Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 24
Filter
1.
J Voice ; 36(4): 587.e1-587.e11, 2022 Jul.
Article in English | MEDLINE | ID: mdl-32800614

ABSTRACT

OBJECTIVE: To perform a cross-cultural adaptation into Italian and to analyse reliability and validity of the Transsexual Voice Questionnaire for male-to-female transsexuals (I-TVQMtF). STUDY DESIGN: Cross-sectional nonrandomized survey study. METHODS: For item-generation, a cross-cultural adaptation and translation process was performed following standard guidelines. Transgender women were consecutively recruited and asked to fill out the I-TVQMtF and a form on social, demographic and transition-related variables. Firstly, data collected from participants were used to perform confirmatory factor analysis, and to evaluate internal consistency and test-retest reliability Subsequently, convergent validity was evaluated comparing I-TVQMtF total scores with the two extra items addressing self-perception (SPVF) and aspiration (AVF) of voice femininity. To evaluate convergent validity, scores of the Italian version of the Voice Handicap Index were considered for comparisons. A correlation analysis was performed to verify potential association between I-TVQMtF scores and social, demographic and transition-related variables. RESULTS: Confirmatory factor analysis demonstrated that a two-factor model fits data better than the unidimensional one. Both internal consistency and test retest reliability of the I-TVQMtF were satisfactory. Negative correlations were highlighted between I-TVQMtF scores on one side and self-perception vocal functioning and aspiration vocal functioning on the other. Positive correlations between I-TVQMtF and Italian version of the Voice Handicap Index scores were also found. Finally, negative correlations were demonstrated between I-TVQMtF scores and time spent living in the female role. CONCLUSION: The I-TVQMtF appears to be a reliable and valid instrument for the assessment of voice-related quality of life in transgender women.


Subject(s)
Quality of Life , Transgender Persons , Cross-Cultural Comparison , Cross-Sectional Studies , Female , Humans , Male , Psychometrics , Reproducibility of Results , Surveys and Questionnaires , Voice Quality
2.
Health Econ Rev ; 10(1): 27, 2020 Aug 29.
Article in English | MEDLINE | ID: mdl-32860539

ABSTRACT

BACKGROUND: Since HIV+ treatment has become more effective, the average age of people living with HIV (PLWHIV) has increased, and consequently the incidence of developing comorbidities, making the clinical and economic management of HIV+ patients more complex. Limited literature exists regarding the management of comorbidities costs. This study is aimed at defining and comparing the total annual costs of comorbidities, in an Italian cohort of HIV and HIV/HCV patients, from the National Healthcare Service perspective. The authors hypothesised that there are higher costs, for patients with multiple comorbidities, and a greater consumption of resources for HIV/HCV co-infected patients versus HIV mono-infected patients. METHODS: An observational retrospective multi-centre health-economics study, enrolling HIV+ and HIV/HCV consecutive patients with at least one comorbidity, was conducted. The consecutive cases, provided by three Italian infectious diseases centres, were related to the year 2016. The enrolled patients were on a stable antiviral therapy for at least six months. Demographic and clinical information was recorded. Costs related to HIV and HCV therapies, other treatments, medical examinations, hospitalizations and outpatient visits were evaluated. Data from mono-infected and co-infected groups of patients were compared, and the statistical analysis was performed by t-tests, chi-square and ANOVA. A sub-analysis excluding HCV therapy costs, was also conducted. The hierarchical sequential linear regression model was used to explore the determinants of costs, considering the investigated comorbidities. All analyses were conducted with a significant level of 0.05. RESULTS: A total of 676 patients, 82% male, mean age 52, were identified and divided into groups (338 mono-infected HIV+ and 338 co-infected HIV/HCV patients), comparable in terms of age, gender, and demographic characteristics. A trend towards higher annual costs, for patients with multiple comorbidities was observed in HIV mono-infected patients (respectively € 8272.18 for patients without comorbidities and € 12,532.49 for patients with three or more comorbidities, p-value: 0.001). Excluding anti-HCV therapies costs, HIV/HCV co-infected patients generally required more resources, with statistically significant differences related to cardiovascular events (€10,116.58 vs €11,004.28, p-value: 0.001), and neurocognitive impairments events (€7706.43 vs €11,641.29 p- value: < 0.001). CONCLUSIONS: This study provides a differentiated and comprehensive analysis of the healthcare resources needed by HIV and HIV/HCV patients with comorbidities and may contribute to the decision process of resources allocation, in the clinical management of different HIV+ patient populations.

