ResearchPad - antibiotic-resistance https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Substantial improvement of tetraene macrolide production in <i>Streptomyces diastatochromogenes</i> by cumulative drug resistance mutations]]> https://www.researchpad.co/article/elastic_article_7861 Tetraene macrolides remain one of the most reliable fungicidal agents as resistance of fungal pathogens to these antibiotics is relatively rare. The modes of action and biosynthesis of polyene macrolides had been the focus of research over the past few years. However, few studies have been carried out on the overproduction of polyene macrolides. In the present study, cumulative drug-resistance mutation was used to obtain a quintuple mutant G5-59 with huge tetraene macrolide overproduction from the starting strain Streptomyces diastatochromogenes 1628. Through DNA sequence analysis, the mutation points in the genes of rsmG, rpsL and rpoB were identified. Additionally, the growth characteristic and expression level of tetrRI gene (belonging to the large ATP binding regulator of LuxR family) involved in the biosynthesis of tetraene macrolides were analyzed. As examined with 5L fermentor, the quintuple mutant G5-59 grew very well and the maximum productivity of tetramycin A, tetramycin P and tetrin B was as high as 1735, 2811 and 1500 mg/L, which was 8.7-, 16- and 25-fold higher than that of the wild-type strain 1628, respectively. The quintuple mutant G5-59 could be useful for further improvement of tetraene macrolides production at industrial level.

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<![CDATA[Virulence factors and antibiograms of <i>Escherichia coli</i> isolated from diarrheic calves of Egyptian cattle and water buffaloes]]> https://www.researchpad.co/article/elastic_article_8462 Diarrhea caused by Escherichia coli in calves is an important problem in terms of survivability, productivity and treatment costs. In this study, 88 of 150 diarrheic animals tested positive for E. coli. Of these, 54 samples had mixed infection with other bacterial and/or parasitic agents. There are several diarrheagenic E. coli pathotypes including enteropathogenic E. coli (EPEC), Shiga-toxin producing E. coli (STEC), enterotoxigenic E. coli (ETEC) and necrotoxigenic E. coli (NTEC). Molecular detection of virulence factors Stx2, Cdt3, Eae, CNF2, F5, Hly, Stx1, and ST revealed their presence at 39.7, 27.2, 19.3, 15.9, 13.6, 9.0, 3.4, and 3.4 percent, respectively. As many as 13.6% of the isolates lacked virulence genes and none of the isolate had LT or CNF1 toxin gene. The odds of isolating ETEC from male calves was 3.6 times (95% CI: 1.1, 12.4; P value = 0.042) that of female calves, whereas the odds of isolating NTEC from male calves was 72.9% lower (95% CI: 91.3% lower, 15.7% lower; P value = 0.024) than that in females. The odds of isolating STEC in winter was 3.3 times (95% CI: 1.1, 10.3; P value = 0.037) that of spring. Antibiograms showed 48 (54.5%) of the isolates to be multi-drug resistant. The percent resistance to tetracycline, streptomycin, ampicillin, and trimethoprim-sulfamethoxazole was 79.5, 67.0, 54.5, and 43.0, respectively. Ceftazidime (14.8%), amoxicillin-clavulanic acid (13.6%) and aztreonam (11.3%) showed the lowest resistance, and none of the isolates was resistant to imipenem. The results of this study can help improve our understanding of the epidemiological aspects of E. coli infection and to devise strategies for protection against it. The prevalence of E. coli pathotypes can help potential buyers of calves to avoid infected premises. The antibiograms in this study emphasizes the risks associated with the random use of antibiotics.

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<![CDATA[Chitosan-propolis nanoparticle formulation demonstrates anti-bacterial activity against Enterococcus faecalis biofilms]]> https://www.researchpad.co/article/5989db50ab0ee8fa60bdc122

