High multidrug resistance in urinary tract infections in a tertiary hospital, Kathmandu, Nepal.

SETTING: Tribhuvan University Teaching Tertiary Care Hospital, Kathmandu, Nepal, May-October 2019. OBJECTIVE: 1) To describe the bacteriological profile, 2) to identify the antimicrobial resistance (AMR) pattern, and 3) to find the demographic characteristics associated with the presence of bacterial growth and multidrug resistance (MDR) in adult urine samples undergoing culture and drug susceptibility testing. DESIGN: This was a hospital-based, cross-sectional study using routine laboratory records. RESULTS: Among 11,776 urine samples, 16% (1,865/11,776) were culture-positive, predominantly caused by Escherichia coli (1,159/1,865; 62%). We found a high prevalence of resistance to at least one antibiotic (1,573/1,865; 84%) and MDR (1,000/1,865; 54%). Resistance to commonly used antibiotics for urinary tract infections (UTIs) such as ceftazidime, levofloxacin, cefepime and ampicillin was high. Patients aged ⩾60 years (adjusted prevalence ratio [aPR] 1.6, 95% CI 1.4-1.7) were more likely to have culture positivity. Patients with age ⩾45 years (45-59 years: aPR 1.5, 95% CI 1.3-1.7; ⩾60 years: aPR 1.4, 95% CI 1.2-1.6), male sex (aPR 1.3, 95% CI 1.2-1.5) and from inpatient settings (aPR 1.4, 95% CI 1.2-1.7) had significantly higher prevalence of MDR. CONCLUSION: Urine samples from a tertiary hospital showed high prevalence of E. coli and MDR to routinely used antibiotics, especially among inpatients. Regular surveillance and application of updated antibiograms are crucial to monitor the AMR situation in Nepal.

LIEU: Hôpital universitaire de soins tertiaires de Tribhuvan, Katmandu, Népal, mai­octobre 2019. OBJECTIF: 1) Décrire le profil bactériologique, 2) identifier le profil de résistance antimicrobienne (AMR), et 3) identifier les caractéristiques démographiques associées à la présence de croissance bactérienne et de résistance à plusieurs médicaments (MDR) dans les échantillons urinaires d'adultes mis en culture et testés pour sensibilité aux médicaments. MÉTHODE: Il s'agissait d'une étude transversale hospitalière réalisée en utilisant les dossiers de laboratoire de routine. RÉSULTATS: Parmi 11 776 échantillons urinaires, 16% (1 865/11 776) étaient positifs par culture, principalement à Escherichia coli (1 159/1 865 ; 62%). Nous avons observé une prévalence élevée de résistance à au moins un antibiotique (1 573/1 865 ; 84%) et de MDR (1 000/1 865 ; 54%). La résistance aux antibiotiques fréquemment utilisés dans le traitement des infections urinaires (UTI), comme la ceftazidime, la lévofloxacine, la céfépime et l'ampicilline était élevée. Les patients âgés ⩾ 60 ans (ratio de prévalence ajusté [aPR] 1,6 ; IC 95% 1,4­1,7) étaient plus susceptibles d'avoir une culture positive. Les patients âgés de ⩾ 45 ans (45­59 ans : aPR 1,5 ; IC 95% 1,3­1,7 ; ⩾ 60 ans : aPR 1,4 ; IC 95% 1,2­1,6), les hommes (aPR 1,3 ; IC 95% 1,2­1,5) et les patients hospitalisés (aPR 1,4 ; IC 95% 1,2­1,7) avaient une prévalence significativement plus élevée de MDR. CONCLUSION: Les échantillons urinaires d'un hôpital tertiaire étaient associés à une prévalence élevée d'E. coli et de MDR aux antibiotiques utilisés en routine, notamment chez les patients hospitalisés. Une surveillance régulière et l'utilisation d'antibiogrammes à jour sont essentielles au suivi de l'AMR au Népal.

Interleukin-17 promotes prostate cancer via MMP7-induced epithelial-to-mesenchymal transition.