3.
Clin Infect Dis ; 71(16): 2276-2278, 2020 11 19.
Article in English | MEDLINE | ID: mdl-32407467

ABSTRACT

Little is known about the clinical outcomes of patients with human immunodeficiency virus infected with SARS-CoV-2. We describe 47 patients referred to our hospital between 21 February and 16 April 2020 with proven/probable COVID-19, 45 (96%) of whom fully recovered and 2 who died.


Subject(s)
COVID-19/complications , HIV Infections/complications , Adult , Antiviral Agents/therapeutic use , Female , Hospitalization , Humans , Italy , Male , Middle Aged , Prognosis , Retrospective Studies , Risk Factors , SARS-CoV-2 , COVID-19 Drug Treatment
4.
Sex Transm Infect ; 96(6): 451-456, 2020 09.
Article in English | MEDLINE | ID: mdl-31900319

ABSTRACT

OBJECTIVES: Transgender people are disproportionately affected by the HIV-1 epidemic. We evaluated the origin of HIV-1 variants carried by South American transgenders living in Milan by combining accurate phylogenetic methods and epidemiological data. METHODS: We collected 156 HIV-1 pol sequences obtained from transgender patients engaged in sex work (TSWs) followed between 1999 and 2015 at L. Sacco Hospital, Milan, Italy. Phylogenetic analyses were conducted by HIV-TRACE, MrBayes, MacClade and Beast programs. Reference sequences were retrieved from Los Alamos and local databases. Last negative testing or proxy data from clinical records of infected individuals were used to investigate the country of infection. RESULTS: Among South American TSWs, the most represented HIV-1 subtypes were B (70.5%), F1 (12.8%) and C (4.4%). Gene flow migrations of B subtype indicated significant fluxes from TSWs to Italians (21.3%) belonging to all risk groups (26.4% to heterosexuals (HEs), 18.9% to men who have sex with men (MSM), 15.1% to injecting drug users). The largest proportion of bidirectional fluxes were observed between Italians and TSWs (24.6%). For F1 subtype, bidirectional viral fluxes involved TSWs and Italians (7.1% and 14.3%), and a similar proportion of fluxes linked TSWs and Italian HEs or MSM (both 15.8%). Significant fluxes were detected from Italians to TSWs for subtype C involving both MSM (30%) and HEs (40%). Country of HIV-1 acquisition was identified for 72 subjects; overall, the largest proportion of patients with B subtype (73.5%) acquired HIV-1 infection in South America. CONCLUSIONS: Our results indicated that South American transgenders largely contribute to the heterogeneity of HIV-1 variants in our country. The high number of clusters based on all subtypes indicated numerous transmission chains in which TSWs were constantly intermixed with HEs and MSM. Our results strongly advocate interventions to facilitate prevention, diagnosis and HIV-1 care continuum among transgender people.


Subject(s)
Epidemics , Genes, pol/genetics , HIV Infections/epidemiology , HIV-1/genetics , Heterosexuality/statistics & numerical data , Sex Workers/statistics & numerical data , Transgender Persons/statistics & numerical data , Adult , Aged , Female , HIV Infections/virology , Humans , Italy/epidemiology , Male , Middle Aged , Molecular Epidemiology , Phylogeny , Sexual and Gender Minorities/statistics & numerical data , South America/ethnology
5.
Ther Drug Monit ; 42(2): 330-334, 2020 04.
Article in English | MEDLINE | ID: mdl-31743292

