In 2018 Pakistan initiated its national antimicrobial resistance (AMR) surveillance aligned with Global Antimicrobial Surveillance System (GLASS). To complement this surveillance, we conducted a ...situational analysis of AMR rates among GLASS organisms in the country. Data from published studies and from antibiograms was compared and role of antibiograms as potential contributors to national AMR surveillance explored.
AMR rates for GLASS specified pathogen/antimicrobials combination from Pakistan were reviewed. Data sources included published studies (2006-2018) providing AMR rates from Pakistan (n = 54) as well as antibiograms (2011-2018) available on the Pakistan Antimicrobial Resistance Network (PARN) website. Resistance rates were categorized as follows: Very low: 0-10%, Low: 11-30%, Moderate: 30-50% and High: > 50%.
Published data from hospital and community/laboratory-based studies report resistance rates of > 50% and 30-50% respectively to 3rd generation cephalosporins, fluoroquinolones and cotrimoxazole amongst Klebsiella pneumoniae and Escherichia coli. Carbapenem resistance rates amongst these organisms remained below 30%. High (> 50%) resistance was reported in Acinetobacter species to aminoglycosides and carbapenems among hospitalized patients. The evolution of ceftriaxone resistant Salmonella Typhi and Shigella species is reported. The data showed > 50% to fluoroquinolones amongst Neisseria gonorrhoeae and the spread of methicillin resistant Staphylococcus aureus (< 30%; 2008) to (> 50%; 2010) in hospital settings. Resistance reported in published studies aligned well with antibiogram data. The latter also captured a clear picture of evolution of resistance over the study period.
Both published studies as well antibiograms suggest high rates of AMR in Pakistan. Antibiogram data demonstrating steady increase in AMR highlight its potential role towards supplementing national AMR surveillance efforts particularly in settings where reach of national surveillance may be limited.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Despite high mortality and morbidity, drug-resistant bacterial infections remain the forgotten pandemic. We argue for strengthening of diagnostics, WASH (water, sanitation, and hygiene) and infection ...prevention and control to reduce drug-resistant infections, as an integral part of sustainable high-quality health services, particularly in low- and middle-income countries.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We evaluated Salmonella enterica serotype Typhi strains isolated from all body sites in Pakistan during 2013-2018. Despite an increase in overall number of localized, extensively drug-resistant ...Salmonella Typhi in organ infections during 2018, there was no increase in the proportion of such isolates in comparison with non-extensively drug-resistant isolates.
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•Citrus limetta peel is an effective cheap adsorbent the removal of methylene blue dye.•Adsorption of methylene blue on to citrus limetta peel is spontaneous and endothermic.•The adsorption is best ...represented by Langmuir adsorption isotherm.•The adsorption follows pseudo-second order kinetic model.
In the present work, the potential of citrus limetta peel (CLP) as a low cost adsorbent for the removal of Methylene blue (MB) dye was investigated. Batch adsorption studies were conducted to find out how adsorption was affected by various factors like contact time, initial dye concentration, adsorbent dosage, pH and temperature. The experimental data was analysed in the light of Langmuir, Freundlich and Temkin isotherm models. The data was found to be best represented by Langmuir adsorption isotherm with maximum adsorption capacity for monolayer coverage was found to be 227.3mg/g. The data were analysed in the light of different available kinetic models and was observed to be best followed pseudo-second order kinetics.
Desorption of MB-loaded CLP was studied with various desorbing agents and HCl was found to be most effective desorbing agent among HCl, NaOH, NaCl, CH3COOH and deionised doubly distilled water (DDDW). Results suggest that CLP is a very effective low cost adsorbent for the removal of dyes from wastewater.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Highlights • Fluoroquinolones (FQs) are essential anti-tuberculosis drugs, and regimens containing FQs are increasingly explored and are effective. • FQ resistance among Mycobacterium tuberculosis ...complex isolates is increasing in high-burden countries. • High-burden countries also have weak healthcare systems, which help propagate FQ resistance through omission of regulatory policies and commission of irresponsible drug use. • Drug regulatory agencies as well as other healthcare policymakers and stakeholders must ensure responsible use of FQs to counter increasing drug resistance. • One Health Initiative models work best in preventing FQ misuse in the non-healthcare environment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Mutations in the Rv0678, pepQ and atpE genes of Mycobacterium tuberculosis (MTB) have been reported to be associated with reduced antimycobacterial susceptibility to bedaquiline (BDQ). Resistance ...conferring mutations in treatment naïve MTB strains is likely to have implications for BDQ based new drug regimen that aim to shorten treatment duration. We therefore investigated the genetic basis of resistance to BDQ in MTB clinical isolates from BDQ naïve TB patients from Pakistan. In addition, mutations in genes associated with efflux pumps were investigated as an alternate mechanism of resistance.
