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Revista de Gastroenterología de México. 2016;81(1):3---10
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REVISTA DEGASTROENTEROLOGIA
DE MEXICO´
´
ORIGINAL ARTICLE
Susceptibility to rifaximin and other antimicrobialagents of bacteria isolated from acute gastrointestinalinfections in Mexico�,��
O. Novoa-Faríasa, A.C. Frati-Munarib,∗, M.A. Peredoc, S. Flores-Juáreza,O. Novoa-Garcíaa, J. Galicia-Tapiaa, C.E. Romero-Carpioa
a División de Microbiología Clínica, Unidad de Diagnóstico Microbiológico UDMSC, Mexico City, Mexicob Departamento de Medicina Interna, Hospital Médica Sur, Mexico City, Mexicoc Alliance for the prudent use of antibiotics (APUA), Chapter Mexico, Mexico City, Mexico
Received 23 April 2015; accepted 14 July 2015Available online 1 February 2016
KEYWORDSRifaximin;Bacterial resistance;Bacterialsusceptibility;Antibiotics;Gastroenteritis;Small intestinalbacterial overgrowth
AbstractBackground: Bacterial resistance may hamper the antimicrobial management of acute gastroen-teritis. Bacterial susceptibility to rifaximin, an antibiotic that achieves high fecal concentrations(up to 8,000 �g/g), has not been evaluated in Mexico.Objective: To determine the susceptibility to rifaximin and other antimicrobial agents ofenteropathogenic bacteria isolated from patients with acute gastroenteritis in Mexico.Material and methods: Bacterial strains were analyzed in stool samples from 1,000 patientswith diagnosis of acute gastroenteritis. The susceptibility to rifaximin (RIF) was tested bymicrodilution (< 100, < 200, < 400 and < 800 �g/ml) and susceptibility to chloramphenicol (CHL),trimethoprim-sulfamethoxazole (T-S), neomycin (NEO), furazolidone (FUR), fosfomycin (FOS),ampicillin (AMP) and ciprofloxacin (CIP) was tested by agar diffusion at the concentrationsrecommended by the Clinical & Laboratory Standards Institute and the American Society forMicrobiology.Results: Isolated bacteria were: enteropathogenic Escherichia coli (E. coli) (EPEC) 531, Shigella120, non-Typhi Salmonella 117, Aeromonas spp. 80, enterotoxigenic E. coli (ETEC) 54, Yersinia
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enterocolitica 20, Campylobacter jejuni 20, Vibrio spp. 20, Plesiomonas shigelloides 20, andenterohemorrhagic E. coli (EHEC 0:157) 18. The overall cumulative susceptibility to RIF at<100, <200, <400, and <800 �g/ml was 70.6, 90.8, 99.3, and 100%, respectively. The overallsusceptibility to each antibiotic was: AMP 32.2%, T-S 53.6%, NEO 54.1%, FUR 64.7%, CIP 67.3%,
� Please cite this article as: Novoa-Farías O, Frati-Munari AC, Peredo MA, Flores-Juárez S, Novoa-García O, Galicia-Tapia J, et al. Suscepti-bilidad de las bacterias aisladas de infecciones gastrointestinales agudas a la rifaximina y otros agentes antimicrobianos en México. Revistade Gastroenterología de México. 2016;81:3---10.
�� See related content at doi: http://dx.doi.org/10.1016/j.rgmx.2016.01.001, Remes Troche JM. Reflexiones sobre la resistencia a
antibióticos y qué hacer al respecto. Rev Gastroenterol Méx. 2016;81(1):1---2.∗ Corresponding author. Alfa Wassermann S.A. de C.V., Av. Insurgentes Sur 2453-501, Col. Tizapán San Ángel. Del Álvaro Obregón, MéxicoD.F., CP 01090. México. Tel.:+5481 4707.
E-mail addresses: [email protected], [email protected] (A.C. Frati-Munari).
