Effects of Ampicillin, Gentamicin, and Cefotaxime on the Release of Shiga Toxins from Shiga Toxin–ProducingEscherichia coliIsolated During a Diarrhea Episode in Faisalabad, Pakistan

Abstract

The Shiga toxin-producing Escherichia coli (STEC) is an emerging foodborne pathogen. The proportion of cases attributed to STEC in an episode of diarrhea in the Faisalabad region of Pakistan was investigated. In addition, as increase in Shiga toxin (Stx) release after exposure to various antimicrobial agents is widely reported, we also elucidated the in vitro effects of three commonly used antibiotics (ampicillin, gentamicin, and cefotaxime) on Stx release. Isolation and detection of STEC was done using enzyme-linked immunosorbent assay and polymerase chain reaction, followed by phenotypic characterization. In vitro Stx release from isolated STEC was determined using enzyme-linked immunosorbent assay, and Stx-induced verocytotoxicity was quantified using cytotoxicity detection assay. STEC was detected in 5 (21.7%) of 23 patients. Exposure to minimum inhibitory concentration (MIC) of ampicillin, gentamicin, and cefotaxime resulted in a considerable decrease in toxin release and level of cytotoxicity in most of the STEC isolates when compared with control (without antibiotic exposure). Exposure to sub-MIC of ampicillin resulted in a relative increase in Stx release and cytotoxicity (p <or= 0.05) in three of the four isolates tested, whereas a decreasing trend was observed in isolates exposed to sub-MICs of gentamicin and cefotaxime. Sub-MIC of gentamicin resulted in largest decrease in Stx release and a similar trend was observed with cefotaxime to a lesser extent. In conclusion, these in vitro observations suggested that sub-MIC of ampicillin may stimulate Stx release and level of cytotoxicity and therefore should be avoided. Gentamicin did not show such effects and therefore may be considered for STEC antimicrobial therapy.

Phenethyl Isothiocyanate Inhibits Shiga Toxin Production in Enterohemorrhagic Escherichia coli by Stringent Response Induction

“…Moreover, in similar experiments, some antibiotics (e.g., rifaximin, gentamicin, cefotaxime, fosfomycin, and kanamycin) were found to decrease, rather than increase, the toxin production (43,44). The effects of some antibiotics were strongly dependent on their concentrations, causing either an increase or decrease in efficiency of Shiga toxin production (44)(45)(46). In this light, it is important to note that it was reported recently that STEC strain O104:H4, which caused a recent outbreak in Germany, did not release Shiga toxin in response to therapeutic concentrations of ciprofloxacin, meropenem, fosfomycin, and chloramphenicol (47).…”

“…Although increased production of Shiga toxins has been demonstrated after antibiotic treatment of STEC strains cultured under laboratory conditions (reviewed in references 17, 20, 22, and 23), it is worth noting that the vast majority of such experiments were performed with the use of subinhibitory concentrations. For example, concentrations between 1/2 and 1/64 MIC were used to demonstrate enhanced stx gene expression and/or release of Shiga toxins following addition of norfloxacin, ciprofloxacin, ampicillin, levofloxacin, streptomycin, chloramphenicol, and erythromycin (42)(43)(44)(45)(46). Moreover, in similar experiments, some antibiotics (e.g., rifaximin, gentamicin, cefotaxime, fosfomycin, and kanamycin) were found to decrease, rather than increase, the toxin production (43,44).…”

“…For example, concentrations between 1/2 and 1/64 MIC were used to demonstrate enhanced stx gene expression and/or release of Shiga toxins following addition of norfloxacin, ciprofloxacin, ampicillin, levofloxacin, streptomycin, chloramphenicol, and erythromycin (42)(43)(44)(45)(46). Moreover, in similar experiments, some antibiotics (e.g., rifaximin, gentamicin, cefotaxime, fosfomycin, and kanamycin) were found to decrease, rather than increase, the toxin production (43,44). The effects of some antibiotics were strongly dependent on their concentrations, causing either an increase or decrease in efficiency of Shiga toxin production (44)(45)(46).…”

Different Effects of Six Antibiotics and Ten Traditional Chinese Medicines on Shiga Toxin Expression byEscherichia coliO157:H7

“…Other studies [17, 19] have shown that cefotaxime and meropenem [44] do not affect stx gene expression. By contrast, it was reported [17, 18] that ampicillin increased stx gene expression. However, the present study showed that cefotaxime had little inductive effect on stx 2 gene expression.…”

Role of antimicrobials in the treatment of adult patients presenting to the emergency department with acute gastroenteritis - A mini review

“…At least one study in vitro showed that gentamycin may safely reduce the release of shiga toxin (Stx) from Shiga toxin producing E. coli , but evidence is lacking to recommend the use of this antibiotic in most cases 17. If antibiotics must be given, an animal study suggests that macrolides, such as azithromycin, may also be a safer option 18.…”