Propolis obtained from bee hives is a natural substance with antimicrobial properties. It is limited by its insolubility in aqueous solutions; hence ethanol and ethyl acetate extracts of Malaysian propolis were prepared. Both the extracts displayed antimicrobial and anti-biofilm properties against Enterococcus faecalis, a common bacterium associated with hospital-acquired infections. High performance liquid chromatography (HPLC) analysis of propolis revealed the presence of flavonoids like kaempferol and pinocembrin. This study investigated the role of propolis developed into nanoparticles with chitosan for its antimicrobial and anti-biofilm properties against E. faecalis. Bacteria that grow in a slimy layer of biofilm are resistant to penetration by antibacterial agents. The use of nanoparticles in medicine has received attention recently due to better bioavailability, enhanced penetrative capacity and improved efficacy. A chitosan-propolis nanoformulation was chosen based on ideal physicochemical properties such as particle size, zeta potential, polydispersity index, encapsulation efficiency and the rate of release of the active ingredients. This formulation inhibited E. faecalis biofilm formation and reduced the number of bacteria in the biofilm by ~90% at 200 μg/ml concentration. When tested on pre-formed biofilms, the formulation reduced bacterial number in the biofilm by ~40% and ~75% at 200 and 300 μg/ml, respectively. The formulation not only reduced bacterial numbers, but also physically disrupted the biofilm structure as observed by scanning electron microscopy. Treatment of biofilms with chitosan-propolis nanoparticles altered the expression of biofilm-associated genes in E. faecalis. The results of this study revealed that chitosan-propolis nanoformulation can be deemed as a potential anti-biofilm agent in resisting infections involving biofilm formation like chronic wounds and surgical site infections.

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<![CDATA[Nosocomial transmission of extensively drug resistant Acinetobacter baumannii strains in a tertiary level hospital]]> https://www.researchpad.co/article/N9f3b656c-39ce-49ef-bced-db8369f1110d

Acinetobacter baumannii is an opportunistic infectious agent that affects primarily immunocompromised individuals. A. baumannii is highly prevalent in hospital settings being commonly associated with nosocomial transmission and drug resistance. Here, we report the identification and genetic characterization of A. baumannii strains among patients in a tertiary level hospital in Mexico. Whole genome sequencing analysis was performed to establish their genetic relationship and drug resistance mutations profile. Ten genetically different, extensively drug resistant strains were identified circulating among seven wards. The genetic profiles showed resistance primarily against aminoglycosides and beta-lactam antibiotics. Importantly, no mutants conferring resistance to colistin were observed. The results highlight the importance of implementing robust classification schemes for advanced genetic characterization of A. baumannii clinical isolates and simultaneous detection of drug resistance markers for adequate patient’s management in clinical settings.

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<![CDATA[Antibiotic use for Australian Aboriginal children in three remote Northern Territory communities]]> https://www.researchpad.co/article/N999fa4e6-a15c-456a-862e-2e1ce88316a9

Objective

To describe antibiotic prescription rates for Australian Aboriginal children aged <2 years living in three remote Northern Territory communities.

Design

A retrospective cohort study using electronic health records.

Setting

Three primary health care centres located in the Katherine East region.

Participants

Consent was obtained from 149 mothers to extract data from 196 child records. There were 124 children born between January 2010 and July 2014 who resided in one of the three chosen communities and had electronic health records for their first two years of life.

Main outcome measures

Antibiotic prescription rates, factors associated with antibiotic prescription and factors associated with appropriate antibiotic prescription.

Results

There were 5,675 Primary Health Care (PHC) encounters for 124 children (median 41, IQR 25.5, 64). Of the 5,675 PHC encounters, 1,542 (27%) recorded at least one infection (total 1,777) and 1,330 (23%) had at least one antibiotic prescription recorded (total 1,468). Children had a median five (IQR 2, 9) prescriptions in both their first and second year of life, with a prescription rate of 5.99/person year (95% CI 5.35, 6.63). Acute otitis media was the most common infection (683 records, 38%) and Amoxycillin was the most commonly prescribed antibiotic (797 prescriptions, 54%). Of the 1,468 recorded prescriptions, 398 (27%) had no infection recorded and 116 (8%) with an infection recorded were not aligned with local treatment guidelines.

Conclusion

Prescription rates for Australian Aboriginal children in these communities are significantly higher than that reported nationally for non-Aboriginal Australians. Prescriptions predominantly aligned with treatment guidelines in this setting where there is a high burden of infectious disease.

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<![CDATA[Potential combinations of endocannabinoid/endocannabinoid-like compounds and antibiotics against methicillin-resistant Staphylococcus aureus]]> https://www.researchpad.co/article/Ne8a72c2e-13c7-43d3-9f49-0ed6410d9d0b

Infections caused by antibiotic-resistant strains of Staphylococcus aureus have reached epidemic proportions globally. Our previous study showed antimicrobial effects of anandamide (AEA) and arachidonoyl serine (AraS) against methicillin (MET)-resistant S. aureus (MRSA) strains, proposing the therapeutic potential of these endocannabinoid/endocannabinoid-like (EC/EC-like) agents for the treatment of MRSA. Here, we investigated the potential synergism of combinations of AEA and AraS with different types of antibiotics against MRSA grown under planktonic growth or biofilm formation. The most effective combinations under planktonic conditions were mixtures of AEA and ampicillin (AMP), and of AraS and gentamicin (GEN). The combination with the highest synergy in the biofilm formation against all tested bacterial strains was AEA and MET. Moreover, the combination of AraS and MET synergistically caused default of biofilm formation. Slime production of MRSA was also dramatically impaired by AEA or AraS combined with MET. Our data suggest the novel potential activity of combinations of EC/EC-like agents and antibiotics in the prevention of MRSA biofilm formation.