2255-534X/© 2015 Asociación Mexicana de Gastroenterología. Published by Masson Doyma México S.A. This is an open access article underthe CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
4 O. Novoa-Farías et al.
CLO 73%, and FOS 81.3%. The susceptibility to RIF <400 and RIF <800 �g/ml was significantlygreater than with the other antibiotics (p < 0.001).Conclusions: Resistance of enteropathogenic bacteria to various antibiotics used in gastroin-testinal infections is high. Rifaximin was active against 99-100% of these enteropathogens atreachable concentrations in the intestine with the recommended dose.© 2015 Asociación Mexicana de Gastroenterología. Published by Masson Doyma México S.A.This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
PALABRAS CLAVERifaximina;Resistenciabacteriana;Susceptibilidadbacteriana;Antibióticos;Gastroenteritis;Sobrepoblaciónbacteriana intestinal
Susceptibilidad de las bacterias aisladas de infecciones gastrointestinales agudas a larifaximina y otros agentes antimicrobianos en México
ResumenAntecedentes: La resistencia bacteriana puede dificultar el tratamiento antimicrobiano de lasgastroenteritis agudas. La susceptibilidad bacteriana de los enteropatógenos a la rifaximina,un antibiótico que alcanza altas concentraciones fecales (hasta 8,000 �g/g) no se ha evaluadoen México.Objetivos: Determinar la susceptibilidad a rifaximina y a otros antimicrobianos de bacteriasenteropatógenas aisladas de pacientes con gastroenteritis aguda en México.Material y métodos: Se analizaron las cepas bacterianas en las heces de 1,000 pacientescon diagnóstico de gastroenteritis aguda. Se probó la susceptibilidad a la rifaximina (RIF)con microdilución (< 100, < 200, < 400 y < 800 �g/ml), la susceptibilidad a cloranfenicol(CLO), trimetoprim-sulfametoxazol (T-S), neomicina (NEO), furazolidona (FUR), fosfomicina(FOS), ampicilina (AMP) y ciprofloxacino (CIP) se probó por difusión-agar a las concentracionesrecomendadas por CLSI y ASM.Resultados: Las bacterias aisladas fueron: Escherichia coli (E. coli) enteropatógena (EPEC) 531,Shigella 120, Salmonella no-typhi 117, Aeromonas spp. 80, E. coli enterotoxigénica 54, Yersiniaenterocolitica 20, Campylobacter jejuni 20, Vibrio spp. 20, Pleisiomonas shigelloides 20 y E. colienterohemorrágica (EHEC 0:157) 18. La susceptibilidad global acumulada a RIF < 100, < 200,< 400, < 800 �g/ml fue del 70.6, el 90.8, el 99.3 y el 100%, respectivamente. La susceptibilidadglobal a cada antibiótico fue: AMP 32.2%, T-S 53.6%, NEO 54.1%, FUR 64.7%, CIP 67.3%, CLO73%, FOS 81.3%. La susceptibilidad a RIF < 400 y < 800 �g/ml fue significativamente mayor quecon los otros antimicrobianos (p < 0.001).Conclusiones: La resistencia de las bacterias enteropatógenas a antimicrobianos utilizados engastroenteritis es alta. La rifaximina fue activa contra el 99-100% de las bacterias en concen-traciones alcanzables en el contenido intestinal con las dosis recomendadas.© 2015 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A.Este es un artículo Open Access bajo la licencia CC BY-NC-ND (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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cute diarrhea is an important health problem, mainly inhe developing countries. Despite the decrease in mortal-ty rates from this disease in the last decade in variousountries, including Mexico1---3, acute gastroenteritis contin-es to be a health problem due to its high morbidity. Inexico, it is the second most common infectious disease,nly preceded by respiratory diseases, with more than 5illion new cases per year4.Despite the presence of certain clinical signs, it is dif-
cult to determine the causal agent of acute diarrhea
n a patient based solely on clinical findings. Acute gas-roenteritis is often due to a viral infection, especially inhildren under 5 years of age1, whereas bacterial infec-ion is more habitual in older children and adults. Theapai
ost frequently detected enteropathogenic bacteria inatients with endemic gastroenteritis are Escherichia coliE. coli) (EPEC, EIEC, EHEC, ETEC), Campylobacterejuni (C. jejuni), Shigella spp, Salmonella spp, Yersinianterocolitica (Y. enterocolitica)5---8, and less frequently,eromonas spp, Vibrios spp9---12, and Pleisomonas shigeloidesP. shigeloides)13---15. The number of cases vary in relation toeographic region, patient age, and the season of the yearn which the study was conducted.