ABSTRACT

BACKGROUND: Carbamazepine and oxcarbazepine are potent modulators of metabolic enzymes. Hence, potential drug-drug interactions (DDIs) may occur between these 2 drugs and antiretrovirals. Here, we aimed to assess the relevance of these drug-drug interactions in real-life clinical settings. METHODS: Patients treated concomitantly with carbamazepine or oxcarbazepine and antiretrovirals for at least 3 months were considered. Data on therapeutic drug monitoring (TDM) of both antiepileptic and antiretrovirals as trough concentrations were collected. HIV-infected patients not concomitantly treated with antiepileptic drugs and who underwent TDM for antiretrovirals in the previous 2 years were considered as controls. RESULTS: Eleven HIV-positive patients prescribed carbamazepine or oxcarbazepine were identified. All the TDM evaluations for carbamazepine and oxcarbazepine that resulted were within the therapeutic ranges. TDM results of darunavir measured in these patients were comparable with values usually measured in the control group. Conversely, the trough concentrations for atazanavir and dolutegravir demonstrated significantly lower values when compared with values usually measured in HIV-infected patients not treated with antiepileptic drugs (190 ± 91 versus 546 ± 380 ng/mL; -65%, P < 0.001; 191 ± 78 versus 1096 ± 510 ng/mL; -83%, P < 0.001, respectively). CONCLUSIONS: Co-administration of carbamazepine or oxcarbazepine with atazanavir or dolutegravir should be avoided owing to the potential risk of virological failure; in case of these 2 drugs, the adoption of TDM is strongly advisable, eventually combining with increased antiretroviral doses.


Subject(s)
Anti-Retroviral Agents/pharmacokinetics , Anticonvulsants/pharmacology , Carbamazepine/pharmacology , Oxcarbazepine/pharmacology , Adult , Anti-Retroviral Agents/therapeutic use , Atazanavir Sulfate/pharmacokinetics , Atazanavir Sulfate/therapeutic use , Darunavir/pharmacokinetics , Darunavir/therapeutic use , Drug Interactions , Drug Monitoring , Female , HIV Infections/drug therapy , Heterocyclic Compounds, 3-Ring/pharmacokinetics , Heterocyclic Compounds, 3-Ring/therapeutic use , Humans , Male , Middle Aged , Oxazines/pharmacokinetics , Oxazines/therapeutic use , Piperazines/pharmacokinetics , Piperazines/therapeutic use , Pyridones/pharmacokinetics , Pyridones/therapeutic use
6.
Ticks Tick Borne Dis ; 10(6): 101257, 2019 10.
Article in English | MEDLINE | ID: mdl-31285164

ABSTRACT

Lyme borreliosis cases have been reported from Lombardy in northern Italy, where Ixodes ricinus is the main vector of Borrelia burgdorferi sensu lato. However, spatial and temporal variation in the incidence of Lyme borreliosis is not well understood. In the present study, based on new notified cases of Lyme borreliosis from 2000 to 2015, an average of 1.24 new cases per million residents per year was documented. New cases, georeferenced at the municipal level, were analyzed by retrospective space-time analysis (using SaTScan v. 9.3.1); and land cover, extrapolated from a Corine Land Cover dataset (using QGIS 2.8.1), was used to implement an environmental risk factor analysis. Firstly, a temporal high-risk cluster was detected in Lombardy: the relative risk of Lyme borreliosis was 3.73 times higher during 2008-2015 compared with the entire study period. Moreover, in a spatiotemporal high-risk cluster with a circular base, land cover consisting of wildland-urban interface, meadow, forest and meadow-forest transition were significantly higher compared to low-risk areas. Results of the present study demonstrate that the incidence of Lyme borreliosis is increasing in Lombardy and that environmental conditions are suitable for I. ricinus ticks infected with B. burgdorferi s.l.: citizens and health systems should be aware of Lyme borreliosis to reduce tick bites with personal protective behaviors and to avoid misdiagnosis, particularly within the area including the observed high-risk cluster. Economic resources should be invested to inform about methods to prevent tick bites, how to check people and pets after frequenting risk areas, and ways of removing the biting ticks when they are found.


