OBJECTIVE: To check the prices, availability, and affordability of the World Health Organization (WHO) key access antibiotics in private sector pharmacies of Lahore, Pakistan.
METHODOLOGY: A survey of WHO key access antibiotics from WHO essential medicine list 2017 was conducted in private sector pharmacies of 4 different regions of Lahore employing adapted WHO/HAI methodology. The comparison of prices and availability between originator brands (OB) and lowest price generics (LPG) were conducted followed by the effect of medicine price differences on patient's affordability. The data were analyzed using a preprogrammed WHO Microsoft excel workbook.
RESULTS: The mean availability of OB products was 45.20% and the availability of LPGs was 40.40%. The OBs of co-amoxiclav, clarithromycin and metronidazole and LPGs of azithromycin and ciprofloxacin were easily available (100%) in all private sector pharmacies. Whereas, antibiotics like chloramphenicol, cloxacillin, nitrofurantoin, spectinomycin, and cefazolin were totally unavailable in all the surveyed pharmacies. The OBs and LPGs with high MPRs were ceftriaxone (OB; 15.31, LPG; 6.38) and ciprofloxacin (OB; 12.42, LPG; 5.77). The median of brand premium obtained was 38.7%, which varied between the lowest brand premium of 3.97% for metronidazole and highest for ceftriaxone i.e. 140%. The cost of standard treatment was 0.5 day's wage (median) if using OB and 0.4 day's wage (median) for LPG, for a lowest paid unskilled government worker. Treatment with OB and LPG was unaffordable for ciprofloxacin (OB; 2.4, LPG; 1.1) & cefotaxime (OB; 12.7, LPG; 8.1).
CONCLUSION: There is dire need to properly implement price control policies to better regulate fragile antibiotic supply system so that the availability of both OB and LPG of key access antibiotics should be increased. The prices could be reduced by improving purchasing efficiency, excluding taxes and regulating mark-ups. This could increase the affordability of patients to complete their antibiotic therapy with subsequent reduction in antimicrobial resistance.
Aim: This study was designed to determine whether the phenotypic antibiotic resistance pattern of B. pseudomallei is associated with the source of isolates and the genotype.
Materials and Methods: A collection of 111 B. pseudomallei isolates from veterinary cases of melioidosis and the environments (soil and water) were obtained from stock cultures of previous studies and were phylogenetically characterized by multilocus sequence typing (ST). The susceptibility to five antibiotics, namely meropenem (MEM), imipenem, ceftazidime (CAZ), cotrimoxazole (SXT), and co-amoxiclav (AMC), recommended in both acute and eradication phases of melioidosis treatment were tested using minimum inhibitory concentration antibiotics susceptibility test.
Results: Majority of isolates were susceptible to all antibiotics tested while few resistant strains to MEM, SXT, CAZ, and AMC were observed. Statistically significant association was found between resistance to MEM and the veterinary clinical isolates (p<0.05). The likelihood of resistance to MEM was significantly higher among the novel ST 1130 isolates found in veterinary cases as compared to others.
Conclusion: The resistance to MEM and SXT appeared to be higher among veterinary isolates, and the novel ST 1130 was more likely to be resistant to MEM as compared to others.
OBJECTIVE: The purpose of this study was to investigate the influence of P-gp modulation on the efficacy of treatment regimen.
METHOD: P-gp modulation in rats was performed by using P-gp inducer (150 mg/kg rifampicin) and P-gp inhibitor (10 mg/kg cyclosporine A) for 14 days prior to be infected with Helicobacter pylori (H. pylori). The rats were further divided into groups, which were normal control, vehicle control, antibiotics and omeprazole, antibiotics only and omeprazole only for another 2 weeks of treatment. The ulcer formation and P-gp expression were determined by using macroscopic evaluation and western blot analysis, respectively.
RESULTS: The highest P-gp expression was shown in the induced P-gp rats (2.00 ± 0.68) while the lowest P-gp expression was shown in the inhibited P-gp rats (0.45 ± 0.36) compared to the normal P-gp rats. In all groups, the rats which were infected with H. pylori, had a significant increase (p amoxicillin) and proton pump inhibitor (omeprazole) have shown to effectively eradicate the H. pylori infection. Thus, P-gp expression influenced the effectiveness of the treatment.
METHODS: The structures of all synthesized compounds were characterized by physicochemical properties and spectral means (IR and NMR). The synthesized compounds were evaluated for their in vitro antimicrobial activity against Gram-positive (B. subtilis), Gram-negative (P. aeruginosa and E. coli) bacterial and fungal (C. albicans and A. niger) strains by tube dilution method using ciprofloxacin, amoxicillin and fluconazole as standards. In-vitro antioxidant and anti-urease screening was done by DPPH assay and indophenol method, respectively. The in-vitro anticancer evaluation was carried out against MCF-7 and HCT116 cancer cell lines using 5-FU as standards.