Based on convenience sampling, we studied 48 MTB clinical isolates from BDQ naïve TB patients. These isolates (from our strain bank) included 38 MDR/pre-XDR/XDR (10 BDQ resistant, 8 BDQ intermediate and 20 BDQ susceptible) and 10 pan drug susceptible MTB isolates. All strains were subjected to whole genome sequencing and genomes were analysed to identify variants in Rv0678, pepQ, atpE, Rv1979c, mmpLS and mmpL5 and drug resistance associated efflux pump genes.
Of the BDQ resistant and intermediate strains 44% (8/18) had variants in Rv0678 including; two reported mutations S63R/G, six previously unreported variants; L40F, R50Q and R107C and three frameshift mutations; G25fs, D64fs and D109fs. Variants in efflux pumps; Rv1273c (G462K), Rv0507c (R426H) and Rv1634c (E198R) were found to be present in drug resistant isolates including BDQ resistant and intermediate isolates. E198R in efflux pump gene Rv1634c was the most frequently occurring variant in BDQ resistant and intermediate isolates (n = 10).
We found RAVs in Rv0678 to be commonly associated with BDQ resistance. Further confirmation of the role of variants in efflux pump genes in resistance is required so that they may be incorporated in genome-based diagnostics for drug resistant MTB.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary Background Parenteral antibiotic therapy for young infants (aged 0–59 days) with suspected sepsis is sometimes not available or feasible in countries with high neonatal mortality. Outpatient ...treatment could save lives in such settings. We aimed to assess the equivalence of two simplified antibiotic regimens, comprising fewer injections and oral rather than parenteral administration, compared with a reference treatment for young infants with clinical severe infection. Methods We undertook the Simplified Antibiotic Therapy Trial (SATT), a three-arm, randomised, open-label, equivalence trial in five communities in Karachi, Pakistan. We enrolled young infants (aged 0–59 days) who either presented at a primary health-care clinic or were identified by a community health worker with signs of clinical severe infection. We included infants who were not critically ill and whose family refused admission. We randomly assigned infants to either intramuscular procaine benzylpenicillin and gentamicin once a day for 7 days (reference); oral amoxicillin twice daily and intramuscular gentamicin once a day for 7 days; or intramuscular procaine benzylpenicillin and gentamicin once a day for 2 days followed by oral amoxicillin twice daily for 5 days. The primary outcome was treatment failure within 7 days of enrolment and the primary analysis was per protocol. We judged experimental treatments as efficacious as the reference if the upper bound of the 95% CI for the difference in treatment failure was less than 5·0. This trial is registered at ClinicalTrials.gov , number NCT01027429. Findings Between Jan 1, 2010, and Dec 26, 2013, 2780 infants were deemed eligible for the trial, of whom 2453 (88%) were enrolled. Because of inadequate clinical follow-up or treatment adherence, 2251 infants were included in the per-protocol analysis. 820 infants (747 per protocol) were assigned the reference treatment of procaine benzylpenicillin and gentamicin, 816 (751 per protocol) were allocated amoxicillin and gentamicin, and 817 (753 per protocol) were assigned procaine benzylpenicillin, gentamicin, and amoxicillin. Treatment failure within 7 days of enrolment was reported in 90 (12%) infants who received procaine benzylpenicillin and gentamicin (reference), 76 (10%) of those given amoxicillin and gentamicin (risk difference with reference −1·9, 95% CI −5·1 to 1·3), and 99 (13%) of those treated with procaine benzylpenicillin, gentamicin, and amoxicillin (risk difference with reference 1·1, −2·3 to 4·5). Interpretation Two simplified antibiotic regimens requiring fewer injections are equivalent to a reference treatment for young infants with signs of clinical severe infection but without signs of critical illness. The use of these simplified regimens has the potential to increase access to treatment for sick young infants who cannot be referred to hospital. Funding The Saving Newborn Lives initiative of Save the Children, through support from the Bill & Melinda Gates, and by WHO and USAID.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•OPAT serves to avert inpatient costs of IV antimicrobial therapy for complicated urinary tract infections (UTIs).•OPAT outcomes for UTI are poorer in patients with urolithiasis and those ...hospitalized immediately before OPAT induction.•Prospective studies and service evaluations of OPAT for UTI treatment are needed to corroborate these findings.