Chronic inflammation has been associated with a variety of human cancers including prostate cancer. Interleukin-17 (IL-17) is a critical pro-inflammatory cytokine, which has been demonstrated to promote development of prostate cancer, colon cancer, skin cancer, breast cancer, lung cancer and pancreas cancer. IL-17 promotes prostate adenocarcinoma with a concurrent increase of matrix metalloproteinase 7 (MMP7) expression in mouse prostate. Whether MMP7 mediates IL-17's action and the underlying mechanisms remain unknown. We generated Mmp7 and Pten double knockout (KO) (Mmp7-/-) mouse model and demonstrated that MMP7 promotes prostate adenocarcinoma through induction of epithelial-to-mesenchymal transition (EMT) in Pten-null mice. MMP7 disrupted E-cadherin/ß-catenin complex to upregulate EMT transcription factors in mouse prostate tumors. IL-17 receptor C and Pten double KO mice recapitulated the weak EMT characteristics observed in Mmp7-/- mice. IL-17 induced MMP7 and EMT in human prostate cancer LNCaP, C4-2B and PC-3 cell lines, while small interfering RNA knockdown of MMP7 inhibited IL-17-induced EMT. Compound III, a selective MMP7 inhibitor, decreased development of invasive prostate cancer in Pten single KO mice. In human normal prostates and prostate tumors, IL-17 mRNA levels were positively correlated with MMP7 mRNA levels. These findings demonstrate that MMP7 mediates IL-17's function in promoting prostate carcinogenesis through induction of EMT, indicating IL-17-MMP7-EMT axis as a potential target for developing new strategies in the prevention and treatment of prostate cancer.

Inadequate Empirical Antibiotic Therapy in Hospital Acquired Pneumonia.

INTRODUCTION: Inadequate empirical antibiotic therapy for HAP is a common phenomena and one of the indicators of the poor stewardship. This study intended to analyze the efficacy of empirical antibiotics in the light of microbiological data in HAP cases. METHODS: Suspected cases of HAP were followed for clinico-bacterial evidence, antimicrobial resistance and pre and post culture antibiotic use. The study was taken from February,2014 to July 2014 in department of Microbiology and department of Respiratory medicine prospectively. Data was analyzed by Microsoft Office Excel 2007. RESULTS: Out of 758 cases investigated, 77(10 %) cases were HAP, 65(84%) of them were culture positive and 48(74 %) were late in onset. In early onset cases, isolates were Acinetobacter 10(42%), Escherichia coli 5(21%), S.aureus 4(17%), Klebsiella 1(4%) and Pseudomonas 1(4%). From the late onset cases Acinetobacter 15(28%), Klebsiella 17(32%) and Pseudomonas 13(24%) were isolated. All Acinetobacter, 78% Klebsiella and 36% Pseudomonas isolates were multi drug resistant. Empirical therapies were inadequate in 12(70%) of early onset cases and 44(92%) of late onset type. Cephalosporins were used in 7(41%) of early onset infections but found to be adequate only in 2(12%) cases. Polymyxins were avoided empirically but after cultures were used in 9(19%) cases. CONCLUSIONS: Empirical antibiotics were vastly inadequate, more frequently so in late onset infections. Use of cephalosporins empirically in early onset infections and avoiding empirical use of polymyxin antibiotics in late onset infections contributed largely to the findings. Inadequate empirical regimen is a real time feedback for a practitioner to update his knowledge on the local microbiological trends.

Bacterial etiology of acute diarrhea in children under five years of age.

