Faculty Opinions recommendation of Impact of extensive antibiotic treatment on faecal carriage of antibiotic-resistant enterobacteria in children in a low resistance prevalence setting.

The anaerobic pathogen Clostridium difficile is of growing significance for the health care system due to its increasing incidence and mortality. As C. difficile infection is both supported and treated by antibiotics, a deeper knowledge on how antimicrobial agents affect the physiology of this important pathogen may help to understand and prevent the development and spreading of antibiotic resistant strains. As the proteomic response of a cell to stress aims at counteracting the harmful effects of this stress, it can be expected that the pattern of a pathogen’s responses to antibiotic treatment will be dependent on the antibiotic mechanism of action. Hence, every antibiotic treatment is expected to result in a specific proteomic signature characterizing its mode of action. In the study presented here, the proteomic response of C. difficile 630∆erm to vancomycin, metronidazole, and fidaxomicin stress was investigated on the level of protein abundance and protein synthesis based on 2D PAGE. The quantification of 425 proteins of C. difficile allowed the deduction of proteomic signatures specific for each drug treatment. Indeed, these proteomic signatures indicate very specific cellular responses to each antibiotic with only little overlap of the responses. Whereas signature proteins for vancomycin stress fulfil various cellular functions, the proteomic signature of metronidazole stress is characterized by alterations of proteins involved in protein biosynthesis and protein degradation as well as in DNA replication, recombination, and repair. In contrast, proteins differentially expressed after fidaxomicin treatment can be assigned to amino acid biosynthesis, transcription, cell motility, and the cell envelope functions. Notably, the data provided by this study hint also at so far unknown antibiotic detoxification mechanisms.

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Transmission of infectious drug resistance from animals to man

Journal of Hygiene ◽

10.1017/s0022172400046374 ◽

1973 ◽

Vol 71 (1) ◽

pp. 209-215 ◽

Cited By ~ 22

Author(s):

D. M. Wells ◽

O. B. James

Keyword(s):

Drug Resistance ◽

Antibiotic Resistance ◽

Antibiotic Treatment ◽

Farm Animals ◽

Antibiotic Resistant ◽

R Factor ◽

Resistance Patterns ◽

Antibiotic Resistance Patterns ◽

R Factors

SUMMARYThe antibiotic resistance patterns of coliforms in faecal specimens from pigs and their human contacts were studied. The ability of the resistant coliforms to transfer their resistance in vitro to antibiotic-sensitive recipients was examined. The results showed that pigs which had received antibiotics carried more multiply-resistant, R-factor bearing coliforms than pigs which had not been given antibiotics. Human contacts of the antibiotic-treated pigs had a higher incidence of antibiotic-resistant coliforms with R-factors than human contacts of pigs which had not been given antibiotics. It is concluded that antibiotic treatment of farm, animals may lead to acquisition of antibiotic resistance by gut coliforms of man.

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Antibiotic resistant staphylococci acquired during the first year of life

Journal of Hygiene ◽

10.1017/s0022172400053821 ◽

1978 ◽

Vol 81 (1) ◽

pp. 125-130 ◽

Cited By ~ 7

Author(s):

M. L. Burr ◽

C. H. L. Howells ◽

P. W. J. Rees

Keyword(s):

Staphylococcus Aureus ◽

Antibiotic Treatment ◽

First Year ◽

Antibiotic Resistant ◽

South Wales ◽

Maternity Hospitals ◽

Nasal Swabs ◽

Resistant Strains ◽

Discharge From Hospital ◽

First Year Of Life

SUMMARYNasal swabs were taken from 492 babies born consecutively to residents of two South Wales towns soon after their discharge from maternity hospitals. Staphylococcus aureus was isolated from 352 babies (72%) and in 79 (22%) of these it was resistant to at least one antibiotic. By the time these babies were a year old the prevalence of both sensitive and resistant strains had fallen, so that only 12% still carried nasal staphylococci, but 64% of these organisms were then resistant to penicillin. Administration of penicillin to the baby seemed to be a more important factor in selecting resistant organisms than other antibiotics given to the baby, any antibiotic treatment to other members of the household, or discharge from hospital.

