Very early prediction of response to HCV treatment with PEG-IFN-alfa-2a and ribavirin in HIV/HCV-coinfected patients.

The objective of this study was to find very early viral kinetic markers to predict nonresponse to hepatitis C virus (HCV) therapy in a group of human immunodeficiency virus (HIV)/HCV-coinfected patients. Twenty-six patients (15 HCV genotype-1 and 11 genotype-3) were treated with a 48-week regimen of peginterferon-alfa-2a (PEG-IFN) (180 µg/week) and weight-based ribavirin (11 mg/kg/day). Samples were collected at baseline; 4, 8, 12, 18, 24, 30, 36 and 42 h; days 2, 3, 4, 7, 8, 15, 22, 29, 43 and 57 then weekly and monthly. Five patients discontinued treatment. Seven patients (27%) achieved a sustained virological response (SVR). Nadir HCV RNA levels were observed 1.6 ± 0.3 days after initiation of therapy, followed by a 0.3- to 12.9-fold viral rebound until the administration of the second dose of PEG-IFN, which were not associated with SVR or HCV genotype. A viral decline <1.19 log for genotype-1 and <0.97 log for genotype-3, 2 days after starting therapy, had a negative predictive value (NPV) of 100% for SVR. The day 2 virological response had a similar positive predictive value for SVR as a rapid virological response at week 4. In addition, a second-phase viral decline slope (i.e., measured from day 2 to 29) <0.3 log/week had a NPV = 100% for SVR. We conclude that first-phase viral decline at day 2 and second-phase viral decline slope (<0.3 log/week) are excellent predictors of nonresponse. Further studies are needed to validate these viral kinetic parameters as early on-treatment prognosticators of nonresponse in patients with HCV and HIV.

Tissue and serum immune response in chronic hepatitis C with mild histological lesions.

The immunopathogenesis of chronic hepatitis C virus (HCV) infection is a matter of great controversy and has been suggested to involve a complex balance between cytokines with pro and anti-inflammatory activity. We investigated the expression of inflammatory cells and cytokines in the liver and serum of 51 chronically HCV infected patients and compared them to data from two sets of normal controls: 51 healthy blood donors and 33 liver biopsies of healthy liver donors. We also assessed the relationship between selected cytokines and cell populations in hepatic compartments and the disease stage. Compared with controls, hepatitis C patients had a greater expression of portal TNF-alpha, TGF-beta and CD4(+) and acinar IFN-gamma, TNF-alpha, IL-1beta and IL-4, as well as a higher serum concentration of IL-2, IL-10 and TGF-beta. Significant positive correlations were found between portal CD4+ and TNF-alpha, portal CD8(+) and TGF-beta, portal CD45(+)RO and TNF-alpha, acinar CD45(+)RO and IFN-gamma and acinar CD57(+) and TGF-beta. In conclusion, we have shown that (i) in this sample of predominantly mild disease, the immune response was associated with a pro-inflammatory response pattern, (ii) CD4(+) T-lymphocytes played a major role in orchestrating the immune response and (iii) these events primarily took place in the portal space.

Reconstruction of full thickness scalp defects after tumour excision in elderly patients: our experience with Integra dermal regeneration template.

BACKGROUND: Scalp reconstruction after wide tumor excision is particularly challenging. Free tissue transfers, local flaps, or skin grafts can be used but present some disadvantages especially with old patients with local advanced cancers, systemic diseases and in patients with a prior history of recurring scalp skin cancers in which the risk of burying a recurring tumor with a flap is likely. The Authors expose their early experience with Integra dermal regeneration template for scalp reconstruction after scalp tumor excision. METHODS: Eight patients with primary or secondary scalp tumor underwent a first surgical procedure under local anaesthesia for tumor removal and Integra positioning followed by a second operation performed three weeks later to reconstruct the defect by removing the superficial silicon layer of Integra and by covering the defect with a split thickness skin graft. The average surface area of the defect was 143.27 cm(2). The average operating time was 30.4 minutes for the first operation and 45.6 minutes for the second operation. In six cases Integra was grafted as a classic full-thickness skin graft. In the remaining two cases the Integra template was meshed. The artificial derma was attached to the edge of the wound by either sutures or staples. RESULTS: There was a full graft take on all cases. The mean follow-up was 24 months. In two cases we were able to detect early tumor recurrence two months after the operation. Satisfactory cosmetic and functional results were obtained in all patients. CONCLUSIONS: In the scalp defect reconstructions after tumor excision, Integra allows to obtain a thicker and more durable coverage than skin graft on the skull, allowing to detect a tumor recurrence earlier than a flap reconstruction with no risk of burying an eventual underlying residual tumor. These operations are performed under local anaesthesia and are therefore suitable for elderly patients.