The aims of therapeutic management of patientsffected with gastroenteritis are to preserve life, relieveymptoms, prevent complications, cut the disease short,
nd prevent the spread of the pathogenic agents to theopulation. Oral rehydration is the standard treatment incute gastroenteritis and antimicrobial agents are indicatedn severe or prolonged cases, when shigellosis or cholera
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Susceptibility of bacteria isolated from acute gastrointestin
are suspected, or when the pathogen is known, in orderto prevent contagion16. However, in daily clinical practice,when the result of the stool culture is reported, the patientis already recovering or the treatment is delayed. Know-ing the susceptibility of the bacteria causing a syndrometo the antimicrobial agents is important in 2 aspects: oneis the early therapeutic approach, out of empirical neces-sity, and the other is the epidemiologic surveillance ofbacterial resistance that is useful for taking measures toprevent it.
The empirical use of antimicrobials can be inefficientdue to the emergence of bacterial resistance. Thereforethe possible therapeutic regimens should be frequentlyupdated, taking the pattern of regional resistance intoaccount17---20. Some clinical studies indicate that quinolonesare superior to other antibiotics or to placebo in the empir-ical treatment of adult patients with diarrhea17,20---22. Otherantimicrobial drugs, such as ampicillin (AMP), trimethoprim-sulfamethoxazole (T-S), chloramphenicol (CHL), furazoli-done (FUR), and non-absorbable antibiotics, such asneomycin and recently rifaximin (RIF), have been used inchildren, in whom quinolones are not indicated, and alsoin adults17,23---25. Nevertheless, recent data on the bacterialsusceptibility to these antimicrobial agents is not availablein Mexico. RIF is a semisynthetic antibiotic derived frombroad spectrum rifamycin S that inhibits the synthesis ofbacterial RNA, is not absorbable when taken orally, andreaches a very high concentration in the intestinal lumen(∼8,000 �g/g of feces). It has excellent bactericide activ-ity on enteropathogenic microorganisms and does not causeimportant alterations in the gut microbiota26.
The aim of this study was to investigate the susceptibil-ity of the acute gastroenteritis-causing bacteria to rifaximinand the most widely used antibiotics in the treatment ofgastrointestinal infections in Mexico.
Atf
Table 1 Bacteria isolated from 1,000 patients diagnosed with ac
Bacteria Number Serotypes invo
EnteropathogenicE. coli groupA,B, and C
531 O127:B8, O111O119:B4, O128O142:B86, O11should corresp
Enterotoxigenic (LT) E. coli 54 Only thermolabEnterohemorrhagic E. coli 18 Only O:157 serShigella dysenteriae 54 All the serotypShigella flexneri 24 All the serotypShigella boydii 27 All the serotypShigella sonnei 15 All the serotypSalmonella Group A 24 Most likely speSalmonella Group B 21 Most likely speSalmonella Group C1 24 Most likely speSalmonella Group C2 24 Most likely speSalmonella Group D 24 Most likely speVibrio spp. 20 ---Yersinia enterocolitica 20 ---Campylobacter jejuni 20 ---Pleisomonas shigeloides 20 ---Aeromonas 80 ---
fections 5
ethods
acterial isolations
acterial strains obtained from the stool samples of,000 patients diagnosed with gastroenteritis or acute diar-hea were analyzed in 10 hospital laboratories in Mexicoity that attend to hospitalized patients and outpatients.he strains were conserved and frozen before carrying outhe biochemical identification, serology, and the antimicro-ial susceptibility test in milk broth and soy broth withlycerol at −70 ◦C;27 the initial primary isolations from thetool samples were carried out at each particular labora-ory, and the following culture media were used: MacConkeygar, Sorbitol-MacConkey Agar, Salmonella Shigella Agar,LD Agar, Campylobacter Agar, Yersinia Agar, TCBS Agar,rilliant Green Agar, and Tetrathionate Broth28.
