Importance of antibiotic class to the development of Clostridium difficile infection (CDI) in adults: A systematic review

C. difficile causes gastrointestinal infections in humans, including severe diarrhea. It is implicated in 20%-30% of cases of antibiotic-associated diarrhea, in 50%-70% of cases of antibiotic-associated colitis, and in >90% of cases of antibiotic-associated pseudomembranous colitis. Exposure to antimicrobial agent, hospitalization and age are some of the risk factors that predispose to CDI. Virtually all hospitalized patients with nosocomially-acquired CDI have a history of treatment with antimicrobials or neoplastic agent within the previous 2 months. The development of CDI usually occurs during treatment with antibiotics or some weeks after completing the course of the antibiotics. ^ After exposure to the organism (often in a hospital), the median incubation period is less than 1 week, with a median time of onset of 2days. The difference in the time between the use of antibiotic and the development of the disease relate to the timing of exogenous acquisition of C. difficile. ^ This paper reviewed the literature for studies on different classes of antibiotics in association with the rates of primary CDI and RCDI from the year 1984 to 2012. The databases searched in this systematic review were: PubMed (National Library of Medicine) and Medline (R) (Ovid). RefWorks was used to store bibliographic data. ^ The search strategy yielded 733 studies, 692 articles from Ovid Medline (R) and 41 articles from PubMed after removing all duplicates. Only 11 studies were included as high quality studies. Out of the 11 studies reviewed, 6 studies described the development of CDI in non-CDI patients taking antibiotics for other purposes and 5 studies identified the risk factors associated with the development of recurrent CDI after exposure to antibiotics. ^ The risk of developing CDI in non-CDI patients receiving beta lactam antibiotics was 2.35%, while fluoroquinolones, clindamycin/macrolides and other antibiotics were associated with 2.64%, 2.54% and 2.35% respectively. Of those who received beta lactam antibiotic, 26.7% developed RCDI, while 36.8% of those who received any fluoroquinolone developed RCDI, 26.5% of those who received either clindamycin or macrolides developed RCDI and 29.1% of those who received other antibiotics developed RCDI. Continued use of non-C. difficile antibiotics especially fluoroquinolones was identified as an important risk factor for primary CDI and recurrent CDI. ^

Retrospective analysis of Methicillin-Resistant Staphylococcus Aureus (MRSA) skin and Soft-Tissue Infections (SSTI) in a university hospital emergency department (ED)

Study Objective: Identify the most frequent risk factors of Community Acquired-MRSA (CA-MRSA) Skin and Soft-tissue Infections (SSTIs) using a case series of patients and characterize them by age, race/ethnicity, gender, abscess location, druguse and intravenous drug-user (IVDU), underlying medical conditions, homelessness, treatment resistance, sepsis, those whose last healthcare visit was within the last 12 months, and describe the susceptibility pattern from this central Texas population that have come into the University Medical Center Brackenridge (UMCB) Emergency Department (ED). ^ Methods: This study was a retrospective case-series medical record review involving a convenience sample of patients in 2007 from an urban public hospital's ED in Texas that had a SSTI that tested positive for MRSA. All positive MRSA cultures underwent susceptibility testing to determine antibiotic resistance. The demographic and clinical variables that were independently associated with MRSA were determined by univariate and multivariate analysis using logistic regression to calculate odds ratios (OR), 95% confidence intervals, and significance (p≤ 0.05). ^ Results: In 2007, there were 857 positive MRSA cultures. The demographics were: males 60% and females 40%, with the average age of 36.2 (std. dev. =13) the study population consisted of non-Hispanic white (42%), Hispanics (38%), and non-Hispanic black (18.8%). Possible risk factors addressed included using recreational drugs (not including IVDU) (27%) homelessness (13%), diabetes status (12.6%) or having an infectious disease, and IVDU (10%). The most frequent abscess location was the leg (26.6%), followed by the arm and torso (both 13.7%). Eighty-three percent of patients had one prominent susceptibility pattern that had a susceptibility rate for the following antibiotics: trimethoprim/sulfamethoxazole (TMP-SMX) and vancomycin had 100%, gentamicin 99%, clindamycin 96%, tetracycline 96%, and erythromycin 56%. ^ Conclusion: The ED is becoming an important area for disease transmission between the sterile hospital environment and the outside environment. As always, it is important to further research in the ED in an effort to better understand MRSA transmission and antibiotic resistance, as well as to keep surveillance for the introduction of new opportunistic pathogens into the population. ^

GFP-targeting allows visualization of the apicoplast throughout the life cycle of live malaria parasites.