Genotypic distribution of hepatitis C among hepatitis C and HIV co-infected patients in Brazil.

Information on hepatitis C virus (HCV) genotypic distribution among HIV-HCV co-infected patients is lacking in Brazil as well as other Latin American countries. The objective of this study was to evaluate the level of exposure to different risk factors associated with HCV transmission among a group of co-infected patients and to characterize the genotypic distribution of HCV in this cluster. A series of 100 HIV-HCV co-infected patients was analysed. The data to be analysed were collected from specific laboratory tests. Information was collected through a questionnaire. HCV genotyping was carried out by sequencing the 5' non-coding region of HCV. Chi-square and Fischer association tests or Kruskal-Wallis test were used to study the association between HCV transmission-related variables and the established genotypes. In conclusion, exposure to multiple risk factors associated with HCV transmission was common among HIV co-infected patients and an association between HCV genotype 3 and intravenous drug user was observed.

Factors associated with mortality in patients with bloodstream infection and pneumonia due to Stenotrophomonas maltophilia.

Severe infections caused by Stenotrophomonas maltophilia are associated with high mortality, and strategies to improve the clinical outcome for infected patients are needed. A retrospective cohort study of patients with bloodstream infection (BSIs) and pneumonia caused by S. maltophilia was conducted. Multivariate analysis was performed to access factors associated with 14-day mortality. A total of 60 infections were identified. Among these, eight (13%) were pneumonias and 52 were BSIs; 33.3% were primary, 13% were central venous catheter (CVC)-related and 40% were secondary BSIs. Fifty-seven (85%) patients had received previous antimicrobial therapy; 88% had CVC, 57% mechanical ventilation and 75% were in the intensive care unit at the onset of infection. Malignancy (45%) was the most frequent underlying disease. The mean of the Acute Physiology and Chronic Health Evaluation II (APACHE II) scores was 17 and for the Sepsis-related Organ Failure Assessment (SOFA) score, it was 7 points. The overall and 14-day mortality were, respectively, 75% and 48%. Forty-seven (78%) patients were treated and, of these, 74% received trimethoprim-sulfamethoxazole. Independent risk factors associated with mortality were SOFA index >6 points (0.005) and septic shock (0.03). The Kaplan-Meier estimations curves showed that patients with APACHE II score >20 and SOFA score >10 had a survival chance of, respectively, less than 8% and less than 10% (P

Clinical classification of tetanus patients.

The authors propose a clinical classification to monitor the evolution of tetanus patients, ranging from grade I to IV according to severity. It was applied on admission and repeated on alternate days up to the 10th day to patients aged > or = 12 years admitted to the State University Hospital, Recife, Brazil. Patients were also classified upon admission according to three prognostic indicators to determine if the proposed classification is in agreement with the traditionally used indicators. Upon admission, the distribution of the 64 patients among the different levels of the proposed classification was similar for the groups of better and worse prognosis according to the three indicators (P > 0.05), most of the patients belonging to grades I and II of the proposed classification. In the later reclassifications, severe forms of tetanus (grades III and IV) were more frequent in the categories of worse prognosis and these differences were statistically significant. There was a reduction in the proportion of mild forms (grades I and II) of tetanus with time for the categories of worse prognostic indicators (chi-square for trend: P = 0.00006, 0.03, and 0.00000) whereas no such trend was observed for the categories of better prognosis (grades I and II). This serially used classification reflected the prognosis of the traditional indicators and permitted the comparison of the dynamics of the disease in different groups. Thus, it becomes a useful tool for monitoring patients by determining clinical category changes with time, and for assessing responses to different therapeutic measures.

