Susceptibility of Escherichia coli from Community-Acquired Urinary Tract Infection to Fosfomycin, Nitrofurantoin, and Temocillin in Korea

With increase of multi-drug resistant Escherichia coli in community-acquired urinary tract infections (CA-UTI), other treatment option with a therapeutic efficacy and a low antibiotic selective pressure is necessary. In this study, we evaluated in vitro susceptibility of E. coli isolates from CA-UTI to fosfomycin (FM), nitrofurantoin (NI), temocillin (TMO) as well as trimethoprim-sulfamethoxazole (SMX), ciprofloxacin (CIP) and cefepime (FEP). The minimal inhibitory concentrations were determined by E-test or agar dilution method according to the Clinical and Laboratory Standards Institute guidelines, using 346 E. coli collected in 12 Korean hospitals from March 2010 to February 2011. FM, NI and TMO showed an excellent susceptibility profile; FM 100% (346/346), TMO 96.8% (335/346), and NI 99.4% (344/346). Conversely, resistance rates of CIP and SMX were 22% (76/346) and 29.2% (101/349), respectively. FEP still retained an activity of 98.5%. In Korea, NI and TMO in addition to FM are a good therapeutic option for uncomplicated CA-UTI, especially for lower UTI.

Susceptibility of Escherichia coli from Community-Acquired Urinary Tract Infection to Fosfomycin, Nitrofurantoin, and Temocillin in Korea

With increase of multi-drug resistant Escherichia coli in community-acquired urinary tract infections (CA-UTI), other treatment option with a therapeutic efficacy and a low antibiotic selective pressure is necessary. In this study, we evaluated in vitro susceptibility of E. coli isolates from CA-UTI to fosfomycin (FM), nitrofurantoin (NI), temocillin (TMO) as well as trimethoprim-sulfamethoxazole (SMX), ciprofloxacin (CIP) and cefepime (FEP). The minimal inhibitory concentrations were determined by E-test or agar dilution method according to the Clinical and Laboratory Standards Institute guidelines, using 346 E. coli collected in 12 Korean hospitals from March 2010 to February 2011. FM, NI and TMO showed an excellent susceptibility profile; FM 100% (346/346), TMO 96.8% (335/346), and NI 99.4% (344/346). Conversely, resistance rates of CIP and SMX were 22% (76/346) and 29.2% (101/349), respectively. FEP still retained an activity of 98.5%. In Korea, NI and TMO in addition to FM are a good therapeutic option for uncomplicated CA-UTI, especially for lower UTI.

Chloroquine resistant Plasmodium falciparum malaria in Osogbo Nigeria: efficacy of amodiaquine + sulfadoxine-pyrimethamine and chloroquine + chlorpheniramine for treatment

Chloroquine (CQ) resistance in Plasmodium falciparum contributes to increasing malaria-attributable morbidity and mortality in Sub-Saharan Africa. Despite a change in drug policy, continued prescription of CQ did not abate. Therefore the therapeutic efficacy of CQ in uncomplicated falciparum malaria patients was assessed in a standard 28-day protocol in 116 children aged between six and 120 months in Osogbo, Southwest Nigeria. Parasitological and clinical assessments of response to treatment showed that 72 (62.1 percent) of the patients were cured and 44 (37.9 percent) failed the CQ treatment. High initial parasite density and young age were independent predictors for early treatment failure. Out of the 44 patients that failed CQ, 24 received amodiaquine + sulphadoxine/pyrimethamine (AQ+SP) and 20 received chlorpheniramine + chloroquine (CH+CQ) combinations. Mean fever clearance time in those treated with AQ+SP was not significantly different from those treated with CH+CQ (p = 0.05). There was no significant difference in the mean parasite density of the two groups. The cure rate for AQ+SP group was 92 percent while those of CH+CQ was 85 percent. There was a significant difference in parasite clearance time (p = 0.01) between the two groups. The 38 percent treatment failure for CQ reported in this study is higher than the 10 percent recommended by World Health Organization in other to effect change in antimalarial treatment policy. Hence we conclude that CQ can no more be solely relied upon for the treatment of falciparum malaria in Osogbo, Nigeria. AQ+SP and CH+CQ are effective in the treatment of acute uncomplicated malaria and may be considered as useful alternative drugs in the absence of artemisinin-based combination therapies.