BACKGROUND INFORMATION The Plasmodium parasite, during its life cycle, undergoes three phases of asexual reproduction, these being repeated rounds of erythrocytic schizogony, sporogony within oocysts on the mosquito midgut wall and exo-erythrocytic schizogony within the hepatocyte. During each phase of asexual reproduction, the parasite must ensure that every new daughter cell contains an apicoplast, as this organelle cannot be formed de novo and is essential for parasite survival. To date, studies visualizing the apicoplast in live Plasmodium parasites have been restricted to the blood stages of Plasmodium falciparum. RESULTS In the present study, we have generated Plasmodium berghei parasites in which GFP (green fluorescent protein) is targeted to the apicoplast using the specific targeting sequence of ACP (acyl carrier protein), which has allowed us to visualize this organelle in live Plasmodium parasites. During each phase of asexual reproduction, the apicoplast becomes highly branched, but remains as a single organelle until the completion of nuclear division, whereupon it divides and is rapidly segregated into newly forming daughter cells. We have shown that the antimicrobial agents azithromycin, clindamycin and doxycycline block development of the apicoplast during exo-erythrocytic schizogony in vitro, leading to impaired parasite maturation. CONCLUSIONS Using a range of powerful live microscopy techniques, we show for the first time the development of a Plasmodium organelle through the entire life cycle of the parasite. Evidence is provided that interference with the development of the Plasmodium apicoplast results in the failure to produce red-blood-cell-infective merozoites.

Resistance development in community-acquired strains of methicillin-resistant Staphylococcus aureus: an in vitro study

This study compares in vitro antimicrobial resistance development between strains of Staphylococcus aureus including newly described community-acquired methicillin-resistant strains (CA-MRSA). High-level resistance developed in all strains of S. aureus after exposure to rifampicin and gentamicin and in some strains after fusidic acid exposure, independent of methicillin resistance phenotype. Resistance did not develop after exposure to clindamycin, cotrimoxazole, ciprofloxacin, linezolid, or vancomycin. These results have important implications for therapy of CA-MRSA infections. (C) 2004 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Infecções odontogénicas

Introdução: As infecções odontogénicas constituem uma das patologias mais prevalentes e o principal motivo para a procura de cuidados médico-dentários a nível mundial. Todos os Médicos Dentistas deverão mostrar-se aptos a realizar um rápido diagnóstico bem como decidir de forma eficaz, ponderada e devidamente fundamentada qual o tratamento a aplicar a cada caso tendo consciência que a progressão de uma infecção odontogénica é, muitas vezes, imprevisível e um tratamento tardio ou incorrecto poderá acarretar complicações que implicam risco de vida para o paciente ao comprometer os espaços faciais profundos da cabeça e pescoço. Objectivo: Esta dissertação pretende, recorrendo à literatura existente, auxiliar o Médico Dentista no diagnóstico de uma infecção odontogénica e, essencialmente, evidenciar qual o tratamento preconizado ou considerado mais eficaz para este tipo de infecções orais. Materiais e métodos: Para a execução desta revisão da literatura, foi desenvolvida uma pesquisa, entre Janeiro e Junho de 2016, recorrendo à Biblioteca Ricardo Reis da Universidade Fernando Pessoa e à Biblioteca da Faculdade de Medicina Dentária da Universidade do Porto, ao portal “DGS” e às bases de dados electrónicas: PUBMED, SCIENCEDIRECT e Repositório Institucional da Universidade de Barcelona utilizando, para esse fim, as “palavras-chave” estabelecidas. Em suma, na realização da presente dissertação, foram consultadas três obras literárias e 23 artigos científicos. Conclusão: Segundo a literatura analisada, não existe consenso absoluto sobre qual o antibiótico que deverá ser prescrito no tratamento de infecções odontogénicas. A amoxicilina continua a ser referenciada como primeira linha de tratamento e, a necessidade e as vantagens da associação desta ao ácido clavulânico, são evidenciadas por diversos autores. A clindamicina é o antibiótico que se apresenta como segunda linha de tratamento, em casos de alergia aos beta-lactâmicos.