Clinical classification of tetanus patients

The authors propose a clinical classification to monitor the evolution of tetanus patients, ranging from grade I to IV according to severity. It was applied on admission and repeated on alternate days up to the 10th day to patients aged > or = 12 years admitted to the State University Hospital, Recife, Brazil. Patients were also classified upon admission according to three prognostic indicators to determine if the proposed classification is in agreement with the traditionally used indicators. Upon admission, the distribution of the 64 patients among the different levels of the proposed classification was similar for the groups of better and worse prognosis according to the three indicators (P > 0.05), most of the patients belonging to grades I and II of the proposed classification. In the later reclassifications, severe forms of tetanus (grades III and IV) were more frequent in the categories of worse prognosis and these differences were statistically significant. There was a reduction in the proportion of mild forms (grades I and II) of tetanus with time for the categories of worse prognostic indicators (chi-square for trend: P = 0.00006, 0.03, and 0.00000) whereas no such trend was observed for the categories of better prognosis (grades I and II). This serially used classification reflected the prognosis of the traditional indicators and permitted the comparison of the dynamics of the disease in different groups. Thus, it becomes a useful tool for monitoring patients by determining clinical category changes with time, and for assessing responses to different therapeutic measures.

Investigation of the possible association between nosocomial candiduria and candidaemia.

This study aimed to determine whether candiduria is associated with the occurrence of nosocomial candidaemia. In the case-control part of the study, 115 cases (nosocomial candidaemia) and 115 controls (nosocomial bacteraemia) were similar in age, severity of condition and time of hospitalisation. There was a significant association of candidaemia with candiduria (OR 9.79; 95% CI 2.14-44.76). In the microbiology part of the study, 23 pairs of Candida-positive urine and blood cultures were obtained from 23 patients. In ten (43%) cases, the urine and blood culture isolates belonged to different species, and molecular typing showed a difference in two of the 13 cases yielding the same species from both specimens. Overall, there was a significant association between candiduria and candidaemia, but the Candida isolates from urine and blood were different for 52% of the patients. Thus, the data indicated that the urinary tract was probably not a source for the candidaemia.

Factors associated with penicillin-nonsusceptible pneumococcal infections in Brazil.

Resistance of Streptococcus pneumoniae is a worldwide, growing problem. Studies of factors associated with resistance to penicillin have not been conducted in Brazil. The objective of the present study was to evaluate factors associated with infection by S. pneumoniae not susceptible to penicillin. A prevalence study was conducted including all patients with a positive culture for S. pneumoniae in a hospital from July 1991 to December 1992 and the year 1994. Of 165 patients identified, 139 were considered to have clinically relevant infections and 88% of them had invasive infections. All infections were community acquired and consisted of pneumonia (44%) and of central nervous system (19%), pelvic or abdominal (12%), upper airway or ocular (12%), primary bloodstream (9%) and skin and soft tissue (5%) infections. Mortality was 25%. Susceptibility to penicillin was present in 77.6% of the isolates; 21.8% were relatively resistant, and one isolate was resistant (minimal inhibitory concentration = 4 micro g/ml). Multivariate analysis showed that age below 4 years (odds ratio (OR): 3.53, 95% confidence interval (95%CI): 1.39-8.96) and renal failure (OR: 5.50, 95%CI: 1.07-28.36) were associated with lack of susceptibility to penicillin. Bacteremia occurred significantly less frequently in penicillin-nonsusceptible infections (OR: 0.34, 95%CI: 0.14-0.84), possibly suggesting that lack of penicillin susceptibility is associated with lower virulence in S. pneumoniae.

Factors associated with penicillin-nonsusceptible pneumococcal infections in Brazil

Resistance of Streptococcus pneumoniae is a worldwide, growing problem. Studies of factors associated with resistance to penicillin have not been conducted in Brazil. The objective of the present study was to evaluate factors associated with infection by S. pneumoniae not susceptible to penicillin. A prevalence study was conducted including all patients with a positive culture for S. pneumoniae in a hospital from July 1991 to December 1992 and the year 1994. Of 165 patients identified, 139 were considered to have clinically relevant infections and 88 percent of them had invasive infections. All infections were community acquired and consisted of pneumonia (44 percent) and of central nervous system (19 percent), pelvic or abdominal (12 percent), upper airway or ocular (12 percent), primary bloodstream (9 percent) and skin and soft tissue (5 percent) infections. Mortality was 25 percent. Susceptibility to penicillin was present in 77.6 percent of the isolates; 21.8 percent were relatively resistant, and one isolate was resistant (minimal inhibitory concentration = 4 æg/ml). Multivariate analysis showed that age below 4 years (odds ratio (OR): 3.53, 95 percent confidence interval (95 percentCI): 1.39-8.96) and renal failure (OR: 5.50, 95 percentCI: 1.07-28.36) were associated with lack of susceptibility to penicillin. Bacteremia occurred significantly less frequently in penicillin-nonsusceptible infections (OR: 0.34, 95 percentCI: 0.14-0.84), possibly suggesting that lack of penicillin susceptibility is associated with lower virulence in S. pneumoniae

