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Abstract The main objective of this work is to describe the formation of the Transition Adolescent Clinic (TAC) and understand the process of transitioning adolescents with HIV/AIDS from pediatric to adult care, from the vantage point of individuals subjected to this process. A qualitative method and an intentional sample selected by criteria were adopted for this investigation, which was conducted in São Paulo, Brazil. An in-depth semi-structured interview was conducted with sixteen HIV-infected adolescents who had been part of a transitioning protocol. Adolescents expressed the need for more time to become adapted in the transition process. Having grown up under the care of a team of health care providers made many participants have reluctance toward transitioning. Concerns in moving away from their pediatricians and feelings of disruption, abandonment, or rejection were mentioned. Participants also expressed confidence in the pediatric team. At the same time they showed interest in the new team and expected to have close relationships with them. They also ask to have previous contacts with the adult health care team before the transition. Their talks suggest that they require slightly more time, not the time measured in days or months, but the time measured by constitutive experiences capable of building an expectation of future. This study examines the way in which the adolescents feel, and help to transform the health care transition model used at a public university. Listening to the adolescents’ voices is crucial to a better understanding of their needs. They are those who can help the professionals reaching alternatives for a smooth and successful health care transition.

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Abstract Objective The diagnosis of extrapulmonary tuberculosis is still a challenge because of its pauci-bacillary nature. The aim of the study was to evaluate the role of a multiplex PCR assay in the diagnosis of extrapulmonary tuberculosis and to compare the efficiency of two targets, IS6110 and MPB64 to detect Mycobacterium tuberculosis. Methods 150 extrapulmonary samples (61 pus/aspirate, 46 tissue, 32 body fluids, and 11 urine) from clinically suspected cases of tuberculosis were included in the study. All the samples were subjected to direct fluorescent microscopy, TB culture (BacT/ALERT 3D, biomerieux, Durham, North Carolina, USA) and a Multiplexed Tandem PCR targeting two mycobacterial DNA sequences, IS6110 and MPB64. Master-Mix reagents and primers were prepared by AusDiagnostics Pvt. Ltd (Alexandria, New South Wales, Australia). The performance of the assay was assessed using a composite gold standard, which included clinical characteristics, microbiology smear as well as culture, histopathology, cytology, radiology, and response to antitubercular therapy. Results 20.3%, 23.6%, and 45.3% of specimens were positive by smear, culture, and PCR, respectively. The sensitivity and specificity of the multiplex PCR was 91.9% and 88.4%, respectively, using the composite gold standard. Positive and negative predictive values of the PCR were estimated as 85.1% and 93.8%, respectively. Higher positivity was observed with target IS6110 (44.6%) as compared to target MPB64 (18.9%). The sensitivities of IS6110 and MPB64 individual targets were 90.3% and 64.5%, respectively, and specificities were 88.4% and 97.7%, respectively. Conclusion PCR can play an important role in rapid and accurate diagnosis of extrapulmonary tuberculosis. IS6110 alone is an effective target in our part of the country.

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Abstract Introduction Infections caused by Streptococcus pneumoniae (pneumococcus) still represent a challenge for health systems around the world. Objective The objective of this study was to assess microbiological and clinical aspects in hospitalized patients with invasive pneumococcus disease between 1998 and 2013. Materials and methods This was a retrospective study that analyzed the results of pneumococcus identification, serotyping, and susceptibility testing found in the Adolfo Lutz Institute databank. Personal variables, medical history and clinical outcome of patients admitted with invasive pneumococcal disease were analyzed. These were obtained from records of a public teaching hospital – Hospital das Clínicas Faculdade de Medicina Ribeirão Preto. Results The sample comprised 332 patients. Patient age ranged from less than one month to 89 years old (mean 20.3 years) and the sample was predominately male. Pneumonia (67.8%) was the most common disease, accounting for 18.2% of deaths. Serotypes 14, 1, 3, 9V, 6B, 6A, 23F, 19A, 18C, 19F, 12F, and 4 were the most common (75.3%). Most patients, or 67.5%, were cured without any complication (success), 6.9% had some type of sequela (failure), and 25.6% died (failure). In the case of deaths due to meningitis, strains of fully penicillin resistant pneumococcus were isolated. Furthermore, 68.2% of patients who died presented some type of comorbidity. The 60 and older age group presented the most significant association (Odds Ratio = 4.2), with outcome failure regardless of the presence of comorbidity. Serotype 18C was the most significant risk factor both in raw analysis (Odds Ratio = 3.8) and when adjusted for comorbidity (Odds Ratio = 5.0) or age (Odds Ratio = 5.4). The same occurred with serotype 12F (respectively, Odds Ratio = 5.1, Odds Ratio = 5.0, and Odds Ratio = 4.7) Conclusion The present findings highlight the importance of IPD among young adults and older adults. In the era of conjugate vaccines, monitoring serotypes in different age groups is essential to assess the impact and adequacy of immunization.

