Polymicrobial Ventilator-Associated Pneumonia: Fighting In Vitro Candida albicans-Pseudomonas aeruginosa Biofilms with Antifungal-Antibacterial Combination Therapy.

The polymicrobial nature of ventilator-associated pneumonia (VAP) is now evident, with mixed bacterial-fungal biofilms colonizing the VAP endotracheal tube (ETT) surface. The microbial interplay within this infection may contribute for enhanced pathogenesis and exert impact towards antimicrobial therapy. Consequently, the high mortality/morbidity rates associated to VAP and the worldwide increase in antibiotic resistance has promoted the search for novel therapeutic strategies to fight VAP polymicrobial infections. Under this scope, this work aimed to assess the activity of mono- vs combinational antimicrobial therapy using one antibiotic (Polymyxin B; PolyB) and one antifungal (Amphotericin B; AmB) agent against polymicrobial biofilms of Pseudomonas aeruginosa and Candida albicans. The action of isolated antimicrobials was firstly evaluated in single- and polymicrobial cultures, with AmB being more effective against C. albicans and PolyB against P. aeruginosa. Mixed planktonic cultures required equal or higher antimicrobial concentrations. In biofilms, only PolyB at relatively high concentrations could reduce P. aeruginosa in both monospecies and polymicrobial populations, with C. albicans displaying only punctual disturbances. PolyB and AmB exhibited a synergistic effect against P. aeruginosa and C. albicans mixed planktonic cultures, but only high doses (256 mg L-1) of PolyB were able to eradicate polymicrobial biofilms, with P. aeruginosa showing loss of cultivability (but not viability) at 2 h post-treatment, whilst C. albicans only started to be inhibited after 14 h. In conclusion, combination therapy involving an antibiotic and an antifungal agent holds an attractive therapeutic option to treat severe bacterial-fungal polymicrobial infections. Nevertheless, optimization of antimicrobial doses and further clinical pharmacokinetics/pharmacodynamics and toxicodynamics studies underpinning the optimal use of these drugs are urgently required to improve therapy effectiveness and avoid reinfection.

Human papillomavirus status and cervical abnormalities in women from public and private health care in Rio de Janeiro State, Brazil.

This article reports the HPV status and cervical cytological abnormalities in patients attended at public and private gynecological services from Rio de Janeiro State. It also comments the performance of each HPV DNA tests used. A set of 454 women from private health clinics was tested by routine Capture Hybrid II HPV DNA assay. Among these, 58.4% presented HPV and nearly 90% of them were infected by high risk HPV types. However, this group presented few premalignant cervical lesions and no invasive cervical cancer was registered. We also studied 220 women from low income class attended at public health system. They were HPV tested by polymerase chain reaction using My09/11 primers followed by HPV typing with E6 specific primers. The overall HPV prevalence was 77.3%. They also showed a high percentage of high squamous intraepithelial lesion-HSIL (26.3%), and invasive cervical carcinoma (16.3%). HPV infection was found in 93.1% and 94.4% of them, respectively. The mean ages in both groups were 31.5 and 38 years, respectively. In series 1, HPV prevalence declined with age, data consistent with viral transient infection. In series 2, HPV prevalence did not decline, independent of age interval, supporting not only the idea of viral persistence into this group, but also regional epidemiological variations in the same geographic area. Significant cytological differences were seen between both groups. Normal and benign cases were the most prevalent cytological findings in series 1 while pre-malignant lesions were the most common diagnosis in the series 2. HPV prevalence in normal cases were statistically higher than those from series 1 (p<0.001), indicating a higher exposure to HPV infection. Women from both samples were referred for previous abnormal cytology. However, socio-demographic evidence shows that women from series 1 have access to treatment more easily and faster than women from series 2 before the development of pre-malignant lesions. These data provides baseline support for the role of social inequalities linked to high risk HPV infection leading to cervical cancer. Broadly screening programs and the development of safe and effective vaccines against HPV would diminish the toll of this disease that affect mainly poor women.

