Stavros Athanasiou

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.

Do Psychological Variables Affect Early Surgical Recovery

Background Numerous studies have examined the effect of psychological variables on surgical recovery, but no definite conclusion has been reached yet. We sought to examine whether psychological factors influence early surgical recovery. Methods We performed a systematic search in PubMed, Scopus and PsycINFO databases to identify studies examining the association of preoperative psychological variables or interventions with objectively measured, early surgical outcomes. Results We identified 16 eligible studies, 15 of which reported a significant association between at least one psychological variable or intervention and an early postoperative outcome. However, most studies also reported psychological factors not influencing surgical recovery and there was significant heterogeneity across the studies. Overall, trait and state anxiety, state anger, active coping, subclinical depression, and intramarital hostility appeared to complicate recovery, while dispositional optimism, religiousness, anger control, low pain expectations, and external locus of control seemed to promote healing. Psychological interventions (guided relaxation, couple support visit, and psychiatric interview) also appeared to favor recovery. Psychological factors unrelated to surgical outcomes included loneliness, perceived social support, anger expression, and trait anger. Conclusion Although the heterogeneity of the available evidence precludes any safe conclusions, psychological variables appear to be associated with early surgical recovery; this association could bear important implications for clinical practice. Large clinical trials and further analyses are needed to precisely evaluate the contribution of psychology in surgical recovery.

Imiquimod for treatment of vulvar and vaginal intraepithelial neoplasia

We searched PubMed, Scopus, Web of Science, LILACS, EMBASE, and Cochrane Library databases to assess the effectiveness and safety of 5% imiquimod cream in the treatment of vulvar and vaginal intraepithelial neoplasia. From the results of the 17 relevant articles identified (1 reported on a randomized controlled trial, 10 reported on case series, and 6 were case reports), 26% to 100% of patients had complete regression, 0% to 60% had partial regression, and 0% to 37% experienced recurrence. The most common adverse events were local burning and soreness, but not severe enough for patients to discontinue treatment. From these reports imiquimod treatment leads to complete response in a considerable percentage of patients, and those who experience partial response will require less extensive excision. Treating vulvar and vaginal intraepithelial neoplasia with 5% imiquimod cream therefore appears to be promising.

Safety of Hepatitis B, Pneumococcal Polysaccharide and Meningococcal Polysaccharide Vaccines in Pregnancy

Immunization during pregnancy has the potential to protect the mother and the newborn from preventable diseases. Current recommendations suggest that inactivated vaccines might be considered during pregnancy when the benefits outweigh the risks.In this review, we aimed to evaluate the safety of hepatitis B (HB) vaccine, pneumococcal polysaccharide vaccine (PPSV) and meningococcal polysaccharide vaccine (MPSV) administration during pregnancy by systematically reviewing the available evidence in PubMed and Scopus databases, as well as postmarketing surveillance data (including the Vaccine Adverse Event Reporting System [VAERS] database). A total of 18 studies were eligible for inclusion in the review. Six studies provided data on HB vaccine, six on PPSV and three on MPSV; three additional studies compared PPSV with MPSV. Additionally, 91 reports on vaccinations of pregnant women were identified from postmarketing surveillance data (88 on HB vaccine, 2 on PPSV, 1 on MPSV). The most common complaints were local reactions, including tenderness and swelling. Overall, immunization during pregnancy did not seem to be associated with a teratogenic effect on the fetus, preterm labour or spontaneous abortion. However, the lack of randomized, placebo-controlled trials, or even large cohort studies, in addition to the inherent limitations of the reviewed observational studies with small statistical power, precluded safe conclusions. Large, prospective, population-based cohort studies are needed to elucidate this issue.

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.

Evaluation of Antimicrobial Susceptibility of Enterobacteriaceae Causing Urinary Tract Infections in Africa

ABSTRACT Our objective was to evaluate the antimicrobial susceptibility of Enterobacteriaceae causing urinary tract infections (UTIs) in adults in Africa. The PubMed database was systematically searched to identify relevant studies published after 2000. Google, World Health Organization, and African Field Epidemiology networks were also searched. Twenty-eight studies, accounting for 381,899 urine isolates from 14 African countries, met the inclusion criteria. Escherichia coli, Klebsiella spp., and Proteus spp. were the most commonly encountered uropathogens. Cefotaxime, imipenem, fosfomycin, and ciprofloxacin were the antibiotics with the highest activity against E. coli isolates from outpatients, with susceptibility being 92 to 99, 100, 100, and 68 to 91%, respectively. The susceptibility among Klebsiella spp. isolates from outpatients varied from 80 to 100% for amikacin and from 53 to 100% for ciprofloxacin, while susceptibility was 74 to 78, 97, and 77% for ciprofloxacin, amikacin, and fosfomycin, respectively, among Klebsiella species isolates from inpatients or patients with hospital-acquired UTIs. With regard to Proteus spp., the highest activity was observed among fluoroquinolones; 71 to 100% of the P. mirabilis isolates were susceptible to ciprofloxacin in four studies, and 74 to 100% of the P. vulgaris isolates were susceptible to ofloxacin in two studies. The currently available evidence suggests that the antimicrobial susceptibility patterns of Enterobacteriaceae uropathogens in African countries were similar to those in countries of southeast Europe. Further original studies are warranted from African countries for which there is limited published data.