The isolates were biochemically identified in eachaboratory using AutoScan 4, Walkaway (MicroScan), oritek 2 (Biomeriux) manual and automated processes andystems29---31 with an acceptance probability > 95% in thedentification; the typing and serologic identification inetermined bacterial species, such as E. coli, Salmonella,nd Shigella, were then performed using the Bio-Rad32,hadebact33, Oxoid34, Sanofi-Pasteur35, ‘‘O’’ Beli36, androbac37 specific antisera and agglutination or coagglutina-ion reagents. The detected serogroups and serotypes arehown in Table 1.
ntimicrobial agents and susceptibility tests
ntimicrobial susceptibility testing (AST) was done throughhe agar diffusion method (CHL, T-S, neomycin [NEO], FUR,osfomycin [FOS], AMP, and ciprofloxacin [CIP]), and by
ute gastroenteritis and their serotypes.
lved
:B4, O55:B5, O26:B6 and other serotypes:B12, O124:B17, O86:B7, O126:b16 and other serotypes9:K90, O124:B17, O86:B7, O126:B16 and other serotypes thatond to: O128:K73, O44:K74, O18:K77, O20:K61, and O20:K84ile (TL) toxin-producing serotypes
otypees that are agglutinable with the specific antiserumes agglutinable with the specific antiserumes that are agglutinable with the specific antiserumes that are agglutinable with the specific antiserumcies: S.paratyphicies: S.typhimuriumcies: S.choleraesuiscies: S.newportcies: S.enteritidis
6 O. Novoa-Farías et al.
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800
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600
500
400
300
200
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Figure 1 Overall accumulated susceptibility of the isolatedbacteria to rifaximin. In the 1,000 strains, RIF was tested ata concentration of 100 �g/ml. The bacteria that were notsusceptible at that concentration were successively exposedto concentrations of 200 �g/ml, 400 �g/ml, and 800 �g/ml. Thea9
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icrodilution (RIF) following the recommendations of thelinical & Laboratory Standards Institute38 and the Amer-
can Society for Microbiology39. The concentrations of thentibiotics assayed and AST conditions were: AMP 10 �g/ml,-S 1.25/23.75 �g/ml, CHL 30 �g/ml, CIP 5 �g/ml, FUR00 �g/ml, NEO 30 �g/ml, FOS 50 �g/ml. RIF was tested at00 �g/ml and the strains that were not susceptible at thisoncentration were successively exposed to concentrationsf 200 �g/ml, 400 �g/ml, and 800 �g/ml. Susceptibility toIF was considered at a minimal inhibitory concentrationMIC) of MIC100, whereas it was MIC90 for the other antibi-tics.
tatistical analysis
acterial susceptibility to RIF was compared with the sus-eptibility to the other antimicrobial agents with the Z testnd statistical significance was set at a p < 0.05. The Statis-ica 8.0 and Stata 11 statistical software were employed.
esults
he stool samples from 511 men and 489 women were ana-yzed. Sixty-five percent of the participants were above0 years of age. The isolated bacteria were E. coli 603 (EPEC31, ETEC 54, EHEC 18), Shigella 120 (dysenteriae, flexneri,oydii, sonnei), Salmonella 117 (paratyphi, typhimurium,holeraesuis, newport, enteritidis), Vibrio spp. 20, Y. ente-ocolitica 20, C. jejuni 20, P. shigeloides 20, and Aeromonaspp. 80.