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<![CDATA[Quantitative dynamics of Salmonella and E. coli in feces of feedlot cattle treated with ceftiofur and chlortetracycline]]> https://www.researchpad.co/article/Nd45d35d0-8623-4716-b387-5e4fac70c4ad

Antibiotic use in beef cattle is a risk factor for the expansion of antimicrobial-resistant Salmonella populations. However, actual changes in the quantity of Salmonella in cattle feces following antibiotic use have not been investigated. Previously, we observed an overall reduction in Salmonella prevalence in cattle feces associated with both ceftiofur crystalline-free acid (CCFA) and chlortetracycline (CTC) use; however, during the same time frame the prevalence of multidrug-resistant Salmonella increased. The purpose of this analysis was to quantify the dynamics of Salmonella using colony counting (via a spiral-plating method) and hydrolysis probe-based qPCR (TaqMan® qPCR). Additionally, we quantified antibiotic-resistant Salmonella by plating to agar containing antibiotics at Clinical & Laboratory Standards Institute breakpoint concentrations. Cattle were randomly assigned to 4 treatment groups across 16 pens in 2 replicates consisting of 88 cattle each. Fecal samples from Days 0, 4, 8, 14, 20, and 26 were subjected to quantification assays. Duplicate qPCR assays targeting the Salmonella invA gene were performed on total community DNA for 1,040 samples. Diluted fecal samples were spiral plated on plain Brilliant Green Agar (BGA) and BGA with ceftriaxone (4 μg/ml) or tetracycline (16 μg/ml). For comparison purposes, indicator non-type-specific (NTS) E. coli were also quantified by direct spiral plating. Quantity of NTS E. coli and Salmonella significantly decreased immediately following CCFA treatment. CTC treatment further decreased the quantity of Salmonella but not NTS E. coli. Effects of antibiotics on the imputed log10 quantity of Salmonella were analyzed via a multi-level mixed linear regression model. The invA gene copies decreased with CCFA treatment by approximately 2 log10 gene copies/g feces and remained low following additional CTC treatment. The quantities of tetracycline or ceftriaxone-resistant Salmonella were approximately 4 log10 CFU/g feces; however, most of the samples were under the quantification limit. The results of this study demonstrate that antibiotic use decreases the overall quantity of Salmonella in cattle feces in the short term; however, the overall quantities of antimicrobial-resistant NTS E. coli and Salmonella tend to remain at a constant level throughout.

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<![CDATA[What can we learn by examining variations in the use of urine culture in the management of acute cystitis? A retrospective cohort study with linked administrative data in British Columbia, Canada, 2005-2011]]> https://www.researchpad.co/article/5c8c1954d5eed0c484b4d403

Introduction

Urinary tract infections (UTI) are common community-based bacterial infections. Empiric antibiotic recommendations are guided by local resistance rates. Previous research suggests that cultures are overused for uncomplicated cystitis, but practice patterns have not been described in detail. Variations in culturing have implications for the interpretation of antibiotic resistance rates.

Methods

We used a retrospective cohort study to analyze variations in urine culturing among physicians, controlling for patient and physician characteristics. We identified all outpatient physician visits among adults and children for cystitis in British Columbia between 2005 and 2011 using administrative data and linked these to laboratory data on urine cultures. Using hierarchical generalized linear mixed models we explored variations in urine culture submissions for cystitis (ICD code 595) and the associations with patient and physician characteristics, stratified by patient sex.

Results

Urine cultures were associated with 16% of visits for cystitis among females and 9% among males, and 59% of visits overall were associated with antibiotic treatment. Older patients, patients with a recent antibiotic prescription, and long term care residents were significantly less likely to have a culture associated with a cystitis visit, whether male or female. Female physicians and physicians with 16–35 years’ experience were more likely to culture, while international medical graduates were less likely–particularly for female visits. Notably, there was substantial unexplained variation among physicians after controlling for physician characteristics: we found a 24-fold variation in the odds of culturing a female UTI between physicians who were otherwise similar.

Conclusion

Individual physicians show substantial variation in their propensity to submit cultures for cystitis visits. Reducing such variation and encouraging appropriate levels of culturing would support effective antibiotic use.