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Abstract Aim The aim of this study was to compare both the efficacy and safety profile of the WHO-recommended, dual therapy (doxycycline–rifampin) to a quinolone-based, triple therapy (doxycycline–rifampin–levofloxacin) for treating acute/subacute brucellosis. Patients and methods We studied 107 consecutive, naïve patients with acute/subacute brucellosis admitted to Assiut University Hospital. Patients were randomly allocated to receive the dual therapy of doxycycline–rifampin (group-A) or to receive the triple therapy of doxycycline–rifampin–levofloxacin (group-B). Acute/subacute brucellosis was diagnosed based on the presence of: (1) contact with animals or fresh animal products, (2) suggestive clinical manifestations of less than one-year duration, and (3) positive antibody titer (1:160) by standard tube agglutination test. Results There was no significant difference between the two groups regarding their demographic data. Fever was the most frequent manifestation (96.3%). Epigastric pain was the most frequent adverse effect of treatment (12.1%). Group-A patients had a significantly higher relapse rate compared to group-B patients (22.6% versus 9.3%, p-value = 0.01). The rate of treatment adverse effects was higher among group-B patients, although not reaching statistical significance (20.4% versus 11.3%, p-value = 0.059). Conclusions Adding levofloxacin to the dual therapy for acute/subacute brucellosis (doxycycline–rifampin) may increase its efficacy in terms of lowering the relapse rate of the disease. Further, larger scale studies are needed before considering modifying the standard, dual therapy for brucellosis.

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Abstract There is a lack of formal economic analysis to assess the efficiency of antimicrobial stewardship programs. Herein, we conducted a cost-effectiveness study to assess two different strategies of Antimicrobial Stewardship Programs. A 30-day Markov model was developed to analyze how cost-effective was a Bundled Antimicrobial Stewardship implemented in a university hospital in Brazil. Clinical data derived from a historical cohort that compared two different strategies of antimicrobial stewardship programs and had 30-day mortality as main outcome. Selected costs included: workload, cost of defined daily doses, length of stay, laboratory and imaging resources used to diagnose infections. Data were analyzed by deterministic and probabilistic sensitivity analysis to assess model's robustness, tornado diagram and Cost-Effectiveness Acceptability Curve. Bundled Strategy was more expensive (Cost difference US$ 2119.70), however, it was more efficient (US$ 27,549.15 vs 29,011.46). Deterministic and probabilistic sensitivity analysis suggested that critical variables did not alter final Incremental Cost-Effectiveness Ratio. Bundled Strategy had higher probabilities of being cost-effective, which was endorsed by cost-effectiveness acceptability curve. As health systems claim for efficient technologies, this study conclude that Bundled Antimicrobial Stewardship Program was more cost-effective, which means that stewardship strategies with such characteristics would be of special interest in a societal and clinical perspective.