Subject(s)
Environment , Lyme Disease/epidemiology , Spatio-Temporal Analysis , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Humans , Incidence , Infant , Italy/epidemiology , Lyme Disease/microbiology , Male , Middle Aged , Retrospective Studies , Risk , Risk Factors , Young Adult
8.
Ther Drug Monit ; 38(3): 407-13, 2016 06.
Article in English | MEDLINE | ID: mdl-26885814

ABSTRACT

BACKGROUND: We have developed and validated a high-performance liquid chromatographic method for the simultaneous quantification, in human plasma, of dolutegravir, a new human immunodeficiency virus (HIV) integrase inhibitor, and rilpivirine, a novel HIV nonnucleoside reverse transcriptase inhibitor. METHODS: An internal standard (quinoxaline) was added to plasma aliquots (500 µL), and a simple solid-phase extraction procedure was applied. Chromatographic separation of the drugs and internal standard was achieved with a gradient of acetonitrile and acetate buffer, and with an analytical run time of 25 minutes using an XBridge C18 column. The column eluate was monitored at 260 nm for dolutegravir and the internal standard and at 305 nm for rilpivirine. RESULTS: The method was linear in the range of 20-8000 and 20-2000 ng/mL for dolutegravir and rilpivirine, respectively (mean r ≥ 0.993 on 10 replicates for both analytes). Mean intraday and interday precision and inaccuracy were <15% for both compounds. The mean recovery was 73% and 80% for dolutegravir and rilpivirine, respectively. CONCLUSIONS: The high-performance liquid chromatography-ultraviolet method we developed showed a good analytical performance required for therapeutic drug monitoring of antiretrovirals, leading to potential improvements in HIV-infected patient care and laboratory management.


Subject(s)
Anti-HIV Agents/pharmacokinetics , Chromatography, High Pressure Liquid/methods , Heterocyclic Compounds, 3-Ring/pharmacokinetics , Rilpivirine/pharmacokinetics , Anti-HIV Agents/administration & dosage , Drug Monitoring/methods , HIV Integrase Inhibitors/administration & dosage , HIV Integrase Inhibitors/pharmacokinetics , Heterocyclic Compounds, 3-Ring/administration & dosage , Humans , Oxazines , Piperazines , Pyridones , Reproducibility of Results , Reverse Transcriptase Inhibitors/administration & dosage , Reverse Transcriptase Inhibitors/pharmacokinetics , Rilpivirine/administration & dosage
10.
J Infect Dis ; 200(10): 1616-22, 2009 Nov 15.
Article in English | MEDLINE | ID: mdl-19795979

ABSTRACT

Better understanding of the epidemiology and transmission patterns of human Pneumocystis should lead to improved strategies for preventing Pneumocystis pneumonia (PCP). We have developed a typing method for Pneumocystis jirovecii that is based on restriction fragment length polymorphism (RFLP) analysis after polymerase chain reaction amplification of an approximately 1300 base-pair region of the msg gene family, which comprises an estimated 50-100 genes/genome. The RFLP pattern was reproducible in samples containing >1000 msg copies/reaction and was stable over time, based on analysis of serial samples from the same patient. In our initial analysis of 48 samples, we found that samples obtained from different individuals showed distinct banding patterns; only samples obtained from the same patient showed an identical RFLP pattern. Despite this substantial diversity, samples tended to cluster on the basis of country of origin. In an evaluation of samples obtained from an outbreak of PCP in kidney transplant recipients in Germany, RFLP analysis demonstrated identical patterns in samples that were from 12 patients previously linked to this outbreak, as well as from 2 additional patients. Our results highlight the presence of a remarkable diversity in human Pneumocystis strains. RFLP may be very useful for studying clusters of PCP in immunosuppressed patients, to determine whether there is a common source of infection.