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<![CDATA[Impact of pharmacist-led antibiotic stewardship interventions on compliance with surgical antibiotic prophylaxis in obstetric and gynecologic surgeries in Nigeria]]> https://www.researchpad.co/article/5c9902c2d5eed0c484b9852c

Background

Inappropriate and excessive use of surgical antibiotic prophylaxis are associated with the emergence of antibiotic resistance. Antibiotic prophylaxis malpractices are common in obstetrics and gynecology settings and antibiotic stewardship is used to correct such malpractice.

Objective

To evaluate the impact of antibiotic stewardship interventions on compliance with surgical antibiotic prophylaxis practice in obstetrics and gynecology surgeries.

Method

A prospective pre- and post-intervention study was conducted in two tertiary hospitals between May and December 2016. The duration of the each period was 3 months. Antibiotic stewardship interventions including development of a protocol, educational meeting and audit and feedback were implemented. Data were collected using the patient records and analyzed with SPSS version 23.

Results

A total of 226 and 238 surgical procedures were included in the pre- and post-intervention periods respectively. Age, length of stay and estimated blood loss were similar between the two groups. However, specialty and surgical procedures varied significantly. There was a significant increase in compliance with timing (from 14.2% to 43.3%) and duration (from 0% to 21.8%) of surgical antibiotic prophylaxis after the interventions. The interventions significantly reduced the prescription of third generation cephalosporin (-8.6%), redundant antibiotic (-19.1%), antibiotic utilization (-3.8 DDD/procedure) and cost of antibiotic prophylaxis (-$4.2/procedure). There was no significant difference in the rate of surgical site infection between the two periods. Post-intervention group (OR: 5.60; 95% CI: 3.31–9.47), elective surgery (OR: 4.62; 95% CI: 2.51–8.47) and hospital attended (OR: 9.89; 95% CI: 5.66–17.26) were significant predictors of compliance with timing while elective surgery (OR: 12.49; 95% CI: 2.85–54.71) and compliance with timing (OR: 58.55; 95% CI: 12.66–270.75) were significantly associated with compliance to duration of surgical antibiotic prophylaxis.

Conclusion

The interventions improve compliance with surgical antibiotic prophylaxis and reduce antibiotic utilization and cost. However, there is opportunity for further improvement, particularly in non-elective surgical procedures.

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<![CDATA[Cationic chitosan-propolis nanoparticles alter the zeta potential of S. epidermidis, inhibit biofilm formation by modulating gene expression and exhibit synergism with antibiotics]]> https://www.researchpad.co/article/5c818e84d5eed0c484cc2423

Staphylococcus epidermidis, is a common microflora of human body that can cause opportunistic infections associated with indwelling devices. It is resistant to multiple antibiotics necessitating the need for naturally occurring antibacterial agents. Malaysian propolis, a natural product obtained from beehives exhibits antimicrobial and antibiofilm properties. Chitosan-propolis nanoparticles (CPNP) were prepared using Malaysian propolis and tested for their effect against S. epidermidis. The cationic nanoparticles depicted a zeta potential of +40 and increased the net electric charge (zeta potential) of S. epidermidis from -17 to -11 mV in a concentration-dependent manner whereas, ethanol (Eth) and ethyl acetate (EA) extracts of propolis further decreased the zeta potential from -17 to -20 mV. Confocal laser scanning microscopy (CLSM) depicted that CPNP effectively disrupted biofilm formation by S. epidermidis and decreased viability to ~25% compared to Eth and EA with viability of ~60–70%. CPNP was more effective in reducing the viability of both planktonic as well as biofilm bacteria compared to Eth and EA. At 100 μg/mL concentration, CPNP decreased the survival of biofilm bacteria by ~70% compared to Eth or EA extracts which decreased viability by only 40%-50%. The morphology of bacterial biofilm examined by scanning electron microscopy depicted partial disruption of biofilm by Eth and EA extracts and significant disruption by CPNP reducing bacterial number in the biofilm by ~90%. Real time quantitative PCR analysis of gene expression in treated bacteria showed that genes involved in intercellular adhesion such as IcaABCD, embp and other related genes were significantly downregulated by CPNP. In addition to having a direct inhibitory effect on the survival of S. epidermidis, CPNP showed synergism with the antibiotics rifampicin, ciprofloxacin, vancomycin and doxycycline suggestive of effective treatment regimens. This would help decrease antibiotic treatment dose by at least 4-fold in combination therapies thereby opening up ways of tackling antibiotic resistance in bacteria.

