High-alert medications for hospitalised paediatric patients - a two-step survey among paediatric clinical expert pharmacists in Germany.

Paediatric patients are more vulnerable to be harmed by medication errors compared to adults due to pharmacokinetic and pharmacodynamic changes in their development, individual dosing calculations, and manipulation of ready to-use products intended for adult patients. According to the Institute of Safe Medication Practices, there are some "drugs that bear a heightened risk of causing significant patient harm when they are used in error"; these drugs are called high-alert medications (HAM). The two-step survey among paediatric clinical expert pharmacists presented here aimed to compile a nation-wide HAM list. To provide detailed guidance, this survey followed a drugbased approach, resulting in specific potential drug related problems (DRPs) and associated recommendations for prevention. In contrast to this approach, in the first round of the survey two drug classes were included that both were rated as HAM (i.e.chemotherapy and parenteral nutrition). Twenty single drugs were identified as HAM, 65% of which were cardiovascular or neurological drugs. The paediatric expert pharmacists mentioned in total 216 potential DRPs; in particular, they identified potential administration-related problems (28% of all DRPs), dosing-related problems (26%), and drug-choice-related problems (18%, e.g.drug confusion and drug monitoring). Moreover, they suggested 275 potential interventions to address these DRPs. Two thirds of all interventions dealt with the preparation by the hospital pharmacy, standardisation of processes (e.g.labelling), and education or training. In conclusion, this survey provided a German paediatric high-alert medication list from a paediatric pharmacist point of view. Moreover, the experts mentioned for the first time specific potential DRPs and associated interventions to guide a local multidisciplinary approach for preventing medication-related harm in children.

The prevalence of 'triple whammy' prescriptions in surgical inpatients and associated pharmacist recommendations.

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are beneficial in surgical settings, they may however lead to adverse drug reactions including decreased renal function, a risk, which is exacerbated by combination with other nephrotoxics, and particularly when NSAIDs are given as part of a so-called 'Triple Whammy' (TW) with diuretics and renin-angiotensin system blockers. The objective of this study was to identify the prevalence of TW-prescriptions in a surgical inpatient setting and to document the changes in renal function after pharmacist recommendations. A prospective, observational single centre pilot study was performed using a series of eleven weekly Point-Prevalence Analyses (PPA). Adult surgical inpatients were screened for a TW-prescription by a clinical pharmacist, who made one of two recommendations on identification of a TW: for patients with eGFR > 60 ml/min/1.73m² close monitoring of renal function; for patients with eGFR ≤ 60 ml/min/1.73m² discontinuation of NSAID. A TW was identified in 18 of 317 patients (prevalence 5.7%; mean age 75 years). NSAID discontinuation was recommended for 7/18 patients (39%) and implemented for six (33%). In cases where the NSAID was de-prescribed, an improvement in renal function until the time of discharge was observed, whilst in patients with eGFR > 60 ml/min/1.73m² for whom monitoring was recommended eGFR remained stable. TW-prescriptions were found to be a potential problem in the studied group of older surgical inpatients. Clinical pharmacists are well placed to identify patients who are prescribed a TW, and to advise on the management of these patients.

Assessment of vaccination coverage of adolescents aged 16-18 years with an innovative electronic immunization record system.

OBJECTIVES: To measure vaccine coverage among adolescents aged 16-18 years who participated in the National Defense Preparation Day in the Aquitaine region using the free electronic immunization record. PATIENTS AND METHODS: We considered adolescents aged 16-18 years who participated in the National Defense Preparation Day in the Aquitaine region from April to October 2013. All participants received a letter explaining how to create an electronic immunization record. Those records were then validated by checking data against the copies of the vaccination cards brought by participants on the day they attended. Vaccination coverage was estimated for eight vaccinations according to the cumulative number of doses registered and vaccines recommended during childhood. RESULTS: Among the 18,714 participants, 9636 agreed to create an electronic immunization record of which 2781 were validated. Vaccination coverage was˃90% for tuberculosis, diphtheria-tetanus-poliomyelitis, measles-mumps-rubella, and Haemophilus influenzae type B, and˂90% for pertussis, hepatitis B, meningococcal C disease, and human papillomavirus. These coverage rates were close to those reported in other available sources. CONCLUSION: Our study calls attention to the insufficient vaccination of adolescents for pertussis, HBV, meningococcal C disease, and HPV. The absence of a system that routinely provides the vaccination status of this population is a major public health issue in France. The use of an electronic immunization record was innovative, but this tool is not extensively used in the general population and has been evaluated by Santé publique France (the French national public health agency).