Subject(s)
Fungal Proteins/genetics , Membrane Glycoproteins/genetics , Pneumocystis carinii/genetics , Pneumonia, Pneumocystis/genetics , Bacterial Typing Techniques , Genotype , Humans , Pneumocystis carinii/isolation & purification , Polymorphism, Restriction Fragment Length , Polymorphism, Single Nucleotide/genetics
11.
J Antimicrob Chemother ; 64(6): 1282-90, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19858161

ABSTRACT

OBJECTIVES: First-line therapy for Pneumocystis jirovecii pneumonia (PCP) is trimethoprim/sulfamethoxazole. Few data exist to guide the choice of second-line therapy for patients failing or developing toxicity to first-line therapy. METHODS: A case note review of 1122 patients with 1188 episodes of HIV-associated PCP from three observational cohorts in Copenhagen, London and Milan, between 1989 and 2004, was conducted. RESULTS: Trimethoprim/sulfamethoxazole (962 PCP episodes, 81%) was the most frequently used first-line therapy, followed by intravenous pentamidine (87 episodes, 7%), clindamycin/primaquine (72 episodes, 6%) and 'other' (atovaquone, dapsone/pyrimethamine, trimetrexate or inhaled pentamidine; 67 episodes, 6%). Rates of unchanged therapy were trimethoprim/sulfamethoxazole = 79%, clindamycin/primaquine = 65% and pentamidine = 60% (P < 0.001). First-line therapy was changed because of failure in 82 (7%) episodes and because of toxicity in 198 (17%) episodes. Three month survival rates were trimethoprim/sulfamethoxazole = 85%, clindamycin/primaquine = 81% and pentamidine = 76% (P = 0.09). After adjustment for possible confounders, pentamidine was associated with a significantly greater risk of death at 3 months [hazard ratio (HR) = 2.0, 95% confidence interval (CI) = 1.2-3.4]. Second-line therapy survival rates differed: trimethoprim/sulfamethoxazole = 85%; clindamycin/primaquine = 87%; and pentamidine = 60% (P = 0.01). Multivariable time-updated Cox regression analysis showed a greater risk of death associated with pentamidine (HR = 3.3, 95% CI = 2.2-5.0), but not for clindamycin/primaquine, when both were compared with trimethoprim/sulfamethoxazole. CONCLUSIONS: Pentamidine was associated with a greater risk of death when used as first- and second-line therapy for HIV-associated PCP, and was associated with more treatment changes. Clindamycin/primaquine appeared superior to pentamidine as second-line therapy for PCP in patients failing or developing toxicity with trimethoprim/sulfamethoxazole. In patients failing first-line treatment with non-trimethoprim/sulfamethoxazole regimens, second-line therapy should be trimethoprim/sulfamethoxazole.


Subject(s)
AIDS-Related Opportunistic Infections/drug therapy , Acquired Immunodeficiency Syndrome/complications , Antifungal Agents/therapeutic use , Pneumocystis carinii/isolation & purification , Pneumonia, Pneumocystis/drug therapy , Adolescent , Adult , Aged , Clindamycin/therapeutic use , Cohort Studies , Denmark , Female , Humans , Italy , London , Male , Middle Aged , Pentamidine/therapeutic use , Primaquine/therapeutic use , Survival Analysis , Treatment Outcome , Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic use , Young Adult
12.
J Acquir Immune Defic Syndr ; 48(1): 63-7, 2008 May 01.
Article in English | MEDLINE | ID: mdl-18360286