Urinary tract infections after pelvic floor gynecological surgery: prevalence and effect of antimicrobial prophylaxis. A systematic review

We evaluated the prevalence of urinary tract infection (UTI) after pelvic floor operations for non-malignant etiology and the effectiveness of antibiotic prophylaxis. This was made possible by a review of the evidence from relevant randomized controlled trials (RCTs). Nineteen out of 879 initially identified studies met the criteria for inclusion in our review. Four RCTs compared an antibiotic prophylactic regimen with placebo, 11 two different prophylactic antibiotic regimens, and four had three different treatment arms. Among placebo recipients undergoing pelvic floor surgery, 10–64% developed UTI. In contrast, UTI after pelvic floor gynecological surgery occurred in 0–15% of the patients who received cephalosporins as antibiotic prophylaxis; the likelihood for postoperative UTI was higher for patients receiving cotrimoxazole (28%), ampicillin/sulbactam (13.6%), metronidazole plus ampicillin (20%), metronidazole (10–22.7%), or ciprofloxacin (27.2%). The use of a cephalosporin as perioperative antimicrobial prophylaxis is the optimal regimen in preventing UTIs after pelvic floor surgery.

Early switch to oral versus intravenous antimicrobial treatment for hospitalized patients with acute pyelonephritis: a systematic review of randomized controlled trials

ABSTRACT Background: Acute pyelonephritis is a common infection with significant morbidity and mortality, particularly in pediatric populations. Early-switch strategies (from intravenous to oral treatment) may be an acceptable or even preferred option in the treatment of patients with acute pyelonephritis in terms of effectiveness and safety and can also reduce the economical burden associated with pyelonephritis. Objective: We sought to evaluate the effectiveness and safety of early-switch strategies in hospitalized patients with acute uncomplicated pyelonephritis. Methods: We searched in PubMed, Cochrane Central Register of Controlled Trials, and Scopus to identify randomized controlled trials (RCTs) that compared intravenous antibiotic regimens to regimens including an early switch to oral (after initial intravenous) treatment. Results: Eight RCTs (6 in children) were eligible for inclusion. In 5 RCTs the intravenous antibiotic treatment arms were not switched to oral treatment until the end of the study while in the remaining 3 RCTs the intravenous arms were switched late to oral treatment (after 5–10 days). Data regarding the incidence of renal scars, microbiological eradication, clinical cure, reinfection, persistence of acute pyelonephritis, and adverse events were provided in 4 (all pediatric trials), 6 (4 pediatric), 4 (2 pediatric), 5 (3 pediatric), 3 (1 pediatric), and 5 RCTs (3 pediatric), respectively. There were no differences regarding the above outcomes between the two compared treatment regimens in either pediatric or adult populations. Conclusion: Early switch to oral antibiotic strategies seem to be as effective and safe as intravenous regimens for the treatment of hospitalized patients with acute pyelonephritis. These findings suggest that there is probably a potential to decrease the duration of intravenous treatment by 4–11 days in hospitalized patients with acute pyelonephritis without compromising their outcomes.

Adhesive strips for the closure of surgical incisional sites: a systematic review and meta-analysis.

Background. The authors evaluated the available evidence regarding the use of adhesive strips for the management of surgical incisions and compared them with sutures and other closure materials. Study design. Systematic review and meta-analysis of randomized controlled trials (RCTs). Results. Twelve RCTs studying 1317 incisions in 1023 patients were included. No difference was found regarding the development of infection (odds ratio [OR] = 0.47; 95% Confidence interval [CI] = 0.12-1.85), dehiscence (OR = 1.22; 95% CI = 0.32-4.64), and overall cosmetic result (standardized mean difference = 0.01; 95% CI = −0.19 to 0.20). Closure with strips resulted in significantly lower incidence of redness (OR = 0.57; 95% CI = 0.37-0.89). The available data on pain, need for resuturing, swelling, patient satisfaction, and closure time with the use of strips could not be synthesized; however, regarding the latter 2 outcomes, application of strips seemed favorable. There was significant heterogeneity among the studies. Conclusions. The findings suggest that adhesive strips may be an efficient closure material for certain small-length incisions. Further research is warranted on outcomes such as dehiscence and the need for resuturing.

Clinical and urodynamic parameters associated with history of urinary tract infections in women: a prospective study

Objectives. To evaluate the association of various clinical and urodynamic variables with history of urinary tract infections (UTIs) in women. Methods. A prospective study of 2,081 women referred to a urogynecologic clinic between June 2000 and November 2005 for investigation of lower urinary tract symptoms. Results. 144 women reported history of UTI(s) within the last year from the visit to the clinic, and 91 had recurrent episodes (≥3 per year). The multivariable analysis showed that urge incontinence (odds ratio (OR) = 2.23, 95% confidence interval (CI): 1.46–3.42), suprapubic pain (OR = 4.12, 95% CI: 2.21–7.67), and low maximum flow rate during voiding cystometry (OR = 0.96, 95% CI: 0.94–0.98) were associated with UTIs. Conclusions. Our results suggest that urodynamic testing does not help in identifying specific urogynecologic mechanisms that could improve medical and/or surgical management or prevent recurrent UTI.