[Maxillary sinus infection by Bacillus licheniformis: a case report from Djibouti]. / Sinusite maxillaire due à Bacillus licheniformis: à propos d'un cas survenu à Djibouti.

Aerobic, spore-forming gram-positive Bacillus spp infections are rare and reported mainly in immunocompromised hosts. We report a case of acute unilateral maxillary sinusitis, caused by Bacillus licheniformis, in a 35-year-old French soldier stationed in Djibouti. It was easily identifiable due to its typical culture and resistance profile. This case is interesting for two reasons: first, it is, to our knowledge, the first case of sinusitis attributed to this microbe, and second, it has rarely been described in immunocompetent patients without altered skin or mucous membranes.

Surveillance of adverse events following vaccination in the French armed forces, 2011-2012.

OBJECTIVES: French military personnel are subject to a compulsory vaccination schedule. The aim of this study was to present the results of surveillance of vaccine adverse events (VAEs) reported from 2011 to 2012 in the French armed forces. STUDY DESIGN: VAEs were surveyed among all French armed forces from 2011 to 2012 by the epidemiological departments of the military health service. For each case, a notification form providing patient and clinical information was provided. METHODS: Case definitions were derived from the French drug safety guidelines. Three types of VAE were considered: non-serious, serious and unexpected. Incidence rates were calculated by relating VAEs to the number of vaccine doses delivered. RESULTS: In total, 161 VAE cases were reported. The overall VAE reporting rate was 24.6 VAEs per 100,000 doses, and the serious VAE rate was 1.3 per 100,000 doses (nine cases). The serious VAEs included two cases of Guillain-Barré syndrome, one case of optic neuritis, one case of a meningeal-like syndrome, one case of rheumatoid purpura, one case of acute asthma and three cases of fainting. The highest rates of VAE were observed with the Bacille Calmette-Guérin vaccine (BCG) (482.3 per 100,000 doses), inactivated diphtheria-tetanus-poliovirus with acellular pertussis vaccine (dTap-IPV) (106.1 per 100,000 doses) and meningococcal quadrivalent glycoconjugate vaccine (MenACWY-CRM) (39.3 per 100,000 doses). CONCLUSIONS: The global rates of VAE observed in 2011 and 2012 confirm the increase that has been observed since 2009 in the French armed forces, which could reflect improved practitioner awareness about VAEs and the use of certain vaccines added to the vaccination schedule recently (dTap-IPV in 2008 and MenACWY-CRM in 2010). VAEs appear to be relatively rare, particularly serious VAEs, which indicates acceptable tolerance of vaccines.

Decline in antibiotic resistance and changes in the serotype distribution of Streptococcus pneumoniae isolates from children with acute otitis media; a 2001-2011 survey by the French Pneumococcal Network.

Streptococcus pneumoniae is an important cause of acute otitis media (AOM). The aim of this study was to evaluate trends in antibiotic resistance and circulating serotypes of pneumococci isolated from middle ear fluid of French children with AOM during the period 2001-2011, before and after the introduction of the PCV-7 (2003) and PCV-13 (2010) vaccines. Between 2001 and 2011 the French pneumococcal surveillance network analysed the antibiotic susceptibility of 6683 S. pneumoniae isolated from children with AOM, of which 1569 were serotyped. We observed a significant overall increase in antibiotic susceptibility. Respective resistance (I+R) rates in 2001 and 2011 were 76.9% and 57.3% for penicillin, 43.0% and 29.8% for amoxicillin, and 28.6% and 13.0% for cefotaxime. We also found a marked reduction in vaccine serotypes after PCV-7 implementation, from 63.0% in 2001 to 13.2% in 2011, while the incidence of the additional six serotypes included in PCV-13 increased during the same period, with a particularly high proportion of 19A isolates. The proportion of some non-PCV-13 serotypes also increased between 2001 and 2011, especially 15A and 23A. Before PCV-7 implementation, most (70.8%) penicillin non-susceptible pneumococci belonged to PCV-7 serotypes, whereas in 2011, 56.8% of penicillin non-susceptible pneumococci belonged to serotype 19A. Between 2001 and 2011, antibiotic resistance among pneumococci responsible for AOM in France fell markedly, and PCV-7 serotypes were replaced by non-PCV-7 serotypes, especially 19A. We are continuing to assess the impact of PCV-13, introduced in France in 2010, on pneumococcal serotype circulation and antibiotic resistance.

Clinical relevance of different dose calculation strategies for mediastinal IMRT in Hodgkin's disease.