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Within-host competition modulates pneumococcal antibiotic resistance in the pre-vaccination era

10.1101/2020.09.24.311340 ◽

2020 ◽

Author(s):

José Lourenço ◽

Yair Daon ◽

Andrea Gori ◽

Uri Obolski

Keyword(s):

Antibiotic Resistance ◽

Antibiotic Treatment ◽

Host Population ◽

Pneumococcal Infections ◽

Evolutionary Mechanisms ◽

Antibiotic Resistant ◽

Country Level ◽

Modelling Framework ◽

Public Health Challenge ◽

Open Question

AbstractBackgroundAntibiotic treatment is a key tool in the fight against pneumococcal infections. However, the ongoing emergence of antibiotic resistant strains and high frequencies of antibiotic resistance of pneumococci pose a major public health challenge. How and which ecological and evolutionary mechanisms help maintain the coexistence of strains susceptible and resistant to antibiotic treatment remains largely an open question.Methods/resultsExpanding on a Streptococcus pneumoniae modelling framework, we here explore how both between- and within-host mechanisms of transmission can sustain observed levels of pneumococcal resistance to antibiotics in the pre-vaccination era using a stochastic, individual-based model. Our framework considers that within-host competition for co-colonization between resistant and susceptible strains can arise via pre-existing immunity (immunological competition) or intrinsic fitness differences due to resistance costs (ecological competition). We find that beyond stochasticity, host-population structure or movement at the between-host level, competition at the within-host level can explain observed variation in resistance frequencies.ConclusionIn a series of simulated scenarios informed by observed pneumococcal data in the European region, we demonstrate that ecological competition for co-colonization can explain much of the variation in co-existence observed at the country level in the pre-vaccination era. This work expands our understanding of how within-host pneumococcal competition facilitates the maintenance of antibiotic resistance in the pre-vaccination era. The demonstration of the effects of such underlying, often unmeasured competition-related components of pneumococcal dynamics improves our understanding of the mechanistic drivers for the emergence and maintenance of antibiotic resistance.

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Emergence of nosocomial associated opportunistic pathogens in the gut microbiome after antibiotic treatment

Antimicrobial Resistance and Infection Control ◽

10.1186/s13756-021-00903-0 ◽

2021 ◽

Vol 10 (1) ◽

Author(s):

Isaac Raplee ◽

Lacey Walker ◽

Lei Xu ◽

Anil Surathu ◽

Ashok Chockalingam ◽

...

Keyword(s):

Gut Microbiota ◽

Antibiotic Therapy ◽

Antibiotic Treatment ◽

Nosocomial Infections ◽

Pathogenic Bacteria ◽

Antibiotic Administration ◽

Oral Antibiotic ◽

Opportunistic Pathogens ◽

Taxonomic Assignment ◽

Antibiotic Resistant

Abstract Introduction According to the Centers for Disease Control’s 2015 Hospital Acquired Infection Hospital Prevalence Survey, 1 in 31 hospital patients was infected with at least one nosocomial pathogen while being treated for unrelated issues. Many studies associate antibiotic administration with nosocomial infection occurrence. However, to our knowledge, there is little to no direct evidence of antibiotic administration selecting for nosocomial opportunistic pathogens. Aim This study aims to confirm gut microbiota shifts in an animal model of antibiotic treatment to determine whether antibiotic use favors pathogenic bacteria. Methodology We utilized next-generation sequencing and in-house metagenomic assembly and taxonomic assignment pipelines on the fecal microbiota of a urinary tract infection mouse model with and without antibiotic treatment. Results Antibiotic therapy decreased the number of detectable species of bacteria by at least 20-fold. Furthermore, the gut microbiota of antibiotic treated mice had a significant increase of opportunistic pathogens that have been implicated in nosocomial infections, like Acinetobacter calcoaceticus/baumannii complex, Chlamydia abortus, Bacteroides fragilis, and Bacteroides thetaiotaomicron. Moreover, antibiotic treatment selected for antibiotic resistant gene enriched subpopulations for many of these opportunistic pathogens. Conclusions Oral antibiotic therapy may select for common opportunistic pathogens responsible for nosocomial infections. In this study opportunistic pathogens present after antibiotic therapy harbored more antibiotic resistant genes than populations of opportunistic pathogens before treatment. Our results demonstrate the effects of antibiotic therapy on induced dysbiosis and expansion of opportunistic pathogen populations and antibiotic resistant subpopulations of those pathogens. Follow-up studies with larger samples sizes and potentially controlled clinical investigations should be performed to confirm our findings.