Overall susceptibility of the bacteria to the differentoncentrations of RIF (MIC100) are shown in Figure 1. Theesults of accumulated susceptibility patterns in all thetrains assayed were at < 100 �g/ml: 70.6%; at < 200 �g/ml:0.8%; at < 400 �g/ml: 99.3%; and at < 800 �g/ml: 100.0%.able 2 shows the susceptibility of each group of bacte-ia to the different RIF concentrations. More than 99% ofhe strains of Shigella, Salmonella, Yersinia, Campylobac-er, Vibrio, Pleisiomonas, and Aeromonas were susceptible
o concentrations < 100 or < 200 �g/ml, whereas 11-15% ofhe E. coli required < 400 or even < 800 �g/ml.Overall susceptibility of all the bacterial species to eachntibiotic was: RIF (< 400 �g/ml) 99.3% and (< 800 �g/ml)
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Table 2 Susceptibility of the bacteria to different concentration
Bacteria Number < 100 �g/ml
EPEC 531 58.95
ETEC 54 79.63
EHEC 18 72.22
Shigella 120 90.00
Salmonella 117 67.52
Yersinia 20 80.00
Campylobacter 20 70.00
Vibrio 20 100.00
Plesiomonas 20 100.00
Aeromonas 80 100.00
All 1000 70.6
Results expressed in % of susceptible strains.
ccumulated susceptible strains were 706 (< 100), 908 (< 200),93 (< 400), and 1,000 (< 800).
00%, FOS 81.3%, CHL 73.0%, CIP 67.3%, FUR 64.7%, NEO4.1%, T-S 53.6%, and AMP 32.2%. Overall susceptibility toIF with < 400 and < 800 �g/ml was superior (p < 0.001)o the overall susceptibility to each of the 8 drugs studiedfig. 2). This was also true in the majority of the cases inach bacterial group alone.
Table 3 shows the susceptibility of each bacterial groupo the antibiotics tested.
As can be seen, a large number of strains show a veryigh proportion of bacterial resistance to NEO, T-S, and AMP,ut Yersinia continues to be very susceptible to AMP (100%),ibrio to T-S (90%), and Campylobacter to NEO.
iscussion
he prevalence and incidence of the bacteria that cause
astroenteritis worldwide vary according to the type ofopulation studied, the geographic location of the study,he season of the year in which the microbiologic diag-osis is made, and other clinical and sociodemographics of rifaximin.
< 200 �g/ml < 400 �g/ml < 800 �g/ml
25.61 14.69 0.757.41 7.41 5.56
16.67 11.11 ---10.00 --- ---31.62 0.85 ---20.00 --- ---30.00 --- ------ --- ------ --- ------ --- ---
20.2 8.5 0.7
Susceptibility of bacteria isolated from acute gastrointestinal in
99.3
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RIF FOS CHL CIP FUR NEO T-S AMP
100
90
80
70
60
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40
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Figure 2 Overall susceptibility of the 1,000 isolated bacterialstrains to the different antibiotics.Rifaximin vs the other antimicrobials p < 0.0001.AMP: ampicillin; CHL: chloramphenicol; CIP: ciprofloxacin; FOS:
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fosfomycin; FUR: furazolidone; NEO: neomycin; RIF: rifaximin(< 400 �g/ml); T-S: trimethoprim-sulfamethoxazole.
characteristics of the patients studied6,40---42. Even thoughours was not a prevalence study, the strains were collectedthroughout the entire year of 2013 and therefore the sea-sonal variations were not influential. The frequency of thestrains received in the clinical analysis laboratories wasreflected and the dominating ones were E. coli, Shigella,Salmonella, and Aeromonas. These data coincide with otherreports in Mexico23,43,44.