BACKGROUND AND PURPOSE: Conventional algorithms show uncertainties in dose calculation already for three-dimensional conformal radiotherapy (3D-CRT). Intensity-modulated radiotherapy (IMRT) might even increase these. We wanted to assess differences in dose distribution for pencil beam (PB), collapsed cone (CC), and Monte Carlo (MC) algorithm for both 3D-CRT and IMRT in patients with mediastinal Hodgkin lymphoma. PATIENTS AND METHODS: Based on 20 computed tomograph (CT) datasets of patients with mediastinal Hodgkin lymphoma, we created treatment plans according to the guidelines of the German Hodgkin Study Group (GHSG) with PB and CC algorithm for 3D-CRT and with PB and MC algorithm for IMRT. Doses were compared for planning target volume (PTV) and organs at risk. RESULTS: For 3D-CRT, PB overestimated PTV(95) and V(20) of the lung by 6.9% and 3.3% and underestimated V(10) of the lung by 5.8%, compared to the CC algorithm. For IMRT, PB overestimated PTV(95), V(20) of the lung, V(25) of the heart and V(10) of the female left/right breast by 8.1%, 25.8%, 14.0% and 43.6%/189.1%, and underestimated V(10) of the lung, V(4) of the heart and V(4) of the female left/right breast by 6.3%, 6.8% and 23.2%/15.6%, compared to MC. CONCLUSION: The PB algorithm underestimates low doses to the organs at risk and overestimates dose to PTV and high doses to the organs at risk. For 3D-CRT, a well-modeled PB algorithm is clinically acceptable; for IMRT planning, however, an advanced algorithm such as CC or MC should be used at least for part of the plan optimization.

[Influenza A(H1N1)v virus infection in infants less than 6 months of age in southwestern France]. / Grippe A(H1N1)v chez les nourrissons de moins de 6 mois en Aquitaine.

OBJECTIVE: We evaluated the severity of influenza A(H1N1)v clinical forms among infants less than 6 months of age. This population group was considered a high-risk group, so all people around them should be vaccinated first. PATIENTS AND METHODS: In south-western France in Aquitaine, we collected all infants less than 6 months of age during a period between the 6th September 2009 and the 6th January 2010 with influenza A(H1N1)v confirmed by PCR. For each of them, the risk factors, clinical presentation, hospitalization, and course of, the disease were identified. We compared two groups: children under 3 months and infants aged 3-6 months. RESULTS: We identified 74 infants. The average age was 3 months. Sixteen infants had at least 1 risk factor: 9 respiratory diseases (12%), 8 born prematurely (but there was no preterm baby under 33 weeks); one infant presented a cardiac disease, and another 1 epilepsy. Five infants showed no fever, 73% had cough, and 24% had gastro-intestinal symptoms. Infants under 3 months of age presented less cough (P<0.025) and fewer gastro-intestinal symptoms (P<0.01) than older ones. Only 5 infants needed oxygen and 4 presented pneumonia. Forty-eight infants were hospitalized, including 1 in intensive care, with a median duration of 3 days. Forty-five percent spent 2 days or less in the hospital. Infants under 3 months of age were more often hospitalized (P<0.001). CONCLUSIONS: Infants under 6 months of age did not present a severe form of influenza A(H1N1)v. Infants under 3 months of age were less symptomatic than older infants and were often hospitalized, but hospital stays were short with a good outcome.

Changing species distribution and antimicrobial susceptibility pattern of Shigella over a 29-year period (1980-2008).

We studied changes in species distribution and antimicrobial resistance patterns of Shigella during 1980-2008, using the Diarrhoeal Diseases Surveillance system of Dhaka Hospital of ICDDR,B. In hospitalized patients Shigella prevalence decreased steadily from 8-12% in the 1980s to 3% in 2008. Endemic S. flexneri was the most commonly isolated species (54%). Epidemic S. dysenteriae type 1 had two peaks in 1984 and 1993, but was not found after 2000, except for one case in 2004. The therapeutic options are now limited: in 2008 a total of 33% of S. flexneri were resistant to ciprofloxacin and 57% to mecillinam. In the <5 years age group, severely underweight, wasted and stunted children were more at risk of shigellosis compared to well-nourished children (P<0·001). Although hospitalization for Shigella diarrhoea is decreasing, the high levels of antimicrobial resistance and increased susceptibility of malnourished children continue to pose an ongoing risk.

Clinical characteristics of the smooth tubercle bacilli 'Mycobacterium canettii' infection suggest the existence of an environmental reservoir.

