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1.
Medicine (Baltimore) ; 85(3): 139-146, 2006 May.
Article in English | MEDLINE | ID: mdl-16721256

ABSTRACT

An unexplained resurgence of Group A streptococci (GAS) infections has been observed since the mid-1980s in the United States and Europe, particularly among intravenous drug users (IDUs). Several risk factors have been identified. Mutations in the capsule synthesis regulator genes (csrRS) have been associated with an increase in virulence. From January 1998 to December 2003, we conducted a prospective and retrospective descriptive analysis of invasive GAS soft-tissue infections in IDUs in Barcelona, Spain. Clinical features were collected, and we conducted a surveillance study to identify risk factors associated with GAS soft-tissue infections. We analyzed chromosomal DNA by low cleavage restriction enzymes and used pulsed-field gel electrophoresis (PFGE) and variable gene sequence typing (VGST) of the emm gene to disclose the epidemiologic relationship between the strains. We analyzed the influence of clonality (M-type) and mutations in csrRS genes of these strains on clinical features. We identified 44 cases, all of which were grouped in 3 clusters: fall 2000, fall 2002, and fall 2003. Cellulitis with or without abscesses (75%) and fever (90.9%) were the most common clinical manifestations. Distant septic complications were infrequent (18.2%). Although all patients had severe infections (mainly bacteremic needle abscesses), their outcome with antibiotic therapy, usually beta-lactam, was successful in all cases. However, surgery was needed in 40.9% of patients. Through the surveillance study we found that infected patients had a higher number of drug injections per day (odds ratio [OR], 18.84; 95% confidence interval [CI], 4.83-79.4; p<0.00001), shared paraphernalia for drug use more frequently (OR, 11.11; 95% CI, 3.24-39.04; p<0.0001), were in a higher proportion both currently unemployed and homeless (OR, 4.22; 95% CI, 1.5-12.15; p<0.0001), were not in a methadone maintenance program (OR, 0.03; 95% CI, 0-0.19; p<0.00001), and more often bought drugs at a specific site (OR, 33.92; 95% CI, 7.44-174.93; p<0.00001) and from a specific dealer (OR, 72; 95% CI, 8-3090; p<0.00001), compared with patients not infected. The fall 2000 cluster was polyclonal, whereas the other 2 clusters were mainly due to the same strain of GAS (emm 25.2), and were defined as epidemic outbreaks. Clinically, the cases due to the clonal strain presented abscesses and needed surgery more frequently (p<0.001 and p=0.005, respectively). On the other hand, mutations in the csrRS genes were not associated with invasive GAS soft-tissue infection. There has been an increase in the number of cases of invasive GAS soft-tissue infections in IDUs in Barcelona, which seems to be related to drug users' habits and their socioeconomic status. Clonality (emm 25.2) but not mutations in the csrRS genes was associated with more severe GAS soft-tissue infections.


Subject(s)
Cross Infection/epidemiology , Soft Tissue Infections/epidemiology , Streptococcal Infections/epidemiology , Streptococcus pyogenes/isolation & purification , Substance Abuse, Intravenous/epidemiology , Adolescent , Adult , Anti-Bacterial Agents/therapeutic use , Cluster Analysis , Cross Infection/drug therapy , Cross Infection/microbiology , Disease Outbreaks , Electrophoresis, Gel, Pulsed-Field , Female , Humans , Male , Middle Aged , Molecular Epidemiology , Mutation , Population Surveillance , Prospective Studies , Restriction Mapping , Retrospective Studies , Risk Factors , Sequence Analysis, DNA , Soft Tissue Infections/drug therapy , Soft Tissue Infections/microbiology , Spain/epidemiology , Streptococcal Infections/drug therapy , Streptococcal Infections/microbiology , Streptococcus pyogenes/drug effects , Streptococcus pyogenes/genetics , Substance Abuse, Intravenous/complications , Substance Abuse, Intravenous/microbiology , beta-Lactams/therapeutic use
2.
HIV Clin Trials ; 5(2): 65-73, 2004.
Article in English | MEDLINE | ID: mdl-15116281

ABSTRACT

OBJECTIVE: To assess the effectiveness of a simplified therapy for very nonadherent patients who had previously failed with HAART. METHOD: We performed a prospective open-label study of antiretroviral-experienced patients. Dosing schedule comprised (co-formulated) zidovudine, lamivudine, and abacavir bid. Eligible patients had to have plasma HIV RNA >5000 copies/mL, previous therapy, and very poor adherence to the medication regimen. RESULTS: Eighty-five patients were included (mean viral load, 4.4 log/mL; mean CD4, 240 cells/mL; IDUs, 78%; methadone maintenance program, 42%; AIDS, 28%). Number of previous therapies: one, 53%; two, 28%; three or more, 19%. In the intent-to-treat analysis at 1 year, 38 patients (44.7%) achieved viral load below 500 copies/mL. Adherence greater than 90% of prescribed drugs was reported in 49% of patients, adverse events were reported in 17.6%, mortality in 6%, and lost to follow-up in 26%. The factors associated with virologic failure were nonadherence (odds ratio [OR], 4.4; 95% CI 1.5-12.3), baseline CD4 cell count <200 cells/mL (OR, 3.4; 95% CI 1.3-8.9; p =.01), and more than one previous treatment (OR, 2.7; 95% CI 1.1-6.9). CONCLUSION: Regarding previously very nonadherent patients, this simplified combination therapy containing three NRTIs obtained satisfactory results in ART-experienced patients. However, more aggressive interventions to enhance adherence are needed to improve results.


Subject(s)
Anti-HIV Agents/administration & dosage , HIV Infections/drug therapy , Reverse Transcriptase Inhibitors/administration & dosage , Adult , Antiretroviral Therapy, Highly Active , CD4 Lymphocyte Count , Dideoxynucleosides/administration & dosage , Drug Administration Schedule , Female , Humans , Lamivudine/administration & dosage , Male , Prospective Studies , Spain , Treatment Failure , Treatment Outcome , Treatment Refusal , Viral Load , Zidovudine/administration & dosage
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