scholarly journals Tebipenem as an oral alternative for the treatment of typhoid caused by extensively drug resistant (XDR) Salmonella Typhi

2021 ◽  
Author(s):  
Elli Mylona ◽  
Phat Voong Vinh ◽  
Sonia Qureshi ◽  
Abhilasha Karkey ◽  
Sabina Dongol ◽  
...  
Keyword(s):  
Enteric Fever ◽  
Salmonella Typhi ◽  
Drug Resistant ◽  
Extensively Drug Resistant ◽  
Extensive Drug Resistance ◽  
Spectrum Activity ◽  
Fever Treatment ◽  
Emergence Of Resistance ◽  
Broad Spectrum Activity

Abstract The emergence of multi-drug (MDR) and extensive-drug resistance (XDR) in Salmonella Typhi and Paratyphi A hinder efficacious out-patient enteric fever treatment. We show that non-XDR and XDR S. Typhi and S. Paratyphi A are susceptible to the carbapenem tebipenem in vitro. Tebipenem demonstrated partial synergy with antimicrobials including azithromycin, signifying combination therapy may limit the emergence of resistance. Given recent evidence on tebipenem inhibitory activity against MDR Shigella, its broad-spectrum activity against MDR/XDR organisms renders it a good clinical trial candidate.

scholarly journals Antibacterial Activity of Manuka Honey Against Azithromycin Resistant Extensively Drug Resistant Salmonella Typhi Clinical Isolates: In-Vitro Study

2022 ◽  
Author(s):  
Kokab Jabeen ◽  
Sidrah Saleem ◽  
Faiqa Arshad ◽  
Zill-e-Huma ◽  
Shah Jahan ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Alternative Treatment ◽  
Therapeutic Potential ◽  
Salmonella Typhi ◽  
Drug Resistant ◽  
Manuka Honey ◽  
Extensively Drug Resistant ◽  
Alternative Treatment Option ◽  
Wide Range

Abstract Typhoid fever is a significant health problem in developing countries like Pakistan. Salmonella Typhi the causative agent of typhoid has developed resistant to almost all recommended antibiotics. Emergence of resistance to third generation cephalosporins has further complicated the situation and such strains are called as extensively drug resistant (XDR) Salmonella Typhi. Currently only available options are azithromycin and cabapenems. Recently few reports of azithromycin resistance have emerged from countries like Pakistan, India, Bangladesh and Nepal. As azithromycin is the only oral option available to treat XDR Typhoid, development of resistance may change treatment strategy altogether from out patient management to hospitalization of every patient. This may increase the burden on already weak health care system of countries like Pakistan. So there is dire need to look for the alternative treatment options. Manuka honey is well known for its therapeutic potential against wide range of bacteria including Salmonella Typhimurium. In this study 3 azithromycin resistant isolates were isolated and identified using disc diffusion, E-test and broth micro dilution methods and antibacterial activity, MIC and MBC of manuka honey was performed by agar well diffusion assay and broth micro dilution assay respectively. Manuka honey manifested significant antibacterial activity against all test isolates with zone of inhibition ranging from 7.3mm to 7.5mm, MIC and MBC values were between 10 to 15% v/v Here, we conclude that Manuka honey possess potent antibacterial activity and might be used as an alternative treatment option against azithromycin resistant XDR Typhid. However, further clinical trials are mandatory to validate our initial findings.

scholarly journals Characterization of Plasmids in Extensively Drug-Resistant Acinetobacter Strains Isolated in India and Pakistan

2014 ◽  
Vol 59 (2) ◽  
pp. 923-929 ◽  
Author(s):  
Lim S. Jones ◽  
Maria J. Carvalho ◽  
Mark A. Toleman ◽  
P. Lewis White ◽  
Thomas R. Connor ◽  
...  
Keyword(s):  
Selection Pressure ◽  
Gram Negative Bacteria ◽  
Drug Resistant ◽  
Content Type ◽  
Extensively Drug Resistant ◽  
Extensive Drug Resistance ◽  
Acinetobacter Haemolyticus ◽  
Insight Into