Randomized trial with itraconazole, ketoconazole and sulfadiazine in paracoccidioidomycosis.

Forty-two patients with active paracoccidioidomycosis were randomized to receive itraconazole (50-100 mg d(-1)), ketoconazole (200-400 mg d(-1)) or sulfadiazine (100-150 mg kg d(-1) up to 6 g d(-1)) for 4-6 months, followed by slow release sulfa until negativity of serological tests. All 14 patients in itraconazole and sulfadiazine groups and 13 in the ketoconazole group showed an adequate clinical response to the chemotherapy. One patient in the latter group showed treatment failure according to clinical and mycological criteria. The test of the hypothesis that the drugs reduced antibody levels up to ten months of treatment showed a p value equal to 0.0001 for itraconazole, 0.017 for ketoconazole and 0.0012 for sulfadiazine; this reduction was similar for the three groups. In this first randomized study for the treatment of paracoccidioidomycosis we could not show superiority of any one regimen over the others in the clinical and serological responses of patients with the moderately severe form of the disease.

Treatment of nosocomial pneumonia: an experience with meropenem.

This study aimed at evaluating the efficacy and safety of meropenem as first choice treatment for nosocomial pneumonia (NP) in intensive care units (ICU) in Hospital das Clínicas (HC) - University of São Paulo; a hospital with high incidence of antimicrobial resistance. Prospective, open, and non-comparative trial with meropenem were done in patients with ventilator-associated or aspiration NP in 2 ICUs at HC - University of São Paulo. Etiologic investigation was done through bronchoalveolar lavage and blood cultures prior to study entry. Twenty-five (25) critically ill patients with NP were enrolled (mean age 40 years). Ventilator-acquired pneumonia was responsible for 76% of cases and aspiration NP for 24%. Specific etiologic agents were identified and considered to be clinically and temporally responsible for NP in 11 (44%) patients. A. baumanii was responsible for 6 cases (55%), P. aeruginosa for 3 (27%), and S. aureus for 2 (18%). At completion of treatment, 19 patients (76%) showed either cure (48%) or improvement (28%) after use of meropenem therapy. Mortality was 12% at the end of therapy (8% after excluding 1 non-evaluable patient). After 4 to 6 weeks of follow-up, 12 (48%) patients had improved or been totally cured, and overall mortality was 24%. Clinical complications were observed in 11 patients (44%), with none of them definitely related to the study drug. Meropenem as monotherapy was effective and well-tolerated in most NP patients in our ICU. The low mortality rate in this study might have been due to first choice use of this drug. Controlled, drug comparative clinical trials are needed to support this preliminary observation.

Sexual transmission of hepatitis C virus.

In order to contribute to a better understanding of the forms of acquisition of hepatitis C virus (HCV) in Brazil, with special emphasis on sexual transmission, we determined the presence of HCV infection in regular partners and in non-sexual home communicants of blood donors seen at Fundação Pró-Sangue Hemocentro de São Paulo from January 1992 to July 1996. Of 154 blood donors with HCV infection (index cases), 111 had had regular partners for at least 6 months. Sixty-eight of 111 partners were evaluated for HCV infection. Of these, 8 (11.76%) were considered to have current or previous HCV infection; a history of sexually transmissible diseases and index cases with a positive HCV-RNA test were more prevalent among partners with HCV infection. Of the 68 index cases whose partners were studied, 56 had non-sexual home communicants. Of the total of 81 home communicants, 66 accepted to be evaluated for HCV infection. None of them was HCV-positive, suggesting that the high prevalence of HCV infection among partners may be attributed at least partially to sexual transmission.

Hepatitis C virus seroprevalence and risk factors among patients with HIV infection.