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<![CDATA[Evaluation of Xpert MTB-RIF guided diagnosis and treatment of rifampicin-resistant tuberculosis in Indonesia: A retrospective cohort study]]> https://www.researchpad.co/article/5c818e93d5eed0c484cc25d9

Background

Rifampicin-resistant tuberculosis (RR-TB) is largely underdetected in Indonesia. Xpert MTB/RIF (Xpert) has recently been introduced, prioritizing patients at risk of RR-TB, followed by phenotypic drug-susceptibility (DST) if rifampicin resistance is detected.

Objective

This study investigated Xpert-based management of presumptive RR-TB cases under routine practice in West Java, Indonesia.

Methods

We examined all records of patients tested with Xpert in the referral hospital for West Java in 2015–2016. We measured loss across a limited cascade of care, time to Xpert diagnosis and the commencement of initial second-line treatment, and identified factors associated with diagnostic and treatment delay. Additionally, we analyzed the appropriateness of treatment according to DST results.

Results

Of 3415 patients with presumptive RR-TB, 3215 (94%) were tested by Xpert, of whom 339 (10.5%) were diagnosed as RR-TB. 288 (85%) of 339 RR-TB patients started initial second-line TB treatment, with 48 (14%) patients being lost between diagnosis and pre-treatment assessment. Second-line treatment was commenced at a median of 41 days (IQR 29–70) after RR-TB diagnosis. Delays in both diagnosis and treatment initiation were observed in 104 (52%) of 201 RR-TB patients with identifiable referral date. Rural residence was associated with delay to diagnosis (adjusted OR 2.7; 95%CI 1.5–5.2) and treatment initiation (adjusted OR 2.0; 1.2–3.4). Of 162 patients with available DST result, 107 (66%) had multidrug-resistant tuberculosis (MDR-TB) and 32 (20%) had either pre-extensively drug resistant (pre-XDR) or extensively drug resistant tuberculosis (XDR-TB). We estimated that with the current algorithm 41% of pre-XDR or XDR-TB patients are diagnosed, and 33% of them started on an appropriate treatment regimen.

Conclusions

Many patients with Xpert-diagnosed RR-TB either do not start MDR-TB treatment or encountered diagnostic and treatment delays under programmatic conditions in Indonesia, and most pre-XDR and XDR-TB cases remain undiagnosed. Further expansion and ongoing quality improvement of RR-TB services are urgently needed.

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<![CDATA[Surveillance of tuberculosis (TB) cases attributable to relapse or reinfection in London, 2002-2015]]> https://www.researchpad.co/article/5c70675ad5eed0c4847c6ed3

Recurrence of TB in an individual can occur due to relapse of the same strain or reinfection by a different strain. The contribution of reinfection and relapse to TB incidence, and the factors associated with each are unknown. We aimed to quantify and describe cases attributable to relapse or reinfection, and identify associated risk factors in order to reduce recurrence. We categorised recurrent TB cases from notifications in London (2002–2015) as relapse or reinfection using molecular (MIRU VNTR strain type) and epidemiological information (hierarchical approach using time since notification, site of disease and method of case finding). Factors associated with each outcome were determined using logistic regression in Stata Version 13.1 (2009–2015 only). Of 43,465 TB cases, 1.4% (618) were classified as relapse and 3.8% (1,637) as reinfection. The proportion with relapse decreased from 2002 (2.3%) to 2015 (1.3%), while the proportion of reinfection remained around 4%. Relapse was more common among recent migrants (<1 year, odds ratio (OR) = 1.99, p = 0.005), those with a social risk factor (OR = 1.51, p = 0.033) and those with central nervous system, spinal, miliary or disseminated TB (OR = 1.75, p = 0.001). Reinfection was more common among long term migrants (>11 years, OR = 1.67, p = <0.001), those with a social risk factor (OR = 1.96, p = <0.001) and within specific areas in London. Patients with social risk factors were at increased risk of both relapse and reinfection. Characterising those with relapsed disease highlights patients at risk and factors associated with reinfection suggest groups where transmission is occurring. This will inform TB control programs to target appropriate treatment and interventions in order to reduce the risk of recurrence.

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<![CDATA[A decade of antimicrobial resistance in Staphylococcus aureus: A single center experience]]> https://www.researchpad.co/article/5c6c75a1d5eed0c4843cff40

Background

The emergence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) resulted in the recommended use of clindamycin and trimethoprim-sulfamethoxazole (TMP-SMX) for suspected S. aureus infections. The objective of this study was to determine the resistance to methicillin, clindamycin, and TMP-SMX in S. aureus isolates during a 10-year period.