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Effect of 4-Hexylresorcinol on the Efficiency of Antibiotic Treatment of Experimental Sepsis Caused by Antibiotic-Resistant Klebsiella pneumoniae Strain in Mice

Bulletin of Experimental Biology and Medicine ◽

10.1007/s10517-021-05249-6 ◽

2021 ◽

Vol 171 (4) ◽

pp. 458-460

Author(s):

I. G. Shemyakin ◽

O. Yu. Manzenyuk ◽

G. I. El’-Registan ◽

V. V. Firstova ◽

T. I. Kombarova ◽

...

Keyword(s):

Klebsiella Pneumoniae ◽

Antibiotic Treatment ◽

Experimental Sepsis ◽

Antibiotic Resistant

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Effect of Antibiotic Treatment Delay on Therapeutic Outcome of Experimental Acute Otitis Media Caused by Streptococcus pneumoniae Strains with Different Susceptibilities to Amoxicillin

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.48.3.860-866.2004 ◽

2004 ◽

Vol 48 (3) ◽

pp. 860-866 ◽

Cited By ~ 7

Author(s):

Araceli Parra ◽

Carmen Ponte ◽

Carlos Cenjor ◽

Carmen Martínez-Marín ◽

Francisco Soriano

Keyword(s):

Streptococcus Pneumoniae ◽

Otitis Media ◽

Antibiotic Treatment ◽

Acute Otitis Media ◽

Antibiotic Administration ◽

Bacterial Inoculation ◽

Antibiotic Resistant ◽

Selection Of ◽

Antibiotic Resistant Mutants

ABSTRACT The effect of delayed administration of amoxicillin on the course of acute otitis media (AOM) caused by two Streptococcus pneumoniae strains with different susceptibilities to amoxicillin (MICs of 0.016 and 1 μg/ml for strains A and B, respectively) was evaluated in the gerbil model. The organisms were inoculated by transbullar challenge into the middle ear, and antibiotic treatment was administered at various times thereafter. The bacteriological and clinical efficacies of treatment diminished significantly with the delay of antibiotic administration. The bacterial eradication rates when antibiotic treatment was started at 2, 5, 8, 18, and 21 h post-bacterial inoculation were different for both strains (95, 95, 90, 55, and 55% for strain A and 95, 95, 65, 10, and 0% for strain B). Results of further experiments using strain B with higher antibiotic doses and numbers of administrations and different follow-up times indicate that the failures observed with the delayed administration were not related to the bacterial burden, selection of antibiotic-resistant mutants, or inadequate pharmacodynamic parameters. Such failures may be related to the metabolic bacterial status. The delayed amoxicillin treatment of AOM caused by S. pneumoniae may lead to therapeutic failures, mainly when organisms with diminished antibiotic susceptibility are involved.

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Postexposure Administration of a Yersinia pestis Live Vaccine for Potentiation of Second-Line Antibiotic Treatment Against Pneumonic Plague

The Journal of Infectious Diseases ◽

10.1093/infdis/jiz260 ◽

2019 ◽

Vol 220 (7) ◽

pp. 1147-1151 ◽

Cited By ~ 2

Author(s):

Ayelet Zauberman ◽

David Gur ◽

Yinon Levy ◽

Moshe Aftalion ◽

Yaron Vagima ◽

...

Keyword(s):

Yersinia Pestis ◽

Antibiotic Treatment ◽

Second Line ◽

Proof Of Concept ◽

Antibiotic Resistant ◽

Pneumonic Plague ◽

Iron Sequestration ◽

Resistant Strains ◽

Respiratory Challenge ◽

Temporary Inhibition

Abstract Pneumonic plague, caused by Yersinia pestis, is a rapidly progressing contagious disease. In the plague mouse model, a single immunization with the EV76 live attenuated Y. pestis strain rapidly induced the expression of hemopexin and haptoglobin in the lung and serum, both of which are important in iron sequestration. Immunization against a concomitant lethal Y. pestis respiratory challenge was correlated with temporary inhibition of disease progression. Combining EV76-immunization and second-line antibiotic treatment, which are individually insufficient, led to a synergistic protective effect that represents a proof of concept for efficient combinational therapy in cases of infection with antibiotic-resistant strains.

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