BACKGROUND: Diarrheal diseases are major problem of developing countries. Though precise data on childhood mortality associated with diarrheal diseases in Nepal is not available, it has been estimated that approximately 25% of child death are associated with diarrheal disease, particularly acute diarrhea. The purpose of this study was to assess the incidence of bacterial pathogens causing acute diarrhea in children under 5 years of age. METHODS: A total of 525 children with acute diarrhea in a children's hospital of Kathmandu, Nepal were enrolled between April 2011 to September 2011. Feacal specimens for culture were inoculated to the several media. The organisms were identified by different biochemical tests and serotyping. Their antibiotic sensitivity tests were performed by Kirby-Bauer's disc diffusion method as recommended by CLSI. RESULTS: Out of total 525 enrolled cases bacterial infection was found to be 46 (8.8%). Bacterial infection was found to be of highest, 36 (78.3%) in the age group between 6-24 months. Among the total enrolled cases the prevalence of Shigella species was 24 (4.6%) followed by Escherichia coli 12 (2.3%) and Salmonella species 10 (1.9%). Chloramphenicol and Tetracycline showed efficacy in 9 (90.0%) isolates of Salmonella species, Gentamycin showed efficacy in 22 (91.7%) isolates of Shigella species and Chloramphenicol showed 100% efficacy against Escherichia coli whereas 7 (70.0%) isolates of Salmonella species were resistant to ampicillin in vitro. MDR was highest 7 (70.0%) in Salmonella species. CONCLUSIONS: The bacterial pathogens were found to be a significant cause of acute diarrhea. The most common causative organism for acute diarrhea were Shigella spp. Awareness of improving hygiene and infectious diseases may reduce the burden of infection.

Estimation of serum uric acid in cases of hyperuricaemia and gout.

INTRODUCTION: Gout is crystal deposit arthritis and is an ancient disease. The biologic precursor to gout is hyperuricaemia. The prevalence of hyperuricaemia and gout has an increasing trend all over the world including the developing countries. The purpose of this study is to estimate serum uric acid level in hyperuricaemic and gout patients attending a medical college hospital. METHODS: A consecutive 150 hyperuricaemics and 150 gout patients attending Tribhuwan University Teaching Hospital from June to September 2007 were included in this study. The serum uric acid level was measured by the enzymatic (PAP- Uricase) method. The patients with acute gout were interviewed and relevant information was obtained. RESULTS: Males comprised 84% of gout cases. Hyperuricaemia was common in both sexes. The mean age for gout was 47.49 and 56.65 years in males and females respectively. The mean age for the first gout attack was 42.1 +/- 14.0 years. Family history was positive in 22% of cases. The overall mean serum uric acid level in hyperuricaemics was 7.2 +/- 0.7 mg/dL and 8.4 +/- 1.1 mg/dL in acute gout (p 0.0001). The mean serum uric acid level was significantly (p 0.0001) high among males both at the asymptomatic phase and at acute gout. Gout was more common in non-vegetarians (95%) and alcoholics (65.3%). Serum uric acid level was inversely related with the amount of daily water intake (p 0.0001). CONCLUSIONS: Serum uric acid level is significantly high among the male gouty arthritic patients. However, it is also high among asymptomatic hyperuricaemic cases of both sexes.

Epidemiology of malaria in two Eastern districts of Nepal.

BACKGROUNDS: Malaria is one of the major public health problems in Southeast Asia including Nepal having relatively high burden of malaria. Jhapa and Morang districts are malaria endemic plain area of South-eastern part of Nepal. OBJECTIVES: The evaluate the recent epidemiology of malaria situation in Jhapa and Morang districts, which are the districts in eastern Nepal with high transmission of malaria and to assess the knowledge, attitudes and practices of the people in prevention and treatment for malaria infection. MATERIALS AND METHODS: This descriptive cross-sectional study was carried out with volunteer participation of suspected malaria patients seeking care at the government of Nepal managed primary health care centres located in 2 malaria endemic districts in eastern Nepal. Conventional Giemsa stained thick and thin blood smears prepared from finger prick blood were examined following standard protocols. Suspected patients'/attendants' knowledge on malaria, disease symptoms, prevention and control measures were assessed using a structured questionnaire. Chi square and Fisher exact test were used for statistical analysis of the data. RESULTS: Among the total 199 malaria suspected cases studied, 32 (16.1%) cases were confirmed by microscopic findings; where, P. vivax was 12.6% (25/199) and P. falciparum in only 3.1% (6/199). The highest numbers of cases were in age group 20-29 years. Among the total positive cases 75% were male and 37.5% were labourers in occupation. Among the total cases, 32 had provided the history of recent travel to malaria endemic area in India, among them 43.8% (P<0.001) were found to be infected with the malarial parasites (P<0.001). Among the total cases, 69.7% showed some knowledge of malaria, among which fever was the most common symptom mentioned by 68.3%. Occupation (P<0.001) and education (P<0.001) were found significantly associated with the knowledge on mode of transmission. CONCLUSION: Jhapa district showed higher SPR than Morang, which indicated that Jhapa may be more malaria affected than Morang. Knowledge on malaria transmission and preventive measures are still lacking in deep villages, in spite of different efforts of the government. To improve the malaria morbidity in the districts, health education of the most marginalized people through audio visual methods may be beneficial.