ABSTRACTTheblaNDM-1gene is associated with extensive drug resistance in Gram-negative bacteria. This probably spread toEnterobacteriaceaefromAcinetobacterspp., and we characterized plasmids associated withblaNDM-1inAcinetobacterspp. to gain insight into their role in this dissemination. Four clinical NDM-1-producingAcinetobacterspecies strains from India and Pakistan were investigated. A plasmid harboringblaNDM-1, pNDM-40-1, was characterized by whole-genome sequencing ofAcinetobacter bereziniaeCHI-40-1 and comparison with related plasmids. The presence of similar plasmids in strains from Pakistan was sought by PCR and sequencing of amplicons. Conjugation frequency was tested and stability of pNDM-40-1 investigated by real-time PCR of isolates passaged with and without antimicrobial selection pressure.A. bereziniaeandAcinetobacter haemolyticusstrains contained plasmids similar to the pNDM-BJ01-like plasmids identified inAcinetobacterspp. in China. The backbone of pNDM-40-1 was almost identical to that of pNDM-BJ01-like plasmids, but the transposon harboringblaNDM-1, Tn125, contained two short deletions.Escherichia coliandAcinetobacterpittiitransconjugants were readily obtained. Transconjugants retained pNDM-40-1 after a 14-day passage experiment, although stability was greater with meropenem selection. Fragments of pNDM-BJ01-like plasmid backbones are found nearblaNDM-1in some genetic contexts fromEnterobacteriaceae, suggesting that cross-genus transfer has occurred. pNDM-BJ01-like plasmids have been described in isolates originating from a wide geographical region in southern Asia.In vitrodata on plasmid transfer and stability suggest that these plasmids could have contributed to the spread ofblaNDM-1intoEnterobacteriaceae.

scholarly journals In VitroActivity of Polymyxin B in Combination with Various Antibiotics against Extensively Drug-Resistant Enterobacter cloacae with Decreased Susceptibility to Polymyxin B

2016 ◽  
Vol 60 (9) ◽  
pp. 5238-5246 ◽  
Author(s):  
Yiying Cai ◽  
Tze-Peng Lim ◽  
Jocelyn Teo ◽  
Suranthran Sasikala ◽  
Winnie Lee ◽  
...  
Keyword(s):  
Enterobacter Cloacae ◽  
Polymyxin B ◽  
Infection Model ◽  
Drug Resistant ◽  
Content Type ◽  
Extensively Drug Resistant ◽  
Dosing Regimens ◽  
Time Kill ◽  
Emergence Of Resistance

ABSTRACTAgainst extensively drug-resistant (XDR)Enterobacter cloacae, combination antibiotic therapy may be the only option. We investigated the activity of various antibiotics in combination with polymyxin B using time-kill studies (TKS). TKS were conducted with four nonclonal XDRE. cloacaeisolates with 5 log10CFU/ml bacteria against maximum, clinically achievable concentrations of polymyxin B alone and in two-drug combinations with 10 different antibiotics. A hollow-fiber infection model (HFIM) simulating clinically relevant polymyxin B and tigecycline dosing regimens was conducted for two isolates over 240 h. Emergence of resistance was quantified using antibiotic-containing (3× MIC) media. Biofitness and stability of resistant phenotypes were determined. All XDRE. cloacaeisolates were resistant to all antibiotics except for polymyxin B (polymyxin B MIC, 1 to 4 mg/liter). All isolates harbored metallo-β-lactamases (two with NDM-1, two with IMP-1). In single TKS, all antibiotics alone demonstrated regrowth at 24 h, except amikacin against two strains and polymyxin B and meropenem against one strain each. In combination TKS, only polymyxin B plus tigecycline was bactericidal against all four XDRE. cloacaeisolates at 24 h. In HFIM, tigecycline and polymyxin B alone did not exhibit any killing activity. Bactericidal kill was observed at 24 h for both isolates for polymyxin B plus tigecycline; killing was sustained for one isolate but regrowth was observed for the second. Phenotypically stable resistant mutants with reducedin vitrogrowth rates were observed. Polymyxin B plus tigecycline is a promising combination against XDRE. cloacae. However, prolonged and indiscriminate use can result in resistance emergence.

scholarly journals In VitroActivities of Novel Antimicrobial Combinations against Extensively Drug-Resistant Acinetobacter baumannii