Effects of pyrimethamine-sulphadoxine, chloroquine plus chlorpheniramine, and amodiaquine plus pyrimethamine-sulphadoxine on gametocytes during and after treatment of acute, uncomplicated malaria in children

The effects of pyrimethamine-sulphadoxine (PS), chloroquine plus chlorpheniramine, a H1 receptor antagonist that reverses chloroquine resistance in Plasmodium falciparum in vitro and in vivo (CQCP), and amodiaquine plus pyrimethamine-sulphadoxine (AQPS) on gametocyte production were evaluated in 157 children with acute, symptomatic, uncomplicated falciparum malaria who were treated with these drugs. PS was significantly less effective than CQCP or AQPS at clearing asexual parasitaemia or other symptoms of malaria. Gametocyte carriage on days 3, 7, and 14 were significantly higher in those treated with PS. The ratio of the density (per æl blood) of peripheral young gametocyte (PYG), that is, < stage III to peripheral mature gametocyte (PMG), that is, stage IV and V, an index of continuing generation of gametocytes, rose to 1 by day 7 of treatment in those treated with PS, but remained consistently below 1 in the other treatment groups. PYG-PMG density ratio increased significantly from day 0-14 in those treated with PS and CQCP (chi2 = 76, P = 0.000001 and chi2 = 42.2, P = 0.00001, respectively) but decreased significantly in those treated with AQPS (chi2 = 53.2, P = 0.000001). Both PS-sensitive and -resistant infections generated PYG (18 of 29 vs 13 of 20, chi2 = 0.04, P = 0.93) but PYG was present only in those with resistant response to CQCP. Combination of PS with amodiaquine (AQ), that is, (AQPS) resulted in less production of PYG, but in this setting, PYG was not indicative of response to AQPS. These data indicate that PS enhanced production or release of young gametocytes when used alone, but generated less young gametocytes when used in combination with AQ. PYG may be used as an indicator of response to CQCP but not PS or PS-based combination drugs.

Pyrimethamine-sulfadoxine treatment of uncomplicated Plasmodium falciparum malaria in Lao PDR.

A 28-day in vivo treatment trial to evaluate the efficacy of pyrimethamine/sulfadoxine (Fansidar, PS) was conducted in 21 Lao patients with uncomplicated Plasmodium falciparum malaria. Sixteen patients (76%) were completely cured with PS without any reappearance of asexual stage parasitemia during the follow-up examination. On the other hand, 5 patients (24%) failed to respond to this trial medication, resulting in recrudescence of asexual stage P. falciparum malaria. PS resistance resulted in higher prevalence of post-treatment gametocytemia, 25% gametocyte carriers among PS sensitive cases versus 75% of the resistant cases. These findings suggest that although the level of PS resistance is still valid for treatment of malaria in the study area of Lao PDR, post-treatment induction of gametocytemia among resistant cases may result an increase in transmission rate of PS resistant falciparum malaria.

Malaria: tratamiento y quimioprofilaxis / Malaria: treatment and prophylaxis

Malaria es una patología reemergente en el mundo y en América en particular; se revisan aspectos epidemiológicos de la enfermedad en Perú. Las nuevas medidas de control propuestas por la OMS para reducir la mortalidad por malaria y su impacto socio-económico son: diagnóstico y tratamiento precoz de los pacientes; control del vector; detección y contención de epidemias; investigación local básica y aplicada que permita evaluar periódicamente la situación de malaria. Se describen los fármacos y esquemas terapéuticos y profilácticos recomendados para el manejo de la malaria

Monitoring efficacy of commonly used antimalarials by a 14-day in-vivo test in a new settler's camp in endemic zone at Cox's Bazar.