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Abstract Background Hepatitis E virus (HEV) can cause chronic infection with rapid progression to liver cirrhosis in immunocompromised patients. HEV seroprevalence in patients with Schistosoma mansoni in Brazil is unknown. We evaluated the prevalence of past or present HEV infection in schistosomiasis patients in Recife, Pernambuco, Brazil. A total of 80 patients with Schistosoma mansoni were consecutively enrolled in a cross-sectional study. Serum samples were tested for the presence of anti-HEV IgG antibodies by enzyme immunoassay (Wantai anti-HEV IgG, Beijing, China) and for the presence of HEV RNA using real time reverse transcriptase-polymerase chain reaction with primers targeting the HEV ORF2 and ORF3. Clinical and laboratory tests as well as abdominal ultrasound were performed at the same day of blood collection. Results Anti-HEV IgG was positive in 18.8% (15/80) of patients with SM. None of the samples tested positive for anti-HEV IgM or HEV-RNA. Patients with anti-HEV IgG positive presented higher levels of alanine aminotranferase (p = 0.048) and gama-glutamil transferase (p = 0.022) when compared to patients without anti-HEV IgG antibodies. Conclusion This study demonstrates that the seroprevalence of HEV is high in patients with Schistosoma mansoni in Northeastern of Brazil. Past HEV infection is associated with higher frequency of liver enzymes abnormalities. HEV infection and its role on the severity of liver disease should be further investigated among patients with Schistosoma mansoni.

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Abstract Objectives The aim of this study was to evaluate the impact of a bundle called FAST HUG in ventilator-associated pneumonia, weigh the healthcare costs of ventilator-associated pneumonia patients in the intensive care unit, and hospital mortality due to ventilator-associated pneumonia. Material and methods The study was performed in a private hospital that has an 8-bed intensive care unit. It was divided into two phases: before implementing FAST HUG, from August 2011 to August 2012 and after the implementation of FAST HUG, from September 2012 to December 2013. An individual form for each patient in the study was filled out by using information taken electronically from the hospital medical records. The following data was obtained from each patient: age, gender, reason for hospitalization, use of three or more antibiotics, length of stay, intubation time, and outcome. Results After the implementation of FAST HUG, there was an observable decrease in the occurrence of ventilator-associated pneumonia (p < 0.01), as well as a reduction in mortality rates (p < 0.01). In addition, the intervention resulted in a significant reduction in intensive care unit hospital costs (p < 0.05). Conclusion The implementation of FAST HUG reduced the number of ventilator-associated pneumonia cases. Thus, decreasing costs, reducing mortality rates and length of stay, which therefore resulted in an improvement to the overall quality of care.

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Abstract Treatment of orthopedic infections usually requires prolonged antimicrobial therapy, ranging from 14 days up to 6 months. Nowadays, rising levels of antimicrobial resistance demands parenteral therapy for many patients. Outpatient parenteral antimicrobial therapy (OPAT) is a modality that allows treatment out of hospital in these situations. In Brazil, where a public universal healthcare system allows full coverage for all citizens, implantation and dissemination of OPAT programs would be beneficial for patients and for the system, because it would allow a better allocation of health resources. The Instituto de Ortopedia e Traumatologia do Hospital das Clínicas da Faculdade de Medicina da USP (IOT) started, in July 2013, a partnership with municipal health authorities in Sao Paulo, Brazil, in order to initiate an OPAT program in which patients discharged from that hospital would be able to continue antimicrobial therapy at primary care facilities. When necessary, patients could also receive their therapy at the day-hospital located at IOT. Primary care nursing and physician staff were trained about antimicrobial infusion and peripherally inserted central catheter manipulation. An OPAT specific antimicrobial protocol was designed and a special reference and counter-reference organized. As a result, 450 primary healthcare professionals were trained. In the first year of this program, 116 patients were discharged for OPAT. Chronic and acute osteomyelitis were most frequent diagnosis. Teicoplanin, ertapenem and tigecycline were the most used drugs. Duration of treatment varied from 10 to 180 days (average 101, median 42). Total sum of days in OPAT regimen was 11,698. Only 3 patients presented adverse effects. Partnership between services of different levels of complexity allowed implantation of a safe and effective public healthcare OPAT program for treatment of orthopedic infections. This program can serve as a model for developing similar strategies in other regions of Brazil and Latin America.