Methods

Retrospective review of the antimicrobial susceptibilities of all S. aureus isolates in the outpatient and inpatient settings at Nationwide Children’s Hospital from 1/1/2005 to 12/31/2014. Duplicate isolates from the same site and year and those obtained for MRSA surveillance or from patients with cystic fibrosis were excluded.

Results

Of the 57,788 S. aureus isolates from 2005–2014, 40,795 (71%) were included. In the outpatient setting, methicillin resistance decreased from 54% to 44% (p<0.001) while among inpatient isolates, no significant change was observed. From 2009–2014, resistance to clindamycin among outpatient isolates increased from 16% to 17% (p = 0.002) but no significant trend was observed among inpatient isolates (18% to 22%). Similarly, TMP-SMX resistance increased in outpatient S. aureus isolates from 2005–2014 (0.9% to 4%, p<0.001) but not among inpatient isolates. Among both inpatient and outpatient isolates, methicillin-susceptible S. aureus (MSSA) exhibited higher resistance to both clindamycin and TMP-SMX than MRSA. In addition, resistance to methicillin, clindamycin and TMP-SMX varied widely according to the site of specimen collection.

Conclusion

In a decade where >40,000 S. aureus isolates were identified at a large pediatric hospital, substantial changes in methicillin, clindamycin, and TMP-SMX resistance occurred. These findings highlight the importance of ongoing surveillance of the local antimicrobial resistance in S. aureus in order to guide empiric antimicrobial therapy.

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<![CDATA[Bridging antimicrobial resistance knowledge gaps: The East African perspective on a global problem]]> https://www.researchpad.co/article/5c6b2668d5eed0c484289a21

Background

There is worldwide concern of rapidly increasing antimicrobial resistance (AMR). However, there is paucity of resistance surveillance data and updated antibiograms in Africa in general. This study was undertaken in Kenyatta National Hospital (KNH) -the largest public tertiary referral centre in East & Central Africa—to help bridge existing AMR knowledge and practice gaps.

Methods

A retrospective review of VITEK 2 (bioMérieux) records capturing antimicrobial susceptibility data for the year 2015 was done and analysed using WHONET and SPSS.

Results

Analysis of 624 isolates revealed AMR rates higher than most recent local and international reports. 88% of isolates tested were multi-drug resistant (MDR) whereas 26% were extensively-drug resistant (XDR). E. coli and K. pneumoniae had poor susceptibility to penicillins (8–48%), cephalosporins (16–43%), monobactams (17–29%), fluoroquinolones (22–44%) and trimethoprim-sulfamethoxazole (7%). Pseudomonas aeruginosa and Acinetobacter baumanii were resistant to penicillins and cephalosporins, with reduced susceptibility to carbapenems (70% and 27% respectively). S aureus had poor susceptibility to penicillins (3%) and trimethoprim-sulfamethoxazole (29%) but showed excellent susceptibility to imipenem (90%), vancomycin (97%) and linezolid (99%).

Conclusions

The overwhelming resistance to commonly used antibiotics heralds a clarion call towards strengthening antimicrobial stewardship programmes and regular AMR regional surveillance.

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<![CDATA[Prediction of ultra-high-order antibiotic combinations based on pairwise interactions]]> https://www.researchpad.co/article/5c5b52b4d5eed0c4842bcea4

Drug combinations are a promising approach to achieve high efficacy at low doses and to overcome resistance. Drug combinations are especially useful when drugs cannot achieve effectiveness at tolerable doses, as occurs in cancer and tuberculosis (TB). However, discovery of effective drug combinations faces the challenge of combinatorial explosion, in which the number of possible combinations increases exponentially with the number of drugs and doses. A recent advance, called the dose model, uses a mathematical formula to overcome combinatorial explosion by reducing the problem to a feasible quadratic one: using data on drug pairs at a few doses, the dose model accurately predicts the effect of combinations of three and four drugs at all doses. The dose model has not yet been tested on higher-order combinations beyond four drugs. To address this, we measured the effect of combinations of up to ten antibiotics on E. coli growth, and of up to five tuberculosis (TB) drugs on the growth of M. tuberculosis. We find that the dose model accurately predicts the effect of these higher-order combinations, including cases of strong synergy and antagonism. This study supports the view that the interactions between drug pairs carries key information that largely determines higher-order interactions. Therefore, systematic study of pairwise drug interactions is a compelling strategy to prioritize drug regimens in high-dimensional spaces.