The objective of this study was to evaluate the prevalence and risk factors associated with HCV infection in a group of HIV seropositive patients. We analyzed the medical records of 1,457 patients. All patients were tested for HCV infection by third generation ELISA. Whenever possible, a sample of the positive patients was also tested for HCV by PCR. HCV positive patients were analyzed according to their risk factors for both infections. The prevalence of anti-HCV positive patients was 17.7% (258 patients). Eighty-two (82) of these patients were also tested by PCR and 81 were positive for HCV virus (98%). One hundred fifty-one (58.5%) were intravenous drug users (IDU); 42 (16.3%) were sexual partners of HIV patients; 23 (8.9%) were homosexual males; 12 (4.7%) had received blood transfusion; 61 (17.5%) had promiscuous sexual habits; 14 (5.4%) denied any risk factor; 12 (4.7%) were sexual partners of IDU. Two hundred four patients mentioned only one risk factor. Among them, 28 (10.9%) were sexual partners of HIV-positive patients. Although intravenous drug use was the most important risk factor for co-infection, sexual transmission seemed to contribute to the high HCV seroprevalence in this group of patients.

Prevalence of hepatitis B and C in the sera of patients with HIV infection in São Paulo, Brazil.

The objective of this study was to evaluate the prevalence of hepatitis B and C viruses in a group of HIV infected patients, followed at a single institution since 1996. 1,693 HIV positive patients (1,162 male, 531 female) were tested for HBV infection. Virological markers for HBV included HBsAg and total anti-HBc by ELISA. 1,457 patients (1,009 male, 448 female) were tested for HCV infection. Detection of HCV antibodies was carried out by ELISA. A sample of HCV antibody positive patients was tested for HCV by PCR to confirm infection. Of 1,693 patients tested for HBV, 654 (38.6%) and 96 (5.7%) were anti-HBc and HBsAg positive, respectively. Of 1, 457 patients tested for HCV, 258 (17.7%) were anti-HCV positive. 82 of these patients were also tested by PCR and 81 were positive (98%). Of 1,411 patients tested for HBV and HCV 26 (1.8%) were positive for both viruses.

Outer-membrane proteins pattern and detection of beta-lactamases in clinical isolates of imipenem-resistant Acinetobacter baumannii from Brazil.

In order to compare imipenem-sensitive and -resistant Acinetobacter baumannii strains isolated from three patients, ribotyping, plasmid, beta-lactamase detection and outer-membrane analysis were performed. Ribotyping and the use of a beta-lactam during the period when the strains were isolated suggested that they had a common origin and that resistance occurred in vivo. Outer membrane analysis showed no difference between susceptible and resistant strains with the exception of an A2 imipenem-resistant strain that lost a protein band of 31-36 kDa. Beta-lactamases were detected using isoelectric focusing in all strains (pI of 7.4). In addition, two beta-lactamases (pI of 5.9 and 6.7) were found in imipenem-resistant isolates. The double-disc technique demonstrated the presence of a beta-lactamase capable of imipenem inactivation in resistant strains. Plasmid analysis showed that all susceptible strains had the same pattern, one resistant strain did not have any plasmid, one had the same plasmid pattern of its susceptible pair and only one had a different pattern when compared with its susceptible pair.

Intravenous colistin as therapy for nosocomial infections caused by multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii.

Sixty nosocomial infections caused by Pseudomonas aeruginosa and Acinetobacter baumannii resistant to aminoglycosides, cephalosporins, quinolones, penicillins, monobactams, and imipenem were treated with colistin (one patient had two infections that are included as two different cases). The infections were pneumonia (33% of patients), urinary tract infection (20%), primary bloodstream infection (15%), central nervous system infection (8%), peritonitis (7%), catheter-related infection (7%), and otitis media (2%). A good outcome occurred for 35 patients (58%), and three patients died within the first 48 hours of treatment. The poorest results were observed in cases of pneumonia: only five (25%) of 20 had a good outcome. A good outcome occurred for four of five patients with central nervous system infections, although no intrathecal treatment was given. The main adverse effect of treatment was renal failure; 27% of patients with initially normal renal function had renal failure, and renal function worsened in 58% of patients with abnormal baseline creatinine levels. Colistin may be a good therapeutic option for the treatment of severe infections caused by multidrug-resistant P. aeruginosa and A. baumannii.