Over a 3-year follow-up, 30 out of the 318 unique Mycobacterium tuberculosis complex isolates recovered in the Republic of Djibouti had a smooth-type morphology and were Niacine-negative, the characteristics of 'Mycobacterium canettii' strains. Unlike M. tuberculosis, 'M. canettii' grew on nutrient-poor media at 30°C, and possessed characteristic lipids. They were isolated from respiratory and extra-respiratory sites from patients with typical forms of tuberculosis. Most cases resolved with antibiotic therapy but in two human immunodeficiency virus-positive patients 'M. canettii' infection led to septicaemia and death. No cases of human-to-human transmission were observed. The proportion of tuberculosis cases caused by 'M. canettii' was higher among French patients than among Djiboutian patients. Patients with 'M. canettii' were significantly younger than those with tuberculosis caused by other M. tuberculosis complex strains. Smooth tubercle bacilli could be misidentified as non-tuberculous mycobacteria and appear to be limited to the Horn of Africa. Their characteristics are consistent with the existence of non-human sources of infection.

Multilocus variable number tandem repeat analysis for Salmonella enterica subspecies.

Genomic analysis of Salmonella enterica revealed the existence of a variable number of tandem repeats (VNTR) at multiple loci. Some S. enterica strains are considered as references (Typhi Ty2, Typhi CT18, Typhimurium LT2, Enteritidis LK5, PT4, and Enteritidis 07-2642, and Newport). These allowed the selection of markers to develop the genotyping technique, multiple-locus VNTR analysis (MLVA). These markers were used to discriminate S. enterica isolated from humans, food, or the environment. In this report, the characteristics and specifications of 58 salmonella markers described from 2003 to 2009 are analyzed. Some VNTR loci were used as markers. The markers were used to discriminate S. enterica isolates from different sources and geographical localizations. Among the VNTR loci described in the published reports, eight presented with a high diversity index (DI) of polymorphism of more than 0.80. The selection of several markers within a single locus validated their polymorphism characteristic. Despite unequal DI values, the use of a panel of markers is a powerful discriminatory tool for the surveillance and identification of the source of salmonella outbreak. Depending on the markers selected, MLVA should be used either for macro- or microepidemiological purposes. The main challenge in the future for this technique is standardization.

A travel misadventure--visceral leishmaniasis in an immunocompetent patient.

Visceral leishmaniasis is one of the world's most neglected diseases. Over 90% of the 500,000 annual new cases occur in only five countries: India, Nepal, Bangladesh, Sudan and North-Eastern Brazil, but the disease remains endemic in Southern Europe. We report a case of visceral leishmaniasis in an immunocompetent serviceman after a seven-day stay in the Marseilles region of South-Eastern France. This case is intended to alert clinicians to the possibility of visceral leishmaniasis in patients who develop a febrile illness after returning from travel in Southern European countries.

[Noroviruses: leading cause of gastroenteritis]. / Les norovirus: une cause majeure des gastro-entérites.

Although noroviruses were the first viral agents to be linked to gastrointestinal disease, they were long considered a secondary cause far behind rotaviruses. Development of molecular-based diagnostic techniques has provided clearer insight into the epidemiological impact of noroviruses that are now recognized not only as the leading cause of non-bacterial gastroenteritis outbreaks but also as an important cause of sporadic gastroenteritis in both children and adults. Norovirus infection is generally characterized by mild acute vomiting and diarrhea usually lasting for only a few days, but it can lead to more severe and potentially life-threatening symptoms in high-risk groups such as young children, elderly, and immunodeficient persons. It has been demonstrated that they are present in tropical countries. Molecular epidemiological studies have documented the great genetic diversity of noroviruses with regular emergence of variants. Since no vaccine is available, prevention on norovirus infection depends mainly on strict personal and community hygiene measures.

Noroviruses: a challenge for military forces.

For military forces, the control of infectious acute gastroenteritis constitutes an old, constant and unsolved concern. Recent epidemiological studies suggest that the common bacterial causes are being overtaken by viruses. Norviruses are the most alarming group and norovirus outbreaks in military forces are regularly reported. Illness is generally mild and characterised by acute vomiting and diarrhoea, which lasts for a few days on average, but may be severe and potentially life-threatening in subjects who are already dehydrated due to daily activity. Moreover, outbreaks may diminish operational effectiveness. Prevention of norovirus infection currently relies on strict application of personal and collective hygiene rules including isolation of the cases, to the greatest possible extent. Although noroviruses are frequently mentioned as the cause of gastroenteritis outbreaks in troops deployed overseas, laboratory diagnosis is rarely done. So their real burden in military forces remains unclear and further epidemiological studies are required to determine the full impact of norovirus gastroenteritis on troops.