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<![CDATA[Efficacy assessment of commercially available natural products and antibiotics, commonly used for mitigation of pathogenic Vibrio outbreaks in Ecuadorian Penaeus (Litopenaeus) vannamei hatcheries]]> https://www.researchpad.co/article/5c5b52ebd5eed0c4842bd266

Bacterial diseases cause high mortality in Penaeus (Litopenaeus) vannamei postlarvae. Therefore, appropriate application of efficient therapeutic products is of vital importance for disease control. This study evaluated through in vitro analyses the antimicrobial effectiveness of commercial therapeutic products used for P. vannamei bacterial diseases and antibiotics against pathogenic Vibrio strains circulating in Ecuadorian hatcheries. Twenty strains were isolated from 31 larvae samples with high bacterial counts from 10 hatcheries collected during mortality events. The strains virulence was verified through challenge tests with Artemia franciscana nauplii and P. vannamei postlarvae. Through 16S rRNA sequence analysis, strains showed a great similarity to the Vibrio sequences reported as pathogens, with 95% belonging to the Harveyi clade. Through antibiograms and minimal inhibitory concentration (MIC) in vitro tests we found that furazolidone, ciprofloxacin, chloramphenicol, norfloxacin, nalidixic acid, florfenicol, fosfomycin and enrofloxacin inhibited the growth of all or most of the strains. Less efficient antibiotics were penicillin, oxytetracycline and tetracycline. A multiple antibiotic resistance (MAR) index of 0.23 showed some level of resistance to antibiotics, with two MAR prevalent patterns (Penicillin-Oxytetracycline and Penicillin-Oxytetracycline-Tetracycline). From a total of 16 natural products (five probiotics, nine organic acids and two essential oils), only three (one probiotic, one organic acid and one essential oil) were effective to control most of the strains. Shrimp producers can apply relatively simple in vitro analyses, such as those employed in this study, to help take adequate management decisions to reduce the impact of bacterial diseases and increase profit.

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<![CDATA[Spread of ceftriaxone non-susceptible pneumococci in South Korea: Long-term care facilities as a potential reservoir]]> https://www.researchpad.co/article/5c5b52afd5eed0c4842bce46

Despite the availability of a pneumococcal National Immunization Program, which provides free PPSV23 vaccination for older adults aged ≥65 years in South Korea, pneumococcal pneumonia remains one of the most common respiratory infections, with increasing antimicrobial resistance. From January to December in 2015, all pneumococcal isolates were collected from a 1,050-bed teaching hospital in South Korea. All isolates were analyzed for serotype, genotype, and antimicrobial susceptibility. Demographic, clinical and microbiological data were compared between ceftriaxone susceptible and non-susceptible cases. Among 92 microbiologically identified pneumococcal isolates, ceftriaxone non-susceptible pneumococci (CNSP) accounted for 32 cases (34.8%). Some of these cases also showed levofloxacin resistance (25%, 8/32 isolates) and all CNSP cases were multidrug resistant. Compared to patients with ceftriaxone susceptible pneumococci (CSP), long-term care facility residents (odds ratio [OR] 7.0, 95% confidence interval [CI] 0.8–62.1) and patients with chronic lung (OR 4.1, 95% CI 1.1–15.0) and renal diseases (OR 9.1, 95% CI 1.2–70.5) were more common among those with CNSP on multivariate analysis. PPSV23-unique serotypes not included in PCV13 were more common in CNSP than in CSP (34.4% versus 13.3%, p = 0.02). Regarding genotypes, ST320 (10 cases), ST166 (7 cases) and ST8279 (3 cases) were dominant in CNSP, and ST8279 was only detected in previous long-term care facility residents. Clonal expansion and spread of CNSP strains should be monitored among patients with chronic lung/renal diseases and residents of long-term care facilities.

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<![CDATA[Impact of a smartphone app on prescriber adherence to antibiotic guidelines in adult patients with community acquired pneumonia or urinary tract infections]]> https://www.researchpad.co/article/5c59fec8d5eed0c484135447

Background

Mobile phone apps have been shown to enhance guideline adherence by prescribers, but have not been widely evaluated for their impact on guideline adherence by prescribers caring for inpatients with infections.

Objectives

To determine whether providing the Auckland City Hospital (ACH) antibiotic guidelines in a mobile phone app increased guideline adherence by prescribers caring for inpatients with community acquired pneumonia (CAP) or urinary tract infections (UTIs).

Methods

We audited antibiotic prescribing during the first 24 hours after hospital admission in adults admitted during a baseline and an intervention period to determine whether provision of the app increased the level of guideline adherence. To control for changes in prescriber adherence arising from other factors, we performed similar audits of adherence to antibiotic guidelines in two adjacent hospitals.

