An insight into the drug resistance profile & mechanism of drug resistance in Neisseria gonorrhoeae.

Among the aetiological agents of treatable sexually transmitted diseases (STDs), Neissseria gonorrhoeae is considered to be most important because of emerging antibiotic resistant strains that compromise the effectiveness of treatment of the disease - gonorrhoea. In most of the developing countries, treatment of gonorrhoea relies mainly on syndromic management rather than the aetiological based therapy. Gonococcal infections are usually treated with single-dose therapy with an agent found to cure > 95 per cent of cases. Unfortunately during the last few decades, N. gonorrhoeae has developed resistance not only to less expensive antimicrobials such as sulphonamides, penicillin and tetracyclines but also to fluoroquinolones. The resistance trend of N. gonorrhoeae towards these antimicrobials can be categorised into pre-quinolone, quinolone and post-quinolone era. Among the antimicrobials available so far, only the third-generation cephalosporins could be safely recommended as first-line therapy for gonorrhoea globally. However, resistance to oral third-generation cephalosporins has also started emerging in some countries. Therefore, it has become imperative to initiate sustained national and international efforts to reduce infection and misuse of antibiotics so as to prevent further emergence and spread of antimicrobial resistance. It is necessary not only to monitor drug resistance and optimise treatment regimens, but also to gain insight into how gonococcus develops drug resistance. Knowledge of mechanism of resistance would help us to devise methods to prevent the occurrence of drug resistance against existing and new drugs. Such studies could also help in finding out new drug targets in N. gonorrhoeae and also a possibility of identification of new drugs for treating gonorrhoea.

Tratamento da paracoccidioidomicose: estudo retrospectivo de 500 casos. II - Avaliaçäo dos resultados terapêuticos com sulfanilamídicos, anfotericina B, associaçäo sulfametoxazol/trimetoprim, cetoconazol e miconazol / Treatment of paracoccidioidomycosis; retrospective: retrospective study of 500 cases. II - Evaluation of therapeutic results with sulfonamides, amphotericin B, ketoconazole and miconazole

Säo analisados rretrospectivamente 500 pacientes com paracoccidioidomicose antendidos no Hospital Evandro Chagas da Fundaçäo Oswaldo Cruz, Rio de janeiro, no período de 1960 a 1986. Os resultados ao término do tratamento com o emprego dos sulganilamídicos, anfotericina B, associaçäo sulfametoxazol/trimetoprim, cetoconazol e miconazol mostraram eficácia semelhante. A sulfamidoterapia curou a doença, principalmente da forma clínica tipo adulto; a anfotericina B, eficaz em todas as formas clínicas da doença, mostrou-se comparativamente melhor quando complementadas com sulfanilamídicos ou imidazólico do que a aplicaçäo isolada. A associaçäo sulfametoxazol/trimetoprim cura a doença, mas näo foi útil nos casos resistentes aos sulfamídicos. O cetoconazol foi eficáz, inclusive em casos resistentes aos outros tratamentos; encontramos os piores resultados na forma clínica tipo juvenil e o miconazol cura a doença na forma clínica tipo adulto. As drogas foram bem toleradas mas em todos os casos tratados com a anfotericina B ocorreram efeitos cerebrais

Mefloquine sulfadoxine pyrimethamine (MSP) combination delays in vitro emergence of mefloquine resistance in multiple drug resistant Plasmodium falciparum.

Sulfadoxine-pyrimethamine-resistant and chloroquine resistant, but mefloquine sensitive (MIC 5 x 10(-9] isolates of Plasmodium falciparum were used to study the emergence of mefloquine resistance. The continuously cultured isolates which were exposed intermittantly to varying concentrations of mefloquine alone became insensitive to the drug at 1 x 10(-7) M after 12 months, whereas the culture line exposed to the combination of mefloquine, sulfadoxine and pyrimethamine became only slightly insensitive to mefloquine (MIC 2 x 10(-8]. Thus, the efficacy of mefloquine may be prolonged through use in combination with sulfadoxine-pyrimethamine.

Chemotherapeutic malaria control operation by single dose of Fansidar plus primaquine in North Sumatra, Indonesia.

Selective age group treatment and village scale chemotherapeutic malaria control operation were carried out in east-coast villages in North Sumatra, Indonesia in 1987/1988. A single dose of Fansidar plus primaquine was adopted as the drug regimen to cut the transmission of malaria at the gametocyte stage. After the treatment on day seven, the gametocyte positive rate was reduced to only 2.7% in 72 Plasmodium falciparum gametocyte carriers. A significant reduction of P. falciparum prevalence in the community was observed after successive selective age group treatment in primary school, however P. vivax prevalence persisted. Village scale active case detection was carried out by one health center staff and two village health volunteers. After eight months P. falciparum prevalence was reduced from 14% to 1%. As the result of the chemotherapeutic control activities covering high-prevalence villages in the coastal area, malaria prevalence in 1988 became very low, as compared with the status in 1985/1986.