ABSTRACT

BACKGROUND: Limited clinical data exist to guide the choice of second-line salvage treatment for AIDS-associated Pneumocystis jirovecii pneumonia (PCP). METHODS: We did a systematic search of MEDLINE for all randomized and observational studies of PCP treatment published up to August 2007 and included individual treatment data of AIDS-associated PCP from a tricenter study. We calculated pooled estimates of reported outcome of second-line treatment using averaged odds ratios (ORs). RESULTS: Twenty-nine studies with sufficient detail of second-line treatment and outcome, including data from 82 individual cases from the tricenter study, yielded a total of 468 PCP second-line treatment episodes. Response rates to second-line treatment were comparable for trimethoprim-sulfamethoxazole (TMP-SMX; 68%) and clindamycin-primaquine (73%) (OR for response = 2.1 [95% confidence interval (CI): 1.1 to 3.2] and 2.7 [95% CI: 1.3 to 4.0], respectively) but were considerably lower for intravenous pentamidine (44%; OR = 0.8 [95% CI: 0.6 to 1.0]). CONCLUSIONS: Clindamycin-primaquine is an alternative to intravenous pentamidine as second-line treatment for PCP in patients who fail treatment with TMP-SMX. TMP-SMX should be used as a second-line treatment for those failing first-line treatments with regimens other than TMP-SMX.


Subject(s)
AIDS-Related Opportunistic Infections/drug therapy , Clindamycin/therapeutic use , Pentamidine/therapeutic use , Pneumocystis carinii/isolation & purification , Pneumonia, Pneumocystis/drug therapy , Primaquine/therapeutic use , Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic use , Clindamycin/administration & dosage , Cohort Studies , Humans , Pneumonia, Pneumocystis/microbiology , Primaquine/administration & dosage , Salvage Therapy , Treatment Outcome
13.
J Acquir Immune Defic Syndr ; 45(5): 521-8, 2007 Aug 15.
Article in English | MEDLINE | ID: mdl-17558331

ABSTRACT

BACKGROUND: Two Pneumocystis jiroveci independent genomic regions, internal transcribed spacer (ITS) 1 and ITS2, and dihydropteroate synthase (DHPS) gene have been used for typing a cohort of HIV-infected Italian patients with P jiroveci pneumonia (PcP). METHODS: Bronchoalveolar lavage samples isolated from 207 HIV-infected adults were ITS and DHPS genotyped by DNA sequencing and by restriction fragment length polymorphism analysis, respectively. Mutant DHPS samples were cloned and ITS typed. Data on severity, treatment, and outcome of PcP were obtained by chart review. RESULTS: High diversity with 46 different ITS genotypes was observed. At the DHPS locus, 9.1% of samples analyzed were found to be mutated. A correlation was observed between DHPS mutants and greater severity of PcP, as defined by higher lactate dehydrogenase (P = 0.015) and need for intubation (P = 0.002), and worse outcomes, as defined by failure of sulfa treatment (P = 0.04), death, and/or relapse of PcP (P = 0.008). There was a significant difference in ITS genotype patterns between DHPS wild-type and mutants (P = 0.028). CONCLUSIONS: The present data suggest the absence of a correlation between P jiroveci ITS types and specific clinical characteristics. DHPS mutations correlate with possible failure of anti-P jiroveci sulfa therapy, and a trend of association is shown between DHPS mutations and some clinical PcP features.


Subject(s)
AIDS-Related Opportunistic Infections/microbiology , Genes, Viral , HIV , Pneumocystis carinii/genetics , Pneumonia, Pneumocystis/microbiology , Viral Proteins/genetics , Adult , Aged , DNA, Intergenic/genetics , Dihydropteroate Synthase/genetics , Disease Progression , Female , Humans , Italy , Male , Middle Aged , Mutation , Pneumonia, Pneumocystis/drug therapy , Pneumonia, Pneumocystis/pathology , Polymerase Chain Reaction , Polymorphism, Genetic , Species Specificity , Treatment Outcome , Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic use
18.
Int Arch Allergy Immunol ; 140(1): 82-8, 2006.
Article in English | MEDLINE | ID: mdl-16549936

