Can We Prevent Antimicrobial Resistance by Using Antimicrobials Better?

Soothill, Germander; Hu, Yan; Coates, Anthony R. M.

doi:10.3390/pathogens2020422

Cited by 31 publications

(20 citation statements)

References 82 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The combination of anti-infective compounds to expand the antimicrobial spectrum, improve the therapeutic outcome, and diminish the emergence of resistance is a well-established strategy in antimicrobial chemotherapy [11][12][13]. Several antimicrobial combinations have recently been explored against difficult-to-treat MDR and XDR Gram-negative pathogens, and synergism was often reported for colistin (a clinically used AMP) or other AMPs in combination with rifampin or carbapenems and other β-lactams [14][15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Synergistic activity profile of an antimicrobial peptide against multidrug‐resistant and extensively drug‐resistant strains of Gram‐negative bacterial pathogens

Pollini

Brunetti

Sennati

et al. 2017

Journal of Peptide Science

View full text Add to dashboard Cite

Infection sustained by multidrug-resistant and extensively drug-resistant bacterial pathogens is often untreatable with the standard of care antibiotics, and the combination of anti-infective compounds often represents the only therapeutic strategy to face this major clinical treat. SET-M33 is a novel antimicrobial peptide (AMP) that has demonstrated in vitro and in vivo antimicrobial activity against Gram-negative bacteria and has shown interesting features in preclinical evaluations. Particularly, it showed efficacy against a number of multidrug-resistant and extensively drug-resistant clinical strains of Gram-negative pathogens, in in vitro and in vivo assessments. Here, we explored the potential synergistic activity of SET-M33 in combination with different standard of care antibiotics by the checkerboard method against a panel of six strains of Gram-negative pathogens including multidrug-resistant and extensively drug-resistant Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii. SET-M33 showed synergistic activity with antibiotics of different families against these clinically relevant strains. A synergistic effect was observed for SET-M33 in combination with rifampin, meropenem, aztreonam, and tobramycin mostly on K. pneumoniae and A. baumannii strains, while the SET-M33 plus ciprofloxacin combination was additive with all tested strains. Synergy was not apparently linked to the bacterial species or phenotype but was rather strain-specific, highlighting the need for individual strain testing for synergistic antimicrobial combinations. These findings extend current knowledge on synergistic activity of AMPs in combination with conventional agents and support the potential role of SET-M33 as a novel therapeutic agent against antibiotic-resistant Gram-negative pathogens. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.

show abstract

Section: Introductionmentioning

confidence: 99%

Synergistic activity profile of an antimicrobial peptide against multidrug‐resistant and extensively drug‐resistant strains of Gram‐negative bacterial pathogens

Pollini

Brunetti

Sennati

et al. 2017

Journal of Peptide Science

View full text Add to dashboard Cite

show abstract

“…Poor antibiotic stewardship is a key driver of antibiotic resistance [7]. A substantial proportion of all antibiotics are prescribed in the community [8], and Upper Respiratory Tract Infection (URTI) is one of the commonest conditions in the primary care setting for which antibiotic prescriptions have been reported to be high worldwide [9–11].…”

Section: Introductionmentioning

confidence: 99%

Knowledge, attitudes and practices towards antibiotic use in upper respiratory tract infections among patients seeking primary health care in Singapore