2015 ◽  
Vol 59 (12) ◽  
pp. 7316-7319 ◽  
Author(s):  
J. Córdoba ◽  
N. M. Coronado-Álvarez ◽  
D. Parra ◽  
J. Parra-Ruiz
Keyword(s):  
Acinetobacter Baumannii ◽  
Limit Of Detection ◽  
Single Agent ◽  
Drug Resistant ◽  
Content Type ◽  
Development Of Resistance ◽  
Extensively Drug Resistant ◽  
Combination Regimens ◽  
Emergence Of Resistance

ABSTRACTExtensively drug-resistant (XDR)Acinetobacterspp. have emerged as a cause of nosocomial infections, especially under conditions of intensive care. Unfortunately, resistance to colistin is increasing and there is a need for new therapeutic options. We aimed to study the effect of some novel combinations against XDRAcinetobacter baumanniiin anin vitropharmacokinetics-pharmacodynamics (PK/PD) model. Three nonrelated clinical strains of XDRA. baumanniiwere investigated. Antibiotic-simulated regimens were colistin at 3 MU every 8 h (q8h) (first dose, 6 MU), daptomycin at 10 mg/kg of body weight q24h, imipenem at 1 g q8h, and ertapenem at 1 g q24h. Combination regimens included colistin plus daptomycin, colistin plus imipenem, and imipenem plus ertapenem. Samples were obtained at 0, 1, 2, 4, 8, and 24 h. Among the single-agent regimens, only the colistin regimen resulted in significant reductions in log10CFU per milliliter compared to the control for all the strains tested. Although colistin achieved bactericidal activity at 4 h, it was not able to reach the limit of detection (1 log10CFU/ml). One strain had significant regrowth at 24 h without the emergence of resistance. Daptomycin-colistin combinations led to a significant reduction in levels of log10CFU per milliliter that were better than those achieved with colistin as a single-agent regimen, reaching the limit of detection at 24 h against all the strains. The combination of imipenem plus ertapenem outperformed the colistin regimen, although the results did not reach the limit of detection, with significant regrowth at 24 h. Similarly, colistin-plus-imipenem combinations reduced the levels of log10CFU per milliliter at 8 h, with significant regrowth at 24 h but with development of resistance to colistin. We have shown some potentially useful alternatives for the treatment of extensively drug-resistantA. baumannii. Among them, the daptomycin-colistin combination was the most effective and should be investigated in future studies.

scholarly journals A review of clinical profile, complications and antibiotic susceptibility pattern of extensively drug-resistant (XDR) Salmonella Typhi isolates in children in Karachi.

2020 ◽  
Author(s):  
Saba Shahid ◽  
Marvi Mahesar ◽  
Nida Ghouri ◽  
Saba Noreen
Keyword(s):  
Enteric Fever ◽  
Clinical Course ◽  
Pediatric Population ◽  
Clinical Manifestations ◽  
Systemic Infection ◽  
Retrospective Chart Review ◽  
Signs And Symptoms ◽  
Salmonella Typhi ◽  
Drug Resistant ◽  
Extensively Drug Resistant

Abstract Background: Enteric fever is a systemic infection, which can be caused by Salmonella enterica; Typhi and Paratyphi A. Over time, Salmonella Typhi has developed resistance to antibiotics resulting in the emergence of extensively drug-resistant (XDR) enteric fever. WHO estimated 5274 cases of XDR Enteric fever in Karachi from November 2016 to December 2019. This study aims to determine clinical course, complications and outcomes of XDR enteric fever among the pediatric population coming to Indus HospitalMethods: A retrospective chart review of pediatric patients (aged one month to 15 years) seen in Indus Hospital between July 2017 to December 2018 was conducted. A pre-designed data abstraction form was used to record detailed information about seasonality and distribution of cases, demographic details, signs and symptoms, clinical course, treatment, complications and outcomes of the cases treated for XDR Enteric feverResults: Six hundred and eighty children were included in the study. The median (IQR) age of the patients was 5 (2-8) years. More than half (n=391, 57.5%) of the patients were males. Most common clinical manifestations included fever, vomiting and diarrhea, noted in 680 (100%), 242 (35%) and 174 (25%) patients. Outcomes of 270 (39.7%) patients were recorded. Others were lost to follow up [351 (51.6%)], referred out [52 (7.6%)] or left against medical advice [7 (1%)]. 266 (39.1%) patients were cured, and four children (0.6%) expired. Seventy-eight patients (82%) and 15 patients (16.3%) got cured on Azithromycin and Meropenem alone while 157 on a combination of drugs.Conclusion: Our review indicated that children under five years of age were affected more with XDR Enteric fever. Meropenem and Azithromycin, either alone or in combination were the most effective antibiotics for treating XDR Enteric fever in children coming to Indus hospital

