians rely on the findings of randomised controlled trials (RCTs) to formulate clinical decisions regarding individual patients. We examined whether patients included in RCTs focusing on antimicrobial agents are representative of those encountered in real-life clinical situations. PubMed was searched for RCTs referring to the field of infectious diseases. Data regarding the exclusion criteria of the identified RCTs were extracted and critically evaluated. In total, 30 trials (17 referring to respiratory tract, 5 to skin and soft-tissue, 4 to intra-abdominal, 2 to gynaecological and 2 to bloodstream infections) were included in the study. All retrieved RCTs reported extensive exclusion criteria. After comparing in a qualitative manner (based on our clinical experience) the eligible patient population in the identified RCTs with the respective population that would be encountered in general practice, it was observed that the abovementioned patient populations differ considerably. In conclusion, RCTs in the field of infectious diseases use extensive and stringent exclusion criteria, a fact that may lead to considerable difference between the patient populations of RCTs and those viewed in clinical practice. The application of the findings of RCTs to the care of individual patients should be performed cautiously.

Effectiveness and safety of neuraminidase inhibitors in reducing influenza complications: a meta-analysis of randomized controlled trials.

BACKGROUND: Several studies suggest that neuraminidase inhibitors (NIs) can reduce the duration of influenza symptoms. However, data regarding their effectiveness in reducing influenza complications are scarce. METHODS: We evaluated the effectiveness of NIs in reducing influenza complications and mortality of patients with seasonal influenza, by performing a meta-analysis of randomized controlled trials (RCTs), retrieved from PubMed, Cochrane Central Register of Controlled Trials and Scopus databases, comparing NIs with placebo. RESULTS: Eleven RCTs (10 double-blind) were included; 8 involved adults/adolescents. In total, 5315 patients were included; 3491 (65.7%) with confirmed infection. Total influenza-related complications were significantly less likely in otherwise healthy patients with confirmed influenza infection that were treated with NIs versus placebo [7 RCTs, 2621 patients, risk ratio (RR) = 0.74, 95% confidence interval (CI) = 0.58-0.95] This finding was more pronounced in high-risk patients [4 RCTs, 475 patients, RR = 0.37, 95% CI = 0.24-0.59]; P < 0.01 for the chi(2) test for subgroup differences. In the comparisons regarding individual complications, a trend in favour of NIs was observed. Acute otitis media was significantly less likely in patients with confirmed influenza infection treated with NIs versus placebo (3 RCTs, 1124 patients, RR = 0.50, 95% CI = 0.30-0.85). No differences were found in the comparisons regarding the safety outcomes. No deaths were observed in trials that reported on mortality. CONCLUSIONS: NIs seem to be effective in reducing total influenza-related complications in otherwise healthy and high-risk patients, and have an acceptable safety profile. However, RCTs providing separate data for mild to serious complications and detailed reporting of adverse events and mortality are needed.

Treatment options for 2009 H1N1 influenza: evaluation of the published evidence.

We evaluated the evidence regarding the effectiveness of various treatment strategies used for 2009 H1N1 influenza by reviewing available relevant studies. In total, 22 studies (15 cohort studies involving >10 patients, 5 cohort studies with < or = 10 patients and 2 case reports) were included. A total of 3020 patients [1068 (35.4%) critically ill, 1722 (57.0%) hospitalised and 230 (7.6%) outpatients, including 909 (30.1%) children] were involved. Notably, 487 (16.1%) were obese [body mass index (BMI) >30)], 362 (12.0%) had asthma or chronic obstructive pulmonary disease and 255 (8.4%) were pregnant. Antiviral treatment was administered to 1622 patients (53.7%), of whom 661 (40.8%) received oseltamivir monotherapy. Corticosteroids were administered in 323 (31.8%) of 1016 patients for whom relevant data were available. Similarly, 633 (85.0%) of 745 patients received antibiotics. Comparative data from the largest included study (involving 1088 patients) indicated that administration of antivirals within 2 days from symptom onset was significantly associated with reduced mortality (P<0.001). In summary, the scarcity of comparative available data hampered the establishment of any firm conclusions regarding the benefit that various treatment strategies may confer to patients with 2009 H1N1 influenza. Studies with a comparative design, as well as randomised studies are needed to clarify further this issue of major importance.