ABSTRACT

The case of a 20-year-old patient, affected by X-linked agammaglobulinaemia (XLA), who developed severe pneumonia from Pneumocystis jiroveci (formerly Pneumocystis carinii) (PCP), is reported. This infection usually affects patients with AIDS, children affected by severe combined immunodeficiency or hypogammaglobulinaemia with hyperimmunoglobulin M, or patients undergoing severe immunosuppression. The XLA patient developed PCP during therapy with steroids and cyclosporine A, carried out for several months, due to an extended skin vasculitis, accompanied by general symptoms. The pneumonia had a severe clinical course, requiring a long hospitalization. At the diagnosis of PCP, immunosuppressive therapy was suspended and the patient recovered after a long-term trimethoprim/sulfamethoxazole therapy. Immunological studies revealed an unexpected normal number of CD4+ and CD8+ T cells. The two subsets had an exclusive naïve phenotype (95% CD4+CD45RA+CD62L+ and 89% CD8+CD45RA+CD62L+ cells), with an absence of primed cells. Lymphoproliferative responses to P. carinii and recall antigens as well as to mitogens were extremely deficient. During the follow-up, memory cells appeared with recovery of the lymphoproliferative response to mitogens and maintained defective responses to antigens. This is one of the few reported XLA cases experiencing severe PCP. In this patient, the infection became clinically evident during immunosuppressive therapy. We believe that the absence of functional activities, despite a normal level of T lymphocyte counts, sustained this long-lasting infection. Thus, the CD4+ and CD8+ T cell count evaluation, without functional studies, may not be per se sufficient for predicting the risk of a severe clinical course of PCP in patients undergoing immunosuppression.


Subject(s)
Agammaglobulinemia/drug therapy , Genetic Diseases, X-Linked/drug therapy , Immunosuppressive Agents/therapeutic use , Pneumocystis carinii/immunology , Pneumonia, Pneumocystis/drug therapy , Adult , Agammaglobulinemia/immunology , Agammaglobulinemia/microbiology , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Cells, Cultured , Genetic Diseases, X-Linked/immunology , Genetic Diseases, X-Linked/microbiology , Humans , Infant , Lymphocyte Count , Lymphocyte Subsets/immunology , Male , Pneumonia, Pneumocystis/immunology
19.
Emerg Infect Dis ; 10(10): 1721-8, 2004 Oct.
Article in English | MEDLINE | ID: mdl-15504256

ABSTRACT

Pneumocystis pneumonia (PCP) remains a major cause of illness and death in HIV-infected persons. Sulfa drugs, trimethoprim-sulfamethoxazole (TMP-SMX) and dapsone are mainstays of PCP treatment and prophylaxis. While prophylaxis has reduced the incidence of PCP, its use has raised concerns about development of resistant organisms. The inability to culture human Pneumocystis, Pneumocystis jirovecii, in a standardized culture system prevents routine susceptibility testing and detection of drug resistance. In other microorganisms, sulfa drug resistance has resulted from specific point mutations in the dihydropteroate synthase (DHPS) gene. Similar mutations have been observed in P. jirovecii. Studies have consistently demonstrated a significant association between the use of sulfa drugs for PCP prophylaxis and DHPS gene mutations. Whether these mutations confer resistance to TMP-SMX or dapsone plus trimethoprim for PCP treatment remains unclear. We review studies of DHPS mutations in P. jirovecii and summarize the evidence for resistance to sulfamethoxazole and dapsone.


Subject(s)
Dihydropteroate Synthase/genetics , Drug Resistance, Fungal/genetics , Mutation , Pneumocystis carinii/enzymology , Sulfones/pharmacology , Anti-Infective Agents/administration & dosage , Anti-Infective Agents/pharmacology , Anti-Infective Agents/therapeutic use , Dapsone/pharmacology , Dihydropteroate Synthase/metabolism , Gene Expression , Humans , Pneumocystis carinii/drug effects , Pneumocystis carinii/genetics , Pneumonia, Pneumocystis/drug therapy , Pneumonia, Pneumocystis/mortality , Risk Factors , Sulfamethoxazole/pharmacology , Sulfones/therapeutic use , Trimethoprim/pharmacology
SELECTION OF CITATIONS
SEARCH DETAIL
...