RESULTS, DISCUSSION AND CONCLUSION: The biological screening results reveal that the compounds T5 (MICBS, EC = 24.7 µM, MICPA, CA = 12.3 µM) and T17 (MICAN = 27.1 µM) exhibited potent antimicrobial activity as comparable to standards ciprofloxacin, amoxicillin (MICCipro = 18.1 µM, MICAmo = 17.1 µM) and fluconazole (MICFlu = 20.4 µM), respectively. The antioxidant evaluation showed that compounds T2 (IC50 = 34.83 µg/ml) and T3 (IC50 = 34.38 µg/ml) showed significant antioxidant activity and comparable to ascorbic acid (IC50 = 35.44 µg/ml). Compounds T3 (IC50 = 54.01 µg/ml) was the most potent urease inhibitor amongst the synthesized compounds and compared to standard thiourea (IC50 = 54.25 µg/ml). The most potent anticancer activity was shown by compounds T2 (IC50 = 3.84 μM) and T7 (IC50 = 3.25 μM) against HCT116 cell lines as compared to standard 5-FU (IC50 = 25.36 μM).
METHODS: H pylori-positive patients were randomly assigned to either a rabeparzole (Pariet) 20 mg b.i.d., amoxicillin (Ospamox) 1 g b.i.d. and clarithromycin (Klacid) 500 mg b.i.d. for 14 days or rabeprazole (Pariet) 20 mg q.i.d., amoxicillin (Ospamox) 1 g q.i.d. also for 14 days. Eradication was tested for by the C13 -UBT at least 4 weeks after the completion of therapy.
RESULTS: H pylori was eradicated in 86.2% of patients (81/94) (95% CI: 77.8-91.7) in the STT group compared with 92.8% (90/97) (95% CI: 85.9-96.5) in the HDDT group on ITT analysis. On PP analysis, H pylori was eradicated in 91.0% of patients (81/89) (95% CI: 83.3-95.4) in the STT group compared with 93.8% (90/96) (95% CI: 87.0-97.1) in the HDDT group. Side effects were few although many patients in the STT arm complained of bitter taste. The HDDT arm was well tolerated by patients.
CONCLUSIONS: The HDDT gave a high eradication rate comparable to the STT for 2 weeks and was a well-tolerated regimen for H pylori eradication.
DESIGN: Prospective study.
PATIENTS AND METHODS: Patients were followed up endoscopically at 3, 6, 12 and 24 months after successful H. pylori eradication and duodenal ulcer healing. H. pylori status was determined by culture, rapid urease test, Gram's stain of a fresh tissue smear and histological examination of antral biopsies and rapid urease test and histological examination of corpus biopsies.
MAIN OUTCOME MEASURES: Duodenal ulcer healing, H. pylori reinfection.
RESULTS: Thirty-eight patients with duodenal ulcer disease (35 active, 3 healed) had successfully eradicated H. pylori following treatment with omeprazole/amoxycillin (n = 11), omeprazole/amoxycillin/metronidazole (n = 16) and colloidal bismuth subcitrate/ amoxycillin/metronidazole (n = 11). All patients with active duodenal ulcer had healed ulcers at the end of therapy. Thirty-five of 38 patients were seen according to schedule up to 2 years; two patients were seen up to 12 months and one up to 6 months only. Reinfection with H. pylori was not recorded in any of our patients. Shallow duodenal ulcers were noted in three patients at 1-year follow-up, two of whom admitted to taking non-steroidal anti-inflammatory drugs (NSAIDs); H. pylori status was negative in all three. Subsequent follow-up revealed spontaneous healing of the ulcers in all three patients. At 2 years, one patient whose H. pylori status was negative had recurrence of duodenal ulcer. All of the three patients who defaulted subsequent to follow-up were negative for H. pylori and had healed ulcers on follow-up endoscopy at 6 and 12 months.
CONCLUSION: Reinfection rate with H. pylori was zero in a group of South-East Asian patients who had successfully eradicated the infection. Duodenal ulcer relapse was also low (2.9%) in this group of patients at 2 years.
MATERIALS AND METHODS: Physicians who managed H. pylori eradication in daily practice across 10 Southeast Asian countries were invited to participate in an online questionnaire, which included questions about the local availability of antimicrobial susceptibility tests (ASTs) and their preferred eradication regimens in real-world practice. An empiric regimen was considered inappropriate if it did not follow the local guidelines/consensus, particularly if it contained antibiotics with a high reported resistance rate or was recommended not to be empirically used worldwide.
