Zeynel Abidin Yargic

Effectiveness and safety of Saccharomyces boulardii for acute infectious diarrhea

Introduction: Acute diarrhea continues to be a leading cause of morbidity, hospitalization and mortality worldwide and probiotics have been proposed as a complementary therapy in the treatment of acute diarrhea. Regarding the treatment of acute diarrhea, a few probiotics including Saccharomyces boulardii seem to be promising therapeutic agents. Areas covered: We performed a systematic review and meta-analysis regarding the use of S. boulardii in the treatment of acute infectious diarrhea with relevant studies that searched with the PubMed, Embase, Scopus, Google Scholar, the Cochrane Controlled Trials Library, and the Cochrane Database of Systematic Reviews through October 2011. This review describes the effects of S. boulardii on the duration of diarrhea, the risk of diarrhea during the treatment (especially at the third day) and duration of hospitalization in patients with acute infectious diarrhea. This review also focused on the potential effects of S. boulardii for acute infectious diarrhea due to different etiological causes. Expert opinion: S. boulardii significantly reduced the duration of diarrhea approximately 24 h and that of hospitalization approximately 20 h. S. boulardii shortened the initial phase of watery stools; mean number of stools started to decrease at day 2; moreover, a significant reduction was reported at days 3 and 4. This systematic review and meta-analysis of the efficacy of S. boulardii in the treatment of acute infectious diarrhea show that there is strong evidence that this probiotic has a clinically significant benefit, whatever the cause, including in developing countries. Therefore, with S. boulardii, the shortened duration of diarrhea and the reduction in hospital stay result in social and economic benefits.

Current knowledge regarding the investigational 13-valent pneumococcal conjugate vaccine

The introduction of a 7-valent pneumococcal conjugate vaccine (PCV-7) into the routine childhood vaccination schedule has been shown to be effective in preventing invasive pneumococcal disease (IPD), pneumonia, otitis media and meningitis in infants and young children as determined by epidemiological surveillance studies. There has been a rise in IPD due to nonvaccine serotypes; however, this rise is small compared with the overall reduction in IPD. Non-PCV-7 serotypes and vaccine-related serotypes, such as serotypes 1, 5, 7F, 6A and 19A, have also been reported to cause IPD in some parts of the world where morbidity and mortality from pneumococcal disease are higher. An investigational 13-valent pneumococcal conjugate vaccine (PCV-13) uses CRM197 as a carrier, similar to the current PCV-7, and covers serotypes 1, 3, 5, 6A, 7F and 19A, in addition to the serotypes of PCV-7 (serotype 4, 6B, 9V, 14, 18C, 19F and 23F). PCV-13 is safe and well tolerated with other pediatric vaccines in infants according to clinical trials. IgG anticapsular polysaccharide-binding concentrations and opsonophagocytic assay responses are similar and noninferior between PCV-13 and PCV-7 and, according to immunogenicity studies, PCV-13 has more potential to protect against pneumococcal diseases with the additional six serotypes. With the addition of these new serotypes, it could be possible to cover potential pneumococcal serotypes causing IPD throughout the world. The cost of the vaccine, its length of duration, optimal scheduling, combination and boosting with PCV-7 are still unresolved issues. Assessment of the vaccine’s effectiveness and efficacy following potential licensure will require carefully designed cohort and case–control studies that can assess the indirect effects of PCV-13.

Pneumococcal conjugated vaccines: impact of PCV-7 and new achievements in the postvaccine era

Pneumococcal disease is a major health problem worldwide. Large, rapid declines in overall invasive pneumococcal disease and mucosal disease in children, reductions in vaccine-type disease in unvaccinated children and adults (indirect effects) and significant drops in antibiotic-resistant infections were observed after the introduction of a safe, available and immunogenic seven-valent pneumococcal vaccine. The determination of vaccine efficacy is a complex process, which includes efficacy, immunogenicity, safety, cross-reactivity, indirect effects and substantial geographic variation in serotype coverage. In this report, we perform an overview of the literature on current, investigational and potential candidate pneumococcal conjugated vaccines (PCVs). Every country should have its own strong and sustained surveillance system implemented to monitor the effects of vaccination on the frequency of vaccine and nonvaccine serotypes for invasive or mucosal disease, nasopharyngeal carriage and the indirect effects before and after introduction of PCV. New PCVs (PHiD-CV and PCV-13) may provide even greater coverage worldwide, especially in developing countries. Vaccine experts’ efforts are currently focused on developing alternative vaccine strategies against pneumococcal infections, especially the development of vaccines based on pneumococcal proteins.