The study was done in a new settler's camp "Barachara" under Sadar thana of Cox's Bazar district. It has a total population of 784 of all age groups, registered in the middle of the study period. A prospective evaluation of all cases of fever were done over 12 months, to see the pattern of febrile illness among the population and to compare the therapeutic efficacy of two alternative drug regimens for uncomplicated falciparum malaria (UM). Blood for malarial parasite (MP) was done in all cases of fever and was treated in line with the new clinical case definitions and treatment guidelines for malaria in Bangladesh. Slide positive UM cases were subjected to a "14-day in-vivo test" for therapeutic efficacy testing of antimalarial agents. The two drug regimens were randomised by lottery--a) 3 days oral chloroquine plus single dose sulphadoxin/pyrimethamine (CQ + SP) and, b) 3 days oral quinine plus single dose sulphadoxin/pyrimethamine (Q3 + SP). Drug administration was supervised by the field assistant and was followed up on days 3, 7 and 14 for blood slide examinations and clinical assessment. Sensitive response was observed in 79% of the cases in the CQ + SP group and 84% in the Q3 + SP group. Early treatment failure (persistently febrile and parasitaemic on days 3 or 7) was observed in 16% in the CQ + SP group and 9% in the Q3 + SP group. Both the evaluated drug regimens had less than 20% failures and can be used as alternative first line agents and Q3 + SP regimens can also be used as the second line agents for treatment failure (to chloroquine and/or SP) UM cases in the study area.

Avaliação clínica do quinino para o tratamento de malária por Plasmodium falciparum / The clinical evaluation of quinine for the treatment of Plasmodium falciparum malaria

O quinino foi o primeiro medicamento correntemente usado para tratar malária, tendo sido abandonado seu emprego principalmente após o início do emprego da cloroquina. A partir da década de 60 com o surgimento de resistência do P. falciparum à cloroquina voltou-se a utilizar o quinino isolado ou em associação para tratar tal infecção. Com o objetivo de avaliar clinicamente a resposta ao quinino de pacientes com malária por P. falciparum, analisamos os prontuários de 484 pacientes atendidos no Laboratório de Malária da SUCEN e acompanhados por pelo menos 28 dias, e que haviam recebido diferentes esquemas terapêuticos com quinino isolado ou em associação. Do total, 81,0% dos pacientes foram curados pelos esquemas empregados, sendo que dos restantes apenas 0,6% foram R2 e nenhum R3. Tais resultados mostram ainda que esquemas contendo quinino podem ser adequados para tratar malária por P. falciparum.

Quinine was the first antimalarial drug to be employed and also the first resistance was noticed to. After 1960 quinine urged to be reintroduced in routine therapy alone or in combination. Aiming at evaluating the effectiveness of different schedules we studied 484 patients seen at the Malaria Laboratory. We used quinine alone in 126 patients, quinine plus sulfadoxine and pyrimethamine in 119 patients and quinine plus tetracycline in 239 patients. The results shown that 81% of all patients were treated with success and only 0.6% were R2. and there is no R3. We emphasize a high resistance rate to quinine either alone (23.1%) or associated to sulfadoxine and pyrimethamine (37.8%). A higher resistance rate seen with the combination might be linked to the smaller dose of quinine used in that instance. It is worth noting the high cure rate with the quinine-tetracycline association.

Phase III double-blind comparative study of Fansimef and Lariam for the curative treatment of Plasmodium falciparum infections in Thailand.

A double-blind comparative study of Fanismef-mefloquine/sulfadoxine/pyrimethamine (MSP) and Lariam-mefloquine (MEF) for the treatment of falciparum malaria, was carried out at malaria clinics in Kanchanaburi, in western Thailand, in the years 1987 and 1988. The cure rates obtained were 96% for the MSP group and 93% for the MEF and there was no significant difference. Vomiting and diarrhea were common side effects in both the MSP and MEF groups. Less common side effects were epigastric pain, minor skin rashes and dizziness. Significant differences in vomiting and epigastric pain only occurred in the patients who did not have these symptoms before treatment: vomiting MSP 23%, MEF 8%, epigastric pain MSP 22% and MEF 11%.

Antimalarial and toxic effect of triple combination of pyronaridine, sulfadoxine and pyrimethamine.

The triple combination of pyronaridine, sulfadoxine and pyrimethamine which has been proven to be efficient in delaying emergence of drug resistance of rodent malarial parasites was further studied for potential application to malaria control. The antimalarial effect of the triple combination on Plasmodium berghei ANKA-infected mice and the toxic effects in mice and rats were additive. A single dose of pyronaridine 500 mg in combination with sulfadoxine, 1000 or 1500 mg, and pyrimethamine, 50 or 75 mg, given to 72 acute falciparum malaria patients resulted in a 100% cure rate with nil or mild side effects, and no recrudescence of asexual parasite over 4-week follow-up. Preliminary experiments on the drug effect on sporogony showed that the drug combination at the dose used could not completely interrupt the sporozoite formation although many retarded oocysts were found.

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.