scholarly journals A review of clinical profile, complications and antibiotic susceptibility pattern of extensively drug resistant (XDR) Salmonella Typhi isolates in children in Karachi.

2020 ◽  
Author(s):  
Saba Shahid ◽  
Marvi Mahesar ◽  
Nida Ghouri ◽  
Saba Noreen
Keyword(s):  
Enteric Fever ◽  
Clinical Course ◽  
Pediatric Population ◽  
Clinical Manifestations ◽  
Systemic Infection ◽  
Retrospective Chart Review ◽  
Signs And Symptoms ◽  
Salmonella Typhi ◽  
Drug Resistant ◽  
Extensively Drug Resistant

Abstract Background: Enteric fever is a systemic infection, which can be caused by Salmonella enterica; Typhi and Paratyphi A. Over a period of time Salmonella Typhi has developed resistance to many antibiotics which has resulted in emergence of extensively drug resistant (XDR) enteric fever. WHO estimated 5274 cases of XDR Enteric fever in Karachi from November 2016 to December 2019.This study aims to determine clinical course, complications and outcomes of XDR enteric fever among the pediatric population coming to Indus HospitalMethods: A retrospective chart review of pediatric patients (aged 1 month–15 years) seen in Indus Hospital between July 2017 to December 2018 was conducted. A pre-designed data abstraction form was used to record detailed information about seasonality and distribution of cases, demographic details, signs and symptoms, clinical course, treatment, complications and final outcomes of the cases treated for XDR Enteric feverResults: Six hundred and eighty children were included in the study. The median (IQR) age of the patients was 5 (2-8) years. More than half (n=391, 57.5%) of the patients were males. Most common clinical manifestations included fever vomiting and diarrhea which were noted in 680 (100%), 242 (35%) and 174 patients (25%) Final outcomes of 270 (39.7%) patients have been recorded; 351 (51.6%) were lost to follow up, 52 (7.6%) were referred out and 7 (1%) left without medical advice. 266 (39.1%) patients were cured and 4 children (0.6%) expired. Seventy eight patients (82%) and 15 patients (16.3%) got cured on Azithromycin and Meropenum alone while 157 patients got cured on combination of drugs.Conclusion: Our review indicated that children under 5 years of age were affected more with XDR Enteric fever. Meropenum and Azithromycin, either alone or in combination were the most effective antibiotics for treating XDR Enteric fever in children coming to Indus hospital

scholarly journals Comparison of In Vitro Activity and MIC Distributions between the Novel Oxazolidinone Delpazolid and Linezolid against Multidrug-Resistant and Extensively Drug-Resistant Mycobacterium tuberculosis in China

2018 ◽  
Vol 62 (8) ◽  
Author(s):  
Zhaojing Zong ◽  
Wei Jing ◽  
Jin Shi ◽  
Shu'an Wen ◽  
Tingting Zhang ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Novel Mutation ◽  
Multidrug Resistant ◽  
23S Rrna ◽  
Drug Resistant ◽  
Content Type ◽  
Extensively Drug Resistant ◽  
Significant Difference ◽  
Mdr Tb