Comparative evaluation of microscopy and polymerase chain reaction (PCR) for the diagnosis in suspected malaria patients of Nepal.

Microscopy has been the most common technique for the diagnosis of malaria in Nepal. This study was undertaken at CDM, TU, Kathmandu, and Department of Clinical Tropical Medicine, Mahidol University, Bangkok to compare the efficiency of microscopy and PCR for malaria diagnosis in Nepalese context. During July-August 2007, blood samples were collected in glass slides and on filter papers from suspected malaria cases of Kanchanpur, Jhapa and Morang Districts. Sample transportation and storage was done using standard protocol. Microscopy was done at the heath posts in the district in Nepal while Nested PCR using previously standardized primers was carried out at Mahidol University. Among 824 malaria suspected cases, 19.2% (157) were laboratory confirmed as malaria cases (P. vivax 10.9%, P. falciparium 7.7% and 0.4% were of mixed infection) by microscopy. The parasite count range was detected as 320-25020 parasites/microl. Among total 132 samples (114 microscopic positive, 18 negative) were processed for nested PCR. Among microscopic positive samples with increase of the parasitaemia/microl of the blood, the rate of detection by PCR (75.4%) was increased though the PCR failed to detect 2 cases having the parasitaemia 5000-15000/microl of blood however 4 microscopic negative cases were detected as P. vivax infection. Among the microscopy positive samples for P. falciparum, 3 were found P. vivax and 2 were found as mixed infection of Pv and Pf and 6 P. vivax were found positive for P. falciparum by PCR. Two microscopy positive samples for mixed infection were found be positive for one Pv and one Pf by PCR. PCR could be good tool in confirming the clinically strongly suspected but microscopically negative malaria cases and advanced molecular epidemiological studies, although its use in routine diagnosis may not be feasible.

Gender variations in the prevalence of parasitic infections and the level of awareness in adolescents in rural Nepal.

The study was conducted in rural school adolescent children to investigate the awareness and its association in parasitic infections in boys and girls. Of the 182 children examined 119 (65.3%) were male and 63 (34.6%) were female, age ranged 12-20 years with median age 15 years. Out of 182 stool samples examined 73 (40%) were found to be positive for parasites in which two or more parasites were found in 10 stool samples. Giardia lamblia 33 (18.1%) was the predominant parasite followed by hook worm 27 (14.8%) Entamoeba histolytica 13 (7.1%), Ascaris lumbricoides 05 (2.7%), Hyminolepis nana 02 (2.2%) and Trichuris trichiuria 01 (0.5%). Thirty-one (49.2%) in 63 females and 40 (33.6%) of the 119 males were positive for parasitic infections. The prevalence of worm infection was significantly higher in female children than male (p < or = 0.05). In contrast to the high parasitic prevalence rate in females they possessed significantly higher levels of awareness about parasitic infections. Out of 119 males 99 (83.2%) and 61 (96.8%) of the 63 females (p < or = 0.05) knew that worms suck food from host body. Similarly, 62.2% of males and 96.85 of females (p < or = 0.05) knew that parasites suck blood from human body. More study should be carried out to find out the gender difference in parasitic infection and level of exposure to risk factors.