Human papillomavirus status and cervical abnormalities in women from public and private health care in Rio de Janeiro State, Brazil / Papilomavírus humano e anormalidades cervicais em mulheres do sistema de saúde privado e público no Estado do Rio de Janeiro, Brasil

This article reports the HPV status and cervical cytological abnormalities in patients attended at public and private gynecological services from Rio de Janeiro State. It also comments the performance of each HPV DNA tests used. A set of 454 women from private health clinics was tested by routine Capture Hybrid II HPV DNA assay. Among these, 58.4 percent presented HPV and nearly 90 percent of them were infected by high risk HPV types. However, this group presented few premalignant cervical lesions and no invasive cervical cancer was registered. We also studied 220 women from low income class attended at public health system. They were HPV tested by polymerase chain reaction using My09/11 primers followed by HPV typing with E6 specific primers. The overall HPV prevalence was 77.3 percent. They also showed a high percentage of high squamous intraepithelial lesion-HSIL (26.3 percent), and invasive cervical carcinoma (16.3 percent). HPV infection was found in 93.1 percent and 94.4 percent of them, respectively. The mean ages in both groups were 31.5 and 38 years, respectively. In series 1, HPV prevalence declined with age, data consistent with viral transient infection. In series 2, HPV prevalence did not decline, independent of age interval, supporting not only the idea of viral persistence into this group, but also regional epidemiological variations in the same geographic area. Significant cytological differences were seen between both groups. Normal and benign cases were the most prevalent cytological findings in series 1 while pre-malignant lesions were the most common diagnosis in the series 2. HPV prevalence in normal cases were statistically higher than those from series 1 (p < 0.001), indicating a higher exposure to HPV infection. Women from both samples were referred for previous abnormal cytology. However, socio-demographic evidence shows that women from series 1 have access to treatment more easily and faster than women from series 2 before the development of pre-malignant lesions...

Este artigo analisa a infecção por HPV e anormalidades citológicas cervicais encontradas em pacientes atendidas em serviços ginecológicos dos sistemas de saúde público e privado do estado do Rio de Janeiro. O trabalho também avalia os testes utilizados para detecção de DNA do HPV em cada população estudada. Um grupo de 454 mulheres oriundas de serviços da rede privada de saúde foi testado por Captura do Híbrido II. Destas, 58,4 por cento apresentaram infecção por HPV e cerca de 90 por cento delas estavam infectadas por HPV de alto risco. Este grupo, entretanto, apresentava poucos casos de lesões cervicais pré-malígnas e nenhum caso de câncer. Estudamos, também, 220 mulheres de baixo nível econômico atendidas no serviço de saúde pública que foram testadas para HPV pela reação da polimerase em cadeia utilizando-se os oligonucleotídeos My09/My11. A identificação dos tipos foi efetuada por amplificação com oligonucleotídeos específicos para a região E6 do genoma viral. A prevalência de HPV nesta população foi de 77.3 por cento, observando-se uma alta porcentagem de casos de neoplasias intraepiteliais cervicais de alto grau (26,3 por cento) e de carcinoma cervical invasivo (16,3 por cento). A infecção por HPV foi achada em, respectivamente, 93,1 por cento e 94,4 por cento destes casos. A média de idade em ambos os grupos era de 31,5 e 38 anos, respectivamente. Na série 1, a prevalência da infecção por HPV decresce com a idade, enquanto na série 2 ela não desaparece, dando suporte não só à idéia de persistência viral neste grupo, mas também a variações epidemiológicas na mesma área geográfica. Diferenças significativas foram vistas nos dois grupos. Casos normais e benignos foram incidentes na série 1, enquanto as lesões malígnas predominaram na série 2. Ao contrário, casos normais infectados por HPV eram prevalentes na série 2 (p < 0.001), indicando maior exposição ao vírus. Embora as mulheres de ambos os grupos tenham sido incluídas no estudo por apresentarem citologia anormal, evidências sócio-demográficas demonstram que mulheres da série 1 tem acesso mais fácil e rápido ao tratamento do que as mulheres da série 2 antes que as lesões pré-malígnas se desenvolvam...