Outpatient parenteral antimicrobial therapy (OPAT) is widely used to safely administer intravenous antibiotics in the outpatient setting. However, there are risks of treatment failure and clinical complications. We evaluate the outcomes of episodes of urinary tract infection (UTI) treated through OPAT at a large tertiary referral center in the UK.
We retrospectively reviewed patient records of episodes of UTI treated for ≥ 2 days at the Sheffield Teaching Hospitals OPAT unit from 2017 to 2021. We defined OPAT and infection failure as unplanned 30-day hospital readmissions and symptomatic non-improvement, respectively. Univariate and multivariate logistic regression analyses were performed to analyze predictors of these outcomes.
162 episodes of UTI in 115 patients were analyzed. OPAT failure was observed in 16.0 % (n = 26) of episodes, while infection remained unresolved in 8.0 % (n = 13) of episodes. Urolithiasis was an independent risk factor of both OPAT (odds ratio OR, 4.3; 95 % confidence interval CI, 1.2–16.1; p = 0.03) and infection failure (OR, 5.9; 95 % CI, 1.2–29.9; p = 0.03). Prior hospitalization also increased the risk of both OPAT (OR, 4.4; 95 % CI, 1.1–18.7; p = 0.04) and infection failure (OR, 8.0, 95 % CI, 1.3–78.4; p = 0.04).
These results can assist clinicians at commencement of OPAT to identify patients at high risk of treatment failure. Wider network studies are required to further elicit the role of urolithiasis and its treatment to improve outcomes of UTI management in OPAT.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
IntroductionIn settings where the private sector constitutes a larger part of the health system, profit-gathering can take primacy over patients’ well-being. In their interactions with pharmaceutical ...companies, private general practitioners (GPs) can experience the conflict of interest (COI), a situation whereby the impartiality of GPs’ professional decision making may be influenced by secondary interests such as financial gains from prescribing specific pharmaceutical brands.Methods and analysisThis study is a randomised controlled trial to assess the impact of a multifaceted intervention on GPs’ medical practice. The study sample consists of 419 registered GPs who own/work in private clinics and will be randomly assigned to intervention and control groups. The intervention group GPs will be exposed to emotive and educational seminars on medical ethics, whereas control group GPs will be given seminars on general medical topics. The primary outcome measure will be GPs’ prescribing practices, whereas the secondary outcome measures will be their knowledge and attitudes regarding COI that arises from pharmaceutical incentivisation. In addition to a novel standardised pharmaceutical representatives (SPSR) method, in which field researchers will simulate pharmaceutical marketing with GPs, presurvey and postsurvey, and qualitative interviewing will be performed to collect data on GPs’ knowledge, attitudes and practices in relation to COI linked with pharmaceutical incentives. Univariate and multivariate statistical analyses will be performed to measure a change in GPs’ knowledge, attitudes and practices, while qualitative analysis will add to our understanding of the quantitative SPSR data.Ethics and disseminationEthics approval has been obtained from the Pakistan National Bioethics Committee (# 4-87/NBC-582/21/1364), the Aga Khan University (# 2020-4759-1129) and the London School of Hygiene and Tropical Medicine (# 26506). We will release results within 6–9 months of the study’s completion.Trial registration numberISRCTN12294839.
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