RESULTS: There were 564 valid responses, including 314 (55.7%) from gastroenterologists (GIs) and 250 (44.3%) from non-GI physicians. ASTs were unavailable in 41.7%. In countries with low and intermediate clarithromycin resistance, the most common first-line regimen was PAC (proton pump inhibitor [PPI], amoxicillin, clarithromycin) (72.7% and 73.2%, respectively). Regarding second-line therapy, the most common regimen was bismuth-based quadruple therapy, PBMT (PPI, bismuth, metronidazole, tetracycline) (50.0% and 59.8%, respectively), if other regimens were used as first-line treatment. Concomitant therapy (PPI, amoxicillin, clarithromycin, metronidazole) (30.5% and 25.9%, respectively) and PAL (PPI, amoxicillin, levofloxacin) (22.7% and 27.7%, respectively) were favored if PBMT had been used as first-line treatment. In countries with high clarithromycin resistance, the most common first-line regimen was PBMT, but the utilization rate was only 57.7%. Alarmingly, PAC was prescribed in 27.8% of patients, ranking as the second most common regimen, and its prescription rate was higher in non-GI physicians than GI physicians (40.1% vs. 16.2%, p
MATERIALS AND METHODS: In a prospective study with purposive sampling, amoxicillin/clavulanate tablet formulations for canine use were collected in four countries (wholesalers or veterinary practice) and shipped to a central bioanalytical laboratory. Twenty-four samples were collected from the UK (nine), Malaysia (nine), Serbia (four) and Thailand (two), yielding 18 different formulations (10 veterinary). Packaging inspection, tablet disintegration and content assay were conducted (validated high-performance liquid chromatography with ultra-violet detection); content was acceptable when within the 90% to 120% pre-specified range (US Pharmacopeia).
RESULTS: Secondary packaging was present for 13 of 24 samples and primary packaging integrity was verified for all but one sample. Amoxicillin trihydrate/potassium clavulanate label ratio was 4:1, except for three formulations (2:1). Tablet dose strength ranged from 250 to 625 mg. All formulations contained both analytes. For amoxicillin, two of 24 samples were out of specification with 72.8% (Malaysia) and 82.3% (Thailand) of labelled content. For clavulanate, four of 24 samples were out of specification with 46.9% (Serbia), 79.0% (UK), 84.3% (Serbia) and 86.5% (Thailand) of labelled content. One formulation (Thailand) failed for both analytes.
CLINICAL SIGNIFICANCE: Antimicrobial formulations of substandard quality have negative consequences for efficacy in patients and potentially promote antimicrobial resistance. There was evidence of substandard formulations in all countries, not only for amoxicillin but especially for clavulanate; this could compromise equitable access to acceptable quality essential veterinary medicines worldwide.
METHODS: We did a systematic review and meta-analysis of primary antibiotic resistance to H pylori and the efficacy of first-line regimens in the Asia-Pacific region. We searched PubMed, Embase, and the Cochrane Library for articles published between Jan 1, 1990, and Sept 30, 2016; we also searched abstracts from international conferences. Both observational studies and randomised controlled trials were eligible for inclusion in the analysis of primary antibiotic resistance, but only randomised controlled trials were eligible for inclusion in the analysis of efficacy of first-line therapies. Meta-analysis was by the random-effects model to account for the substantial variations in resistance across the region. We did subgroup analyses by country and study period (ie, before 2000, 2001-05, 2006-10, and 2011-15) to establish country-specific prevalences of primary antibiotic resistance and first-line eradication rates. This study is registered with PROSPERO, number CRD42017057905.
FINDINGS: 176 articles from 24 countries were included in our analysis of antibiotic resistance. The overall mean prevalences of primary H pylori resistance were 17% (95% CI 15-18) for clarithromycin, 44% (95% CI 39-48) for metronidazole, 18% (95% CI 15-22) for levofloxacin, 3% (95% CI 2-5) for amoxicillin, and 4% (95% CI 2-5) for tetracycline. Prevalence of resistance to clarithromycin and levofloxacin rose significantly over time during the period investigated, whereas resistance to other antibiotics remained stable. 170 articles from 16 countries were included in analysis of efficacy of first-line therapies. We noted unsatisfactory efficacy (ie, <80%) with clarithromycin-containing regimens in countries where the clarithromycin resistance rates were higher than 20%.
INTERPRETATION: The prevalence of primary antibiotic resistance varied greatly among countries in the Asia-Pacific region, and thus treatment strategy should be adapted relative to country-specific resistance patterns. Clarithromycin-containing regimens should be avoided in countries where the prevalence of clarithromycin resistance is higher than 20%.
FUNDING: Ministry of Health and Welfare of Taiwan, Ministry of Science and Technology of Taiwan, and Amity University.