The prevalence of genotypes that determine resistance to macrolides, lincosamides, and streptogramins B compared with spiramycin susceptibility among erythromycin-resistant Staphylococcus epidermidis

Coagulase-negative staphylococci, particularly Staphylococcus epidermidis , can be regarded as potential reservoirs of resistance genes for pathogenic strains, e.g., Staphylococcus aureus . The aim of this study was to assess the prevalence of different resistance phenotypes to macrolide, lincosamide, and streptogramins B (MLSB) antibiotics among erythromycin-resistant S. epidermidis, together with the evaluation of genes promoting the following different types of MLSB resistance: ermA, ermB, ermC, msrA, mphC, and linA/A’. Susceptibility to spiramycin was also examined. Among 75 erythromycin-resistant S. epidermidis isolates, the most frequent phenotypes were macrolides and streptogramins B (MSB) and constitutive MLSB (cMLSB). Moreover, all strains with the cMLSB phenotype and the majority of inducible MLSB (iMLSB) isolates were resistant to spiramycin, whereas strains with the MSB phenotype were sensitive to this antibiotic. The D-shape zone of inhibition around the clindamycin disc near the spiramycin disc was found for some spiramycin-resistant strains with the iMLSB phenotype, suggesting an induction of resistance to clindamycin by this 16-membered macrolide. The most frequently isolated gene was ermC, irrespective of the MLSB resistance phenotype, whereas the most often noted gene combination was ermC, mphC, linA/A’. The results obtained showed that the genes responsible for different mechanisms of MLSB resistance in S. epidermidis generally coexist, often without the phenotypic expression of each of them.

Utilización de antimicrobianos en las infecciones odontogénicas en niños y adolescentes: análisis farmacocinético/farmacodinámico (PK/PD)

El objetivo de este estudio es evaluar la eficacia de los tratamientos más utilizados en infecciones odontogénicas en niños y adolescentes aplicando criterios farmacocinéticos/farmacodinámicos (PK/PD). Se han simulado las curvas de concentración plasmática libre-tiempo a partir de parámetros farmacocinéticos medios de amoxicilina, amoxicilina-ácido clavulánico, cefuroxima axetilo, espiramicina, clindamicina, azitromicina y metronidazol. Para los antibióticos con actividad dependiente del tiempo, se ha calculado el tiempo durante el cual las concentraciones permanecen por encima de la concentración inhibitoria mínima (CIM90) de los microorganismos (T>CIM). Para los antimicrobianos con actividad dependiente de la concentración, se ha calculado el cociente entre el área bajo la curva y la CIM90 (ABC/CIM90). Con amoxicilina-ácido clavulánico (80 mg/kg/día) se han obtenido índices de eficacia adecuados frente a los microorganismos estudiados (T > CIM > 40%), excepto paraVeillonella spp. Clindamicina (40 mg/kg/día) también ha presentado índices PK/PD adecuados frente a la mayoría de los patógenos, excepto Lactobacillus, Actinobacillus actinomycetemcomitans, Peptostreptococcus resistente a penicilina y Eikenella corrodens. Con dosis altas de amoxicilina los resultados no han sido satisfactorios frente a varias especies bacterianas. Con azitromicina y metronidazol no se han alcanzado valores adecuados frente a la mayoría de patógenos (ABC/CIM90 < 25). En conclusión, el tratamiento empírico más adecuado en infecciones odontogénicas en niños y adolescentes es amoxicilina-ácido clavulánico en altas dosis de amoxicilina, aunque se puede utilizar como alternativa clindamicina. Sería conveniente confirmar estos resultados mediante ensayos clínicos, para cuyo diseño y evaluación podría ser de gran utilidad la aplicación de estudios PK/PD.