Standards for defining susceptibility or bacterial resis-tance have been published for the majority of antibiotics38.Nevertheless, there are no clinical cut-off points forrifamycins against enteropathogens, although a value of≤ 32 �g/ml of rifaximin was applied by some researchers intraveler’s diarrhea45---47. Bacterial susceptibility to an antibi-otic implies that the isolations are inhibited by the usuallyachievable concentration of the antimicrobial agent at theinfection site when the recommended dose is used. Fecal
concentrations of rifaximin have been reported of up to8,000 �g/g (mean 7,961 �g/g) after 3 days of treatment atthe recommended dose of 800 mg/day, and there were stillmean fecal concentrations of 3,266 �g/g 3 days after theftsw
Table 3 Susceptibility of each group of bacteria to the antimicro
Group of bacteria FOS CHL CIP
EPEC 7.1 66.6 51.9
ETEC 75.9 88.8 50.0
EHEC 55.5 83.3 100
Shigella 68.3 82.5 97.5
Salmonella 77.8 64.1 89.7
Yersinia 90.0 80.0 90.0
Campylobacter 80.0 95.0 30.0
Vibrio 90.0 80.0 100
Plesiomonas 100 95.0 80.0
Aeromonas 67.5 86.0 87.5
All 81.3 73.0 67.3
Results expressed in % of susceptible strains.
fections 7
nd of the therapy48. In our study, we evaluated the sus-eptibility to rifaximin at 4 concentrations: < 100, < 200,
400, and < 800 �g/ml. The general susceptibility observedt these concentrations implies a certain bacterial resis-ance to rifaximin at concentrations of < 100 �g/ml that wasvercome at higher concentrations, but always much belowhe achievable values in the intestinal lumen. The cut-offoints for considering bacteria to be resistant to rifaximinave been established at 32, 128, or even 256 �g/ml46---49,ut, as observed in our study, the bacteria resistant to loweroncentrations of rifaximin were not resistant if the concen-ration of the antibiotic was increased in vitro. Finally, 99.3%ere susceptible at concentrations < 400 �g/ml and 100%t concentrations < 800 �g/ml, which are 10-20 times lowerhan the mean concentration achieved in vivo with the rec-mmended treatment.
The concentrations in the intestinal lumen, or fecal con-entrations, of the other antimicrobial agents tested in theresent study are not known, so the internationally rec-mmended concentrations were used for the susceptibilitynalysis. In general, the bacteria were more susceptible toifaximin than to the other antimicrobial agents tested in ournalysis. Recent studies with enteropathogen isolates fromravelers coming from Latin America and Asia also found areater proportion of bacteria susceptible to rifaximin thano other antimicrobial agents. It was striking that the C.ejuni strains from Asia had a variable resistance to rifax-min, whereas those from Mexico and Guatemala were 100%usceptible46,47. In our study, the C. jejuni strains were00% susceptible at concentrations of < 100-200 �g/ml. Sev-ral strains of E. coli required rifaximin concentrationsreater than 100 �g/ml, concurring with other observationsn bacteria coming from Mexico50.
Rifaximin has a broad spectrum of susceptibility thatncludes anaerobic bacteria26,49. Bacterial resistance is veryow and is not easily induced51. In addition, Ouyang---Latimert al. compared the susceptibility of enteropathogenicacteria obtained in 2006-2008 with those obtained0 years earlier and found no increase in the MIC90 lev-ls for rifaximin in any of the organisms analyzed46. In
act, the normal intestinal bacteria that became resis-ant to 100 �g/ml of rifaximin after 5 days of treatmentpontaneously disappeared from the stools within a feweeks52.bials tested.