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Abstract Introduction There is a mechanism of macrolide resistance in Staphylococcus spp. which also affects the lincosamides and type B streptogramins characterizing the so-called MLSB resistance, whose expression can be constitutive (cMLSB) or inducible (iMLSB) and is encoded mainly by ermA and ermC genes. The cMLSB resistance is easily detected by susceptibility testing used in the laboratory routine, but iMLSB resistance is not. Therapy with clindamycin in cases of infection with isolated iMLSB resistance may fail. Objective To characterize the phenotypic (occurrence of cMLSB and iMLSB phenotypes) and molecular (occurrence of ermA and ermC genes) profiles of MLSB resistance of clinical isolates of susceptible and methicillin-resistant Staphylococcus aureus and CNS (coagulase-negative Staphylococcus) from patients of a university hospital, in Pernambuco. Methods The antimicrobial susceptibility of 103 isolates was determined by the disk diffusion technique in Mueller–Hinton agar followed by oxacillin screening. The iMLSB phenotype was detected by D test. Isolates with cMLSB and iMLSB phenotypes were subjected to polymerase chain reaction (PCR) for the detection of ermA and ermC genes. Results The cMLSB and iMLSB phenotypes were respectively identified in 39 (37.9%) and five (4.9%) isolates. The iMLSB phenotype was found only in four (10.8%) methicillin-susceptible S. aureus and one (4.5%) methicillin-resistant S. aureus. In the 44 isolates subjected to PCR, four (9.1%) only ermA gene was detected, a lower frequency when compared to only ermC 17 (38.6%) gene and to one (2.3%) isolate presenting both genes. Conclusion In the Staphylococcus spp. analyzed, the ermC gene was found more often than the ermA, although the iMLSB phenotype had been less frequent than the cMLSB. It was important to perform the D test for its detection to guide therapeutic approaches.

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Abstract In November of 2015, the Ministry of Health of Brazil published an announcement confirming the relationship between Zika virus and the microcephaly outbreak in the Northeast, suggesting that infected pregnant women might have transmitted the virus to their fetuses. The objectives of this study were to conduct a literature review about Zika virus infection and microcephaly, evaluate national and international epidemiological data, as well as the current recommendations for the health teams. Zika virus is an arbovirus, whose main vector is the Aedes sp. The main symptoms of the infection are maculopapular rash, fever, non-purulent conjunctivitis, and arthralgia. Transmission of this pathogen occurs mainly by mosquito bite, but there are also reports via the placenta. Microcephaly is defined as a measure of occipto-frontal circumference being more than two standard deviations below the mean for age and gender. The presence of microcephaly demands evaluation of the patient, in order to diagnose the etiology. Health authorities issued protocols, reports and notes concerning the management of microcephaly caused by Zika virus, but there is still controversy about managing the cases. The Ministry of Health advises notifying any suspected or confirmed cases of children with microcephaly related to the pathogen, which is confirmed by a positive specific laboratory test for the virus. The first choice for imaging exam in children with this malformation is transfontanellar ultrasound. The most effective way to control this outbreak of microcephaly probably caused by this virus is to combat the vector. Since there is still uncertainty about the period of vulnerability of transmission via placenta, the use of repellents is crucial throughout pregnancy. More investigations studying the consequences of this viral infection on the body of newborns and in their development are required.