Results

The app was downloaded by 145 healthcare workers and accessed a total of 3985 times during the three month intervention period. There was an increase in adherence to the ACH antibiotic guidelines by prescribers caring for patients with CAP from 19% (37/199) to 27% (64/237) in the intervention period (p = 0.04); but no change in guideline adherence at an adjacent hospital. There was no change in adherence to the antibiotic guidelines by prescribers caring for patients with UTI at ACH or at the two adjacent hospitals.

Conclusions

Provision of antibiotic guidelines in a mobile phone app can significantly increase guideline adherence by prescribers. However, providing an app which allows easy access to antibiotic guidelines is not sufficient to achieve high levels of prescriber adherence.

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<![CDATA[Cyclodextrins as multifunctional excipients: Influence of inclusion into β-cyclodextrin on physicochemical and biological properties of tebipenem pivoxil]]> https://www.researchpad.co/article/5c57e6e3d5eed0c484ef418c

A novel approach for drug design based on the oral carbapenem analog tebipenem pivoxil (TP) has been proposed. The formation of the tebipenem pivoxil-β-cyclodextrin (TP-β-CD) complex resulted in changes concerning physicochemical properties of TP, which is significant for planning the development of an innovative pharmaceutical formulation as well as in the modifications of biological activity profile of the studied delivery system. The inclusion of TP into β-cyclodextrin (β-CD) was confirmed by spectral (infrared and Raman spectroscopies) and thermal method (differential scanning calorimetry). Precise indications of TP domains responsible for interaction with β-CD were possible through a theoretical approach. The most important physicochemical modifications obtained as an effect of TP inclusion were changes in solubility and its rate depending on acceptor fluids, and an increase in chemical stability in the solid state. Biologically essential effects of TP and β-CD interactions were decreased TP permeability through Caco–2 cell monolayers with the use of efflux effect inhibition and increased antibacterial activity. The proposed approach is an opportunity for development of the treatment in resistant bacterial infections, in which along with physicochemical modifications induced by a drug carrier impact, a carrier synergy with a pharmacological potential of an active pharmaceutical substance could be used.

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<![CDATA[The impact of improved detection and treatment of isoniazid resistant tuberculosis on prevalence of multi-drug resistant tuberculosis: A modelling study]]> https://www.researchpad.co/article/5c5369f3d5eed0c484a46b1f

Introduction

Isoniazid-resistant, rifampin susceptible tuberculosis (INHR-TB) is the most common form of drug resistant TB globally. Treatment of INHR-TB with standard first-line therapy is associated with high rates of multidrug resistant TB (MDR-TB). We modelled the potential impact of INHR-TB detection and appropriate treatment on MDR-TB prevalence.

Methods

A decision analysis model was developed to compare three different strategies for the detection of TB (AFB smear, Xpert MTB/RIF, and Line-Probe Assays (LPA)), combined with appropriate treatment. The population evaluated were patients with a globally representative prevalence of newly diagnosed, drug-susceptible (88.6%), isoniazid-resistant (7.3%), and multidrug resistant (4.1%) pulmonary TB. Our primary outcome was the proportion of patients with MDR-TB after initial attempt at diagnosis and treatment within a 2-year period. Secondary outcomes were the proportion of i) individuals with detected TB who acquired MDR-TB ii) individuals who died after initial attempt at diagnosis and treatment.

Results

After initial attempt at diagnosis and treatment, LPA combined with appropriate INHR-TB therapy resulted in a lower proportion of prevalent MDR-TB (1.61%; 95% Uncertainty Range (UR: 2.5th and 97.5th percentiles generated from 10 000 Monte Carlo simulation trials) 1.61–1.65), when compared to Xpert (1.84%; 95% UR 1.82–1.85) and AFB smear (3.21%; 95% UR 3.19–3.26). LPA also resulted in fewer cases of acquired MDR-TB in those with detected TB (0.35%; 95% UR 0.34–0.35), when compared to Xpert (0.67%; 95% UR 0.65–0.67) and AFB smear (0.68%; 95% UR 0.67–0.69). The majority of acquired MDR-TB arose from the treatment of INHR-TB in all strategies. Xpert-based strategies resulted in a lower proportion of death (2.89%; 95% UR 2.87–2.90) compared to LPA (2.93%; 95% UR 2.91–2.94) and AFB smear (3.21%; 95% UR 3.19–3.23).

Conclusion

Accurate diagnosis and tailored treatment of INHR-TB with LPA led to an almost 50% relative decrease in acquired MDR-TB when compared with an Xpert MTB/RIF strategy. Continued reliance on diagnostic and treatment protocols that ignore INHR-TB will likely result in further generation of MDR-TB.

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