FUR NEO T-S AMP
66.4 48.5 49.1 27.677.7 53.7 50.0 29.650.0 61.1 16.6 16.647.5 46.6 27.5 48.364.1 52.1 74.4 50.480.0 30.0 2.5 100
100 100 30.0 45.090.0 70.0 90.0 55.085.0 90.0 90.0 20.050.0 80.0 78.7 20.064---7 54.1 53.6 32.2
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The low proportion of bacteria that are susceptible toMP, T-S, neomycin, FUR, and CIP, from 32.2 to 67.3% in thatrder, coincides with studies conducted in other regions ofhe world53---56 and can be explained by the induction of bac-erial resistance due to the widespread use or abuse of thosentimicrobial agents. In this respect, it is striking that CHL,hich conserves an acceptable general susceptibility of 73%,as been restricted, after its widespread use in Mexico, toreating typhoid fever for the last 30 years. And compara-ively, in our study we introduced the test of susceptibility toOS. This antibiotic is used very little in Mexico, and mainlyn urinary infections. The general susceptibility of FOS wasreater than that of the other antimicrobial agents, justelow rifaximin.
Neomycin is a poorly absorbed antibiotic that is widelysed in Mexico and does not require a prescription. Accord-ng to our data, it is clear that AMP, T-S, neomycin, andUR would not be good therapeutic options. RIF has beenuccessfully used for treating acute infectious diarrhea inhildren and adults, as well as for traveler’s diarrhea, withxcellent tolerance57---60. RIF would appear to be the bestption, given that it has a high therapeutic index, com-ining high efficaciousness with a low frequency of adverseffects26. Adverse effects are frequently attributed to otherntibiotics, especially to beta-lactams and T-S mainly dueo allergies, and the sulfonamides and CIP are known to beeurotoxic61.
Treatment with antimicrobial agents is a valuable tooln the control of several gastrointestinal infections, givenhat the length of time and intensity of the disease iseduced, potentially severe complications are prevented,nd disease transmission is decreased. Unfortunately, foreveral decades, enteropathogenic bacteria strains haveeen selected that are resistant to the commonly usedntimicrobial agents and to those that once were consideredrst choice62. The selection and dissemination of antimicro-ial resistance among the different bacterial species thatause gastroenteritis is a growing health problem that com-licates the therapeutic management of the severe cases.tudies conducted in many parts of the world have revealedn important increase in antimicrobial-resistant bacteria inany infectious diseases, including gastroenteritis63,64. To
educe the appearance of antimicrobial-resistant bacterialtrains, it would seem prudent to avoid the indiscriminatese of antibiotics in cattle, periodically determine localacterial resistance patterns, reduce the easy access tontimicrobial drugs (for example: prevent self-medicationith antimicrobials), and strengthen the medical educationn this topic.
Study limitations. The stool cultures were obtainedrom 10 laboratories that sent positive stool culturesith enteropathogen bacteria from patients diagnosed withcute gastroenteritis or acute diarrhea. Therefore, it wasot possible to obtain the clinical data, such as the lengthf time of symptom progression, stool characteristics, theymptoms accompanying the diarrhea, and the intensityr severity of the clinical symptoms that would enableheir correlation with the genus and species of the bac-
erial isolates. The stool cultures were from Mexico Citynd do not necessarily reflect those from the rest of theountry.1
O. Novoa-Farías et al.
thical responsibilities
rotection of persons and animals. The authors declarehat no experiments were performed on humans or animalsor this study.
ata confidentiality. The authors declare that no patientata appear in this article.
ight to privacy and informed consent. The authorseclare that no patient data appear in this article.
inancial disclosure
his study was financially supported by Alfa Wassermann S.A.e C.V.
onflict of interest
lberto Frati is presently the medical director of Alfaassermann S.A. de C.V., which produces rifaximin. He par-
icipated in the planning of the project and manuscriptevision, but did not intervene in any phase of the study, thenumeration of the results, or the statistical analysis. Thether authors declare that there is no conflict of interest.
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