ABSTRACT Oxazolidinones are efficacious in treating mycobacterial infections, including tuberculosis (TB) caused by drug-resistant Mycobacterium tuberculosis. In this study, we compared the in vitro activities and MIC distributions of delpazolid, a novel oxazolidinone, and linezolid against multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) in China. Additionally, genetic mutations in 23S rRNA, rplC, and rplD genes were analyzed to reveal potential mechanisms underlying the observed oxazolidinone resistance. A total of 240 M. tuberculosis isolates were included in this study, including 120 MDR-TB isolates and 120 XDR-TB isolates. Overall, linezolid and delpazolid MIC90 values for M. tuberculosis isolates were 0.25 mg/liter and 0.5 mg/liter, respectively. Based on visual inspection, we tentatively set epidemiological cutoff (ECOFF) values for MIC determinations for linezolid and delpazolid at 1.0 mg/liter and 2.0 mg/liter, respectively. Although no significant difference in resistance rates was observed between linezolid and delpazolid among XDR-TB isolates (P > 0.05), statistical analysis revealed a significantly greater proportion of linezolid-resistant isolates than delpazolid-resistant isolates within the MDR-TB group (P = 0.036). Seven (53.85%) of 13 linezolid-resistant isolates were found to harbor mutations within the three target genes. Additionally, 1 isolate exhibited an amino acid substitution (Arg126His) within the protein encoded by rplD that contributed to high-level resistance to linezolid (MIC of >16 mg/liter), compared to a delpazolid MIC of 0.25. In conclusion, in vitro susceptibility testing revealed that delpazolid antibacterial activity was comparable to that of linezolid. A novel mutation within rplD that endowed M. tuberculosis with linezolid, but not delpazolid, resistance was identified.

scholarly journals Discovery and Characterization of a Novel CD4-Binding Adnectin with Potent Anti-HIV Activity

2017 ◽  
Vol 61 (8) ◽  
Author(s):  
David Wensel ◽  
Yongnian Sun ◽  
Zhufang Li ◽  
Sharon Zhang ◽  
Caryn Picarillo ◽  
...  
Keyword(s):  
Conformational Changes ◽  
Viral Entry ◽  
High Affinity ◽  
Glycosylation Sites ◽  
Spectrum Activity ◽  
Anti Hiv ◽  
Hiv 1 ◽  
Broad Spectrum Activity

ABSTRACT A novel fibronectin-based protein (Adnectin) HIV-1 inhibitor was generated using in vitro selection. This inhibitor binds to human CD4 with a high affinity (3.9 nM) and inhibits viral entry at a step after CD4 engagement and preceding membrane fusion. The progenitor sequence of this novel inhibitor was selected from a library of trillions of Adnectin variants using mRNA display and then further optimized for improved antiviral and physical properties. The final optimized inhibitor exhibited full potency against a panel of 124 envelope (gp160) proteins spanning 11 subtypes, indicating broad-spectrum activity. Resistance profiling studies showed that this inhibitor required 30 passages (151 days) in culture to acquire sufficient resistance to result in viral titer breakthrough. Resistance mapped to the loss of multiple potential N-linked glycosylation sites in gp120, suggesting that inhibition is due to steric hindrance of CD4-binding-induced conformational changes.

scholarly journals In Vitro Activity of the Novel Pleuromutilin Lefamulin (BC-3781) and Effect of Efflux Pump Inactivation on Multidrug-Resistant and Extensively Drug-Resistant Neisseria gonorrhoeae

2017 ◽  
Vol 61 (11) ◽  
Author(s):  
Susanne Jacobsson ◽  
Susanne Paukner ◽  
Daniel Golparian ◽  
Jörgen S. Jensen ◽  
Magnus Unemo
Keyword(s):  
Efflux Pump ◽  
Multidrug Resistant ◽  
Cross Resistance ◽  
Drug Resistant ◽  
The Novel ◽  
Extensively Drug Resistant ◽  
Optimal Dosing ◽  
And Performance ◽  
Reference Strains

ABSTRACT We evaluated the activity of the novel semisynthetic pleuromutilin lefamulin, inhibiting protein synthesis and growth, and the effect of efflux pump inactivation on clinical gonococcal isolates and reference strains (n = 251), including numerous multidrug-resistant and extensively drug-resistant isolates. Lefamulin showed potent activity against all gonococcal isolates, and no significant cross-resistance to other antimicrobials was identified. Further studies of lefamulin are warranted, including in vitro selection and mechanisms of resistance, pharmacokinetics/pharmacodynamics, optimal dosing, and performance in randomized controlled trials.

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