et al. 2016

View full text Add to dashboard Cite

BackgroundPatients’ expectations can influence antibiotic prescription by primary healthcare physicians. We assessed knowledge, attitude and practices towards antibiotic use for upper respiratory tract infections (URTIs), and whether knowledge is associated with increased expectations for antibiotics among patients visiting primary healthcare services in Singapore.MethodsData was collected through a cross-sectional interviewer-assisted survey of patients aged ≥21 years waiting to see primary healthcare practitioners for one or more symptoms suggestive of URTI (cough, sore throat, runny nose or blocked nose) for 7 days or less, covering the demographics, presenting symptoms, knowledge, attitudes, beliefs and practices of URTI and associated antibiotic use. Univariate and multivariate logistic regression was used to assess independent factors associated with patients’ expectations for antibiotics.ResultsNine hundred fourteen out of 987 eligible patients consulting 35 doctors were recruited from 24 private sector primary care clinics in Singapore. A third (307/907) expected antibiotics, of which a substantial proportion would ask the doctor for antibiotics (121/304, 40 %) and/or see another doctor (31/304, 10 %) if antibiotics were not prescribed. The majority agreed “antibiotics are effective against viruses” (715/914, 78 %) and that “antibiotics cure URTI faster” (594/912, 65 %). Inappropriate antibiotic practices include “keeping antibiotics stock at home” (125/913, 12 %), “taking leftover antibiotics” (114/913, 14 %) and giving antibiotics to family members (62/913, 7 %). On multivariate regression, the following factors were independently associated with wanting antibiotics (odds ratio; 95 % confidence interval): Malay ethnicity (1.67; 1.00–2.79), living in private housing (1.69; 1.13–2.51), presence of sore throat (1.50; 1.07–2.10) or fever (1.46; 1.01–2.12), perception that illness is serious (1.70; 1.27–2.27), belief that antibiotics cure URTI faster (5.35; 3.76–7.62) and not knowing URTI resolves on its own (2.18; 1.08–2.06), while post-secondary education (0.67; 0.48–0.94) was inversely associated. Those with lower educational levels were significantly more likely to have multiple misconceptions about antibiotics.ConclusionMajority of patients seeking primary health care in Singapore are misinformed about the role of antibiotics in URTI. Agreeing with the statement that antibiotics cure URTI faster was most strongly associated with wanting antibiotics. Those with higher educational levels were less likely to want antibiotics, while those with lower educational levels more likely to have incorrect knowledge.Electronic supplementary materialThe online version of this article (doi:10.1186/s12875-016-0547-3) contains supplementary material, which is available to authorized users.

show abstract

“…Research is warranted to identify new combinations of drugs acting on different targets concurrently. It has been hypothesized that combination antimicrobial therapy may prevent or delay development of resistance [ 3 ]. Promising results have been shown by combining antimicrobials with small non-antimicrobial helper molecules interfering with resistance [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Antimicrobial synergy between carprofen and doxycycline against methicillin-resistant Staphylococcus pseudintermedius ST71

et al. 2016

View full text Add to dashboard Cite

BackgroundNew therapeutic strategies are needed to face the rapid spread of multidrug-resistant staphylococci in veterinary medicine. The objective of this study was to identify synergies between antimicrobial and non-antimicrobial drugs commonly used in companion animals as a possible strategy to restore antimicrobial susceptibility in methicillin-resistant Staphylococcus pseudintermedius (MRSP).ResultsA total of 216 antimicrobial/non-antimicrobial drug combinations were screened by disk diffusion using a clinical MRSP sequence type (ST) 71 strain resistant to all six antimicrobials tested (ampicillin, ciprofloxacin, clindamycin, doxycycline, oxacillin and trimethoprim/sulfamethoxazole). The most promising drug combination (doxycycline-carprofen) was further assessed by checkerboard testing extended to four additional MRSP strains belonging to ST71 or ST68, and by growth inhibition experiments.Seven non-antimicrobial drugs (bromhexine, acepromazine, amitriptyline, clomipramine, carprofen, fluoxetine and ketoconazole) displayed minimum inhibitory concentrations (MICs) ranging between 32 and >4096 mg/L, and enhanced antimicrobial activity of one or more antimicrobials. Secondary screening by checkerboard assay revealed a synergistic antimicrobial effect between carprofen and doxycycline, with the sum of the fractional inhibitory concentration indexes (ΣFICI) ranging between 0.3 and 0.5 depending on drug concentration. Checkerboard testing of multiple MRSP strains revealed a clear association between synergy and carriage of tetK, which is a typical feature of MRSP ST71. An increased growth inhibition was observed when MRSP ST71 cells in exponential phase were exposed to 0.5/32 mg/L of doxycycline/carprofen compared to individual drug exposure.ConclusionsCarprofen restores in vitro susceptibility to doxycycline in S. pseudintermedius strains carrying tetK such as MRSP ST71. Further research is warranted to elucidate the molecular mechanism behind the identified synergy and its linkage to tetK.

show abstract

Can We Prevent Antimicrobial Resistance by Using Antimicrobials Better?

Cited by 31 publications

References 82 publications

Synergistic activity profile of an antimicrobial peptide against multidrug‐resistant and extensively drug‐resistant strains of Gram‐negative bacterial pathogens

Synergistic activity profile of an antimicrobial peptide against multidrug‐resistant and extensively drug‐resistant strains of Gram‐negative bacterial pathogens

Knowledge, attitudes and practices towards antibiotic use in upper respiratory tract infections among patients seeking primary health care in Singapore

Antimicrobial synergy between carprofen and doxycycline against methicillin-resistant Staphylococcus pseudintermedius ST71

Contact Info

Product

Resources

About