Quimioterapia das micoses profundas

As doenças humanas causadas por fungos patogênicos säo classificados em quatro grupos naturais: micose superficiais, cutâneas, subcutâneas e sistêmicas. A expressäo micoses profundas designa o agrupamento de doenças que englobam as micoses subcutâneas, as micoses sistêmicas e as micoses oportunistas de localizaçäo subcutânea e sistêmica. O trabalho a seguir apresenta um estudo dos principais antifúngicos e antibióticos empregados no controle das micoses

The effect of mefloquine-sulfadoxine-pyrimethamine vs quinine on patients with complicated falciparum malaria.

Sixty-six patients with complicated falciparum malaria (defined as anaemia, hyperpyrexia, jaundice, or more than 2% of RBC parasitised) were studied. Patients with cerebral signs and symptoms were not included in the study. Patients were randomised in pairs to receive either mefloquine 750 mg, sulfadoxine 1500 mg and pyrimethamine 75 mg (MSP) single oral dose or quinine (10 mg/kg tds X 7 days oral therapy). All the patients were admitted in hospital for 7 days and were followed on days 14, 21 and 28. All patients survived. The parasite clearance times in MSP treated patients were significantly shorter then those treated with quinine. There was no difference in fever clearance time in the two groups of patients. One patient was resistant to MSP at RII level and 5 patients were resistant at RI level. Among patients treated with quinine 3 patients were resistant at RI level.

Sulfadoxine-pyrimethamine resistant falciparum malaria in Thai children.

Sixty-eight children with uncomplicated falciparum malaria admitted to the Hospital for Tropical Diseases in Bangkok during April-December 1980 were randomly divided into 3 groups and given 3 regimens. Group 1 of 27 cases were treated with a single dose of sulfadoxine 20 mg per kg body wt and pyrimethamine 1.0 mg per kg body wt. Two cases (7.4%) were cured (S) while 4 cases (14.8%) showed RI failure, 17 cases (63.0%) RII failure and 4 cases (14.8) RIII failure. In Group 2, 18 cases were treated with a single dose of sulfadoxine 30 mg per kg body wt and pyrimethamine 1.5 mg per kg body wt. Two cases (11.1%) were cured (S), while 7 cases (38.9%) showed RI failure, 7 cases (38.9%) RII failure and 2 cases (11.1%) RIII failure. In Group 3, 23 cases were treated with quinine 10 mg base per kg body wt 8 hourly for 5 days plus sulfadoxine 20 mg per kg body wt and pyrimethamine 1.0 mg per kg body wt, single dose given with the last dose of quinine. Thirteen cases (56.5%) were cured (S), while 10 cases (43.5%) showed RI failure.

Treatment of falciparum malaria with sulfalene-pyrimethamine versus sulfadoxine-pyrimethamine.

The study was carried out in 89 uncomplicated falciparum malaria adult cases admitted to Paholpol-Phayuhasena Hospital, Kanchanaburi Province, Thailand, during July 1979 and March 1980. The patients were divided alternatively into 2 groups. Group I, 46 patients, were treated with a single dose of 1000 mg sulfalene and 50 mg pyrimethamine (2 tablets of Metakelfin). Group II, 43 patients, were treated with 1000 mg sulfadoxine and 50 mg pyrimethamine (2 tablets of Fansidar). The parasitemia was cleared within 7 days in 7 cases (15.2%) of group I and in 11 cases (25.6%) of group II. The results of both groups are not statistically significant. It is concluded that the success rate of Fansidar in the treatment of falciparum malaria is decreasing in Thailand and Metakelfin can be used in the treatment of falciparum malaria either alone in mild cases or in combination with quinine as an alternative to Fansidar.

Clearance of falciparum parasitaemia with a single dose sulfadoxine-pyrimethamine in Vientiane, Laos.

A total of 49 semi-immune Laotians aged 3 to 49 years, with falciparum malaria were treated with a single dose of sulfadoxine pyrimethamine (1500 mg, 75 mg, adult dose), in Vientiane, Laos. On day 7 after treatment the 49 cases were asymptomatic with complete disappearance of patent asexual parasitaemia. The result is compared with that obtained from treating 48 similar cases with a standard dose of chloroquine over 3 days.