[Diagnosis of tuberculosis in developing countries: new perspectives]. / Diagnostic biologique de la tuberculose dans les pays à faibles ressources: perspectives nouvelles.

Tuberculosis (TB) is still a major public health problem in the world despite the ambitious goals of the DOTS strategy, i.e., detection of 70% of new cases and successfully treatment of at least 85% of those cases. One of the main reasons for this relative failure is lack of a sensitive method for reliable diagnosis particularly in HIV-positive patients. Development of new diagnostic tools is a top priority in the WHO's "Global plan to stop TB, 2006-2015". Numerous avenues of research have been proposed including development of immunological tests to detect antigens and antibodies, cutaneous tests, respiratory tests, improved solid or liquid culture techniques, alternatives to culture techniques, molecular biology techniques, etc. Some of these techniques will require long-term development and others will probably never be suitable for routine diagnosis. However a few innovations such as optimization of direct microscopic examination using new lower-priced fluorescence microscopes are ready for rapid deployment. Another promising area of research involves immunoenzymatic testing on urine samples. In any event clinical trials will be necessary to demonstrate the efficacy of these new diagnostic tools. These trials must be conducted and controlled under field conditions in the geographical zones where they will be used, i.e. in low-income countries with high incidences of TB.

[Interest of new molecular typing method in the study of hospital transmitted Staphylococcus aureus population]. / Etude des populations staphylococciques hospitalières: apport des techniques récentes de biologie moléculaire.

OBJECTIVES: To determinate the origin of acquired S. aureus among hospitalised patients and to evaluate the transmission of strains between health care workers and hopistalised patients. METHODS: The method chosen is a prospective study in risky clinical yards. Nasal swabing of patients and health care workers has been done to isolate bacterial samples. Caracterisation and comparaison of bacterial strains have been made using their antibiotic resistance profil and a recent molecular genotyping technic named MLVA (Multi Locus Variable Number of Tandem Repeat). It has never been used in such context. RESULTS: One hundred and fifty-seven strains have been isolated. They have been compared while realizing 1900 PCR and agar gel electrophoresis in 10 days. 15 clones were identified. One of them is mainly represented among patient's nasal carriage and acquired strains. As far as antibiotype and agr type are concerned, it is similar to hospital-acquired clone described in Europe with other technics (MRSA, Gentamicine-S agr 1). This clone appears to be also transmitted between health care workers and patients. CONCLUSION: Although it exists, we can't appreciate the intensity of this transmission. These results don't allow us to proceed to a systematic screening for nasal carriage among our health care workers. This study shows that MLVA could be a reliable molecular typing method, which could be used in every day practice. In our experience, it is as performing as PFGE, more didactic, faster and easier.

[Staphylococcus aureus infections carrying Panton-Valentine leukocidin genes in hospitals: which statute should be given to these strains?]. / Infections à Staphylococcus aureus porteurs du gène codant la leucocidine de Panton-Valentine à l'hôpital: quel statut donner à ces souches?

OBJECTIVES: The aim of the present study was to investigate the prevalence Staphylococcus aureus infections carrying Panton-Valentine leukocidin (LPV) genes in our hospital by screening patients that are hospitalised or admitted for consultation, as well as to study the characteristics of these strains and the respectively infected patients. METHODS: A descriptive and retrospective study over the course of a 14 month period was conducted. The isolates of S. aureus were tested for antimicrobial resistance, in which detection of the virulence gene was performed by way of PCR, such as is the case for gene luk-PV which encoding the LPV. The genetic diversity of the strains carrying gene, luk-PV, was determined by way of pulsed-field gel electrophoresis and by the MLVA (Multiple Loci VNTR Analysis; VNTR, Variable Number of Tandem Repeats) method. RESULTS: 7.14% of the S. aureus isolates carried genes for LPV, which are primarily sourced from surgery, emergency, and outpatient consultation services. The nature of the reported infections is often surface, immediately collected, and more rarely deep. Genotyping revealed three principal clones that were gathering 55% of the strains, which in turn highlighted transmission to the nursing staff. COMMENTS: These strains of S. aureus LPV+ have the capacity for diffusion and pathogenicity, which leads to the need to take some specific measures at hospitals: the tracking of the LPV during repeat or deep infections with S. aureus, possibly the search for conveyance and individual measures for the eradication of the strain. Lastly, it is necessary to increase the nursing staff's awareness of the appropriate hygiene measures when they come into contact with these patients.