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Abstract Tuberculosis (TB) is still considered a major global public health problem in the world and there is a concern about the worldwide increase of drug-resistance (DR). This paper describes the analysis of three Mycobacterium tuberculosis isolates from a single patient collected over a long treatment period of time. DR was initially investigated through phenotypic testing, followed by line probe assays (LPAs) and whole genome sequencing (WGS). It presents an intriguing situation where a multidrug-resistant (MDR-) TB case was diagnosed and treated based only on late phenotypic drug susceptibility testing of isolate 1. During the treatment, another two isolates were cultivated: isolate 2, nine months after starting MDR-TB treatment; and isolate 3, cultivated five months later, during regular use of anti-TB drugs. These two isolates were evaluated using molecular LPA and WGS, retrospectively. All mutations detected by LPA were also detected in the WGS, including conversion from fluoroquinolones susceptibility to resistance from isolate 2 to isolate 3. WGS showed additional mutations, including some which may confer resistance to other drugs not tested (terizidone/cycloserine) and mutations with no correspondent resistance in drug susceptibility testing (streptomycin and second-line injectable drugs).

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Abstract The purpose of this study was to assess the risk of abnormal anal cytology in women with known genital squamous intraepithelial lesion. This study evaluated 200 women with and without genital squamous intraepithelial lesion who were recruited for anal Pap smears. Women who had abnormal results on equally or over atypical squamous cells of undetermined significance were classified as having abnormal anal cytology. A multiple logistic regression analysis (stepwise) was performed to identify the risk for developing abnormal anal cytology. Data were analyzed using the SPSS 20.0 program. The average age was 41.09 (±12.64). Of the total participants, 75.5% did not practice anal sex, 91% did not have HPV-infected partners, 92% did not have any anal pathology, and 68.5% did not have anal bleeding. More than half (57.5%) had genital SIL and a significant number developed abnormal anal cytology: 13% in the total sample and 17.4% in women with genital SIL. A significant association was observed between genital squamous intraepithelial lesion and anal squamous intraepithelial lesion (PR = 2.46; p = 0.03). In the logistic regression model, women having genital intraepithelial lesion were more likely to have abnormal anal Pap smear (aPR = 2.81; p = 0.02). This report shows that women with genital squamous intraepithelial lesion must be more closely screened for anal cancer.

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Abstract Culture supernatant of sepsis-associated Escherichia coli (SEPEC) isolated from patients with sepsis caused loss of intercellular junctions and elongation of human umbilical vein endothelial cells (HUVEC). The cytotoxic factor was purified from culture supernatant of SEPEC 15 (serogroup O153) by liquid chromatography process. PAGE (polyacrylamide gel electrophoresis) showed that the purified SEPEC cytotoxic factor had a molecular mass of ∼150 kDa and consisted of at least two subunits. At the concentration of 1 CD50 (40 μg/mL) did facilitate transcytosis through the HUVEC cells monolayer of SEPEC 15 as much as E. coli K12 within 30 min without affecting cell viability. These results suggest that this cytotoxic factor, named as SPF (SEPEC's permeabilizing factor), may be an important SEPEC virulence factor that facilitates bacterial access to the bloodstream.

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Abstract Tinea capitis is generally considered as the most frequent fungal infection in childhood, as it accounts for approximately 92% of all mycosis in children. The epidemiology of this disease varies widely ranging from antropophillic, zoophilic, and geophillic dermatophytes, as the main causative agent in different geographic areas, depending on several additional factors. Nowadays, the etiology is considered to vary with age, as well with gender, and general health condition. The former reported extraordinary Tinea capitis case reports have been replaced by original articles and researches dealing with progressively changing patterns in etiology and clinical manifestation of the disease. This fact is indicative that under the umbrella of the well-known disease there are facts still hidden for future revelations. Herein, we present two rare cases of Tinea capitis in children, which totally differ from the recently established pattern, in their clinical presentation, as well as in the etiological aspect, as we discuss this potential new etiological pattern of the disease, focusing on our retrospective and clinical observation. Collected data suggest that pathogenic molds should be considered as a potential source of infection in some geographic regions, which require total rationalization of the former therapeutic conception, regarding the molds’ higher antimitotic resistance compared to dermatophytes. Molds-induced Tinea capitis should be also considered in clinically resistant and atypical cases, with further investigations of the antifungal susceptibility of the newest pathogens in the frame of the old disease. Further investigations are still needed to confirm or reject this proposal.