Pneumococcal conjugated vaccine: PHiD-CV

At the beginning of a new century, we have gained significant achievements against pneumococcal infections by using conjugated pneumococcal vaccines. In January 2009, the EMEA issued a positive opinion about, and recommended the approval of, GlaxoSmithKline’s pediatric pneumococcal candidate vaccine, which is indicated for active immunization against invasive pneumococcal disease (IPD) and acute otitis media caused by Streptococcus pneumoniae in infants and children from 6 weeks up to 2 years of age. The approved 10-valent pneumococcal vaccine (PHiD-CV) contains all serotypes in 7-valent pneumococcal conjugate vaccine (PCV-7) plus serotypes 1, 5 and 7F. Protein D from nontypeable Haemophilus influenzae is the carrier protein for eight serotypes, while tetanus and diphtheria toxins are in the carrier proteins for the remaining two serotypes. It has also been proved that PHiD-CV is immunogenic, safe and well-tolerated in children. This vaccine can be coadministered with routinely used pediatric vaccines. Noninferiority criteria of PHiD-CV compared with PCV-7 were established in shared serotypes, except for serotypes 6B and 23F, and PHiD-CV is immunogenic for additional serotypes as assessed by the percentage of subjects with antibody concentrations. PHiD-CV is also immunogenic for ten serotypes as assessed by post-primary and post-booster dose opsonophagocytic activity responses. Vaccine efficacy against IPD and other conditions should be monitored for shared serotypes and also additional serotypes during the postmarketing period. Optimal scheduling, safety and immunogenicity data in children with different risk factors for IPD, or whether it will provide herd immunity, are the questions waiting for answers in the postmarketing period. Further studies are needed to assess the potential advantages of protein D as a carrier and the potential efficacy of this new vaccine against H. influenzae. The potential public health efficacy of PHiD-CV in low-income countries, where IPD and pneumonia are a major public health problem, is a major concern.

Tigecycline treatment of multi-drug-resistant Corynebacterium jeikeium infection in a child with relapsing and refractory acute lymphoblastic leukemia.

Corynebacterium jeikeium has been recognized as an important cause of infection, particularly among neutropenic patients who have central venous catheter (CVC). Routine use of tigecycline in children is not yet approved. Here in we present a child with relapsed‐refractory lymphoblastic leukemia who was successfully treated with tigecyline due to multi‐drug‐resistant C. jeikeium sepsis without removal of CVC. Our case highlights the use of tigecycline where there are no alternatives. Further studies regarding the efficacy and safety of tigecycline in pediatric patients are needed. Pediatr Blood Cancer. 2010;55:349–351.

27th Annual Meeting of the European Society for Pediatric Infectious Disease.

The 27th Annual Meeting of the European Society for Pediatric Infectious Disease (ESPID) was held in Brussels, Belgium, on 8–13 June 2009. Europe’s largest pediatric infectious disease congress brought international pediatricians and experts on pediatric infectious disease and vaccine together. Owing to the numerous pediatric infectious topics and issues that were discussed, in this report we summarize the current knowledge about pneumococcal disease and pneumococcal conjugate vaccines (PCVs). The main topics covered are current pneumococcal seroepidemiology after the introduction of the 7-valent conjugated pneumococcal vaccine (PCV7), the efficacy and immunogenicity of a reduced-dose schedule of PCV7, and the effectiveness of PCV7 against invasive pneumococcal disease, otitis media and related conditions, pneumonia, and nasopharyngeal carriage. New studies, including that on the cost–effectiveness of the currently licensed 10-valent pneumococcal vaccine, which uses protein D from the nontypeable Haemophilus influenzae protein (PHiD-CV) and investigational PCVs (investigational 13-valent PCV [PCV13] and 11-valent PCV [PCV11]), were also presented. Next year, the 28th ESPID meeting will be held in Nice, France, on 4–8 June 2010. We will have a chance to see and evaluate, after the PCV7 and PHiD-CV era, current efficacy studies about new vaccines and investigational vaccines. With the 2015 key millennium development goalonly 5 years away, we need to accelerate the introduction of current vaccines and also evaluate newcomer vaccines in order to reduce the mortality rate among children younger than 5 years of age by two-thirds.

In vitro activity of ertapenem and other carbapenems against extended-spectrum beta-lactamase producing Escherichia coli and Klebsiella pneumoniae clinical isolates in a tertiary care center in Turkey.

Objective: To evaluate the in vitro effect of ertapenem, imipenem and meropenem in clinical isolates of extended-spectrum β-lactamase (ESBL)-producing strains of Escherichia coli and Klebsiella pneumoniae. Design/methods: We studied 82 consecutive clinical isolates of ESBL-producing E. coli (n = 49) and K. pneumonia (n = 33) between February 2006 and September 2007. The minimum inhibitory concentration for each carbapenem was determined using the agar dilution method. Results: Eighty two consecutive microorganisms from sterile sites were evaluated. A total of 48.8% of patients had a history of surgical intervention, 78.0% needed urinary catheterization, 57.3% required vascular access and 40.3% mechanical ventilation; and 70.7% had a history of ICU stay. High resistance rates were shown for both E. coli and K. pneumoniae against cefepime (81.7%), ciprofloxacin (50.9%), tetracycline (75.0%), co-trimoxazole (47.4%), and gentamicin (48.7%). In addition, most K. pneumoniae and E. coli isolates were susceptible to amikacin (78.3%) and piperacilline-tazobactam (91.5%). Meropenem and imipenem showed activity against 100% of the isolates. Ertapenem showed activity against 100% of K. pneumoniae isolates, against 95.9% of E. coli isolates and against 97.5% of the 82 ESBL-producing microorganisms. Two E. coli isolates showed ertapenem resistance. Conclusion: In recent literature, carbapenems were the most active antimicrobial agents against ESBL-producing Enterobacteriaceae, as in our study. This is the first study on the in vitro activity of ertapenem against ESBL-producing E. coli and K. pneumoniae conducted in Turkey. In view of the serious infections caused by ESBL-producing microorganisms, therapeutic interventions are still problematic in serious clinical conditions. Ertapenem may be a good choice for treatment, with the additional advantage of being a once a day regimen.