Comparative drug trial of a sulfadoxine/pyrimethamine and a sulfalene/pyrimethamine combination against Plasmodium falciparum infections in semi-immune populations of Burma.

The antiplasmodial effect of a single dose treatment with a sulfadoxine/pyrimethamine combination as compared to a sulfalene/pyrimethamine combination against falciparum malaria was assessed in semi-immune populations in Burma in early 1980. Parasite clearance rates on Day 7 after treatment were 99.2% for the sulfadoxine/pyrimethamine combination and 98.6% for the sulfalene/pyrimethamine combination for all age-groups. The earlier recrudescence rates within one month were 3.7% and 9.2% respectively, while the later recrudescence rates between 1 and 2 months were 9% and 8.3% respectively. Hence, both combinations were equally effective for treatment of falciparum malaria as no significant difference in the parasite clearance rates was observed. However, the earlier recrudescence rates showed a significant difference with a higher rate for the sulfalene/pyrimethamine combination. This is thought to be due to the shorter half-life of sulfalene compared to sulfadoxine and to its being unable therefore to suppress the falciparum infections for as long a period as sulfadoxine. But there was not much difference in the later recrudescence rates. These combinations have a stimulating effect on the production of falciparum gametocytes; and, in order to minimize transmission, an effective gametocytocide such as primaquine should be given along with them, as well as with the chloroquine/pyrimethamine combination, in areas with efficient malaria vectors. Recrudescence rates and gametocyte rates were highest among children in the 1-4 years age-group and this could be attributed to their lower level of acquired immunity compared to the older children and adults. Vivax malaria was also found to be effectively suppressed for about 4 weeks with both combinations.(ABSTRACT TRUNCATED AT 400 WORDS)

Malaria en Ninos: Discusion de Algunos Aspectos Clinicos: Diagnosticos y Terapeuticos / Malaria in Children: Discusion of Some Clinical, Diagnostic and Therapeutic Aspects

Se describen 3 casos de malaria en ninos incluyendo el diagnostico y tratamiento, la evolucion y las complicaciones. El primer caso corresponde a una lactante menor con un avanzado estado de desnutricion y una infeccion post-transfusional por Plasmodium Vivax. La respuesta a la cloroquina no fue adecuada requiriendo 2 ciclos adicionales para eliminar los parasitos circulantes. El segundo caso describe un neonato de 25 dias de edad con una infeccion por Plasmodium vivax cuyo mecanismo de transmision natural. La madre fue positiva para Plasmodium Vivax durante el embarazo y puerperio. El paciente presento ademas una metahemoglobinemia como complicacion del tratamiento con primaquina. Finalmente se presenta el caso de un escolar con una malaria por Plasmodium Falciparum resistente a la cloroquina tratada en forma inadecuada con 4 esquemas terapeuticos diferentes, que incluyen quinina intravenosa, trimetoprim-sulfametoxazol y sulfadoxina-pirimetamina

Treatment of quinine resistant falciparum malaria in Thai children.

A study was carried out to assess the efficacy of a modified 7 day course of quinine in children with falciparum malaria, in comparison with those of a 7 day course of quinine at standard dosage and a combination of a 7 day course of quinine and sulfadoxine-pyrimethamine, and in relation to the MIC, and to the serum levels of quinine during the course of treatment. Seventy seven children aged 2 years to 12 years with falciparum malaria were randomly treated with one of the 3 regimens. Group I, quinine 10 mg base per kg body wt. 8 hourly for 7 days, 21 of 28 cases (75%) were cured, while 6 cases (21%) showed RI and 1 case (4%) RII failure. Group II, quinine 10 mg base per kg body wt. 8 hourly for the first 4 days then 15 mg base per kg body wt. 8 hourly for the next 3 days, 20 of 23 cases (87%) were cured, while 3 cases (13%) showed RI failure. Group III, quinine 10 mg base per kg body wt. 8 hourly for 7 days and then sulfadoxine 30 mg per kg body wt. and pyrimethamine 1.5 mg per kg body wt., 16 of 26 cases (62%) were cured and 10 cases (38%) showed RI failure. The cure rates in the 3 groups were not statistically different. The three groups had similar serum quinine concentration profiles. Treatment with quinine was successful in cases in which serum quinine levels could be maintained above MIC for 7 days. There was no additional effect of sulfadoxine-pyrimethamine on quinine.