Indian Journal of Pharmacy and Pharmacology

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Get Permission Saeed: In-vitro postantibiotic effect (PAE) of ciprofloxacin against different bacterial species


Introduction

Postantibiotic effect (PAE) is the continued suppression of bacterial growth after exposure of the bacteria to an antimicrobial agent and removal of this agent from the environment (Craig and Gudmundsson (1996)1 and MacKenzie and Gould (1993).2 The PAE was recognized as an important pharmacodynamic parameter (Craig and Gudmundsson, 1999)3 and it is a standard metric used to evaluate novel antibiotics (Beam et al, 1992).4 The postantibiotic effect (PAE) refers to the temporary suppression of bacterial growth following transient exposure to antibiotics. This transient inhibition has been observed since the first studies of penicillin against Pneumococcus and Streptococcus in the 1940s. Even after the antibiotic had been degraded by a penicillinase, the target populations exhibited a significant lag before resuming growth (Bigger, 1944 and Eagle and Fleischman, 1950).5

The term postantibiotic effect (PAE) refers to a period of time after complete removal of an antibiotic during which there is no growth of the target organism (Craig and Gudmundsson 1991).

The PAE appears to be a feature of most antimicrobial agents and has been documented with a variety of common bacterial pathogens. Several factors influence the presence or duration of the PAE including the type of organism, type of antimicrobial, concentration of antimicrobial, duration of antimicrobial exposure, and antimicrobial combinations.

In this study, the PAEs of ciprofloxacin against different species of bacteria were examined.

Materials and Methods

Bacterial strains

The bacterial cultures were supplied by the department of Microbiology, Faculty of veterinary Medicines, University of Khartoum. The bacterial species were: Pasteurella multocida, E. coli (isolated from urine), Salmonella duplin (reference strain NCTC 5766) and Staphylococcus aureus (isolated from rectal swab).

Figure 1

Induction of PAE by ciprofloxacin against (a) Salmonella dublin (b) Pasteurella multocida (c) Staphylococcus aureus (d) E. Coli (control, filled squires, antibiotic-exposed, open squires).

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All species in this study were identified according to Barrow and Feltham (2003)6 and also test kits (quick GN, NISSUI) were used for the identification of Gram-negative bacteria.

Antimicrobial agent

Ciprofloxacin was received as a dry laboratory powder and it was dissolved and obtained at concentration of 1μg/ml.

Growth curves

The growth (measured in log10 CFU/ml) for all species was performed in nutrient broth. Six tubes were labeled from time zero, 45minutes, 2 hours, 4 hours, 6 hours and 7 hours, the viable count was performed according to Miles and Misra (1938).7

PAE determinations

The growth curve of the control was compared with the curve of the organism after subjected to the antibiotic (ciprofloxacin). The control tubes and antibiotic-containing tubes were incubated at 37°C.

Results

The PAE durations of the ciprofloxacin in Figure 1. The longest PAE in this group was observed when using ciprofloxacin against Staphylococcus aureus (6 hours) and the shortest was against Pasteurella multocida (1–2 hours), whereas the PAE of ciprofloxacin was found to be 4 hours for Salmonella dublin. E. coli was found to be resistant to ciprofloxacin in all phases.

Discussion

The study of the delayed regrowth of surviving bacteria following cessation of antibiotic administration, the post-antibiotic effect (PAE), and related phenomena such as the integration of the pharmacological and antimicrobial profiles of drugs became known as pharmacodynamics and is increasingly being applied to the design of dose regimens (MacKenzie and Gould 1993).8

The results of this study were asserted with Chin and  Neu (1987)9 who’s mentioned that the ciprofloxacin produced an excellent PAE for most gram-negative bacteria and for S. aureus. The longest PAE in this study was observed when using ciprofloxacin against Staphylococcus aureus (6 hours). Also Licata, et al., (1997)10 found that a pronounced suppression of bacterial growth extending to 4.8 and 6.5 hours was seen with exposure to ciprofloxacin at one-eighth and one-fourth the MIC of ciprofloxacin for S.aureus.

Our results were confirmed by Schierholz et al. (1998)11 as they reported that antimicrobial agents are generally tested against bacteria in the log phase of multiplication to produce the maximal bactericidal effect. From the above results, in the log phase the bacterial cells are more fragile since they are dividing in an accelerated rate and this makes the cells of the bacteria more susceptible to antibiotics and they will be more susceptible to external environment.

The PAE for Salmonella dublin when it was subjected to an antibiotic (1µg /ml ciprofloxacin) was “2 hours” which represents the beginning of the log-phase. It was observed that at time “2 hours” the number of bacteria decreased and reached zero. Majtán  and Majtánová, (1997)12 was observed the longest PAE result with Salmnella typhimurium after treatment with ciprofloxacin in compared with other antibiotic.

Over the past three decades, quinolone resistance in Enterobacteriaceae from human and veterinary isolates has increased (Rodríguez-Martínez et al., 2016b).13 Therefore, this result supported our findings that the E. coli was found to be resistant to ciprofloxacin in all phases.

In the present study, the in-vitro PAEs of ciprofloxacin determination against different species of bacteria (Salmonella dublin, Pasteurella multusida and Staphylococcus aureus were found to be ranged between 1-6 hours for all species. The E.coli found to be resistant in all growth phases.

Source of Funding

None.

Conflict of Interest

The authors declare that there is no conflict of interest.

References

1 

WA Craig S Gudmundsson V. Lorian Postantibiotic effectAntibiotics in laboratory medicineWilliams & WilkinsBaltimore1996296329

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WA Craig Post-antibiotic effects in experimental infection models: relationship to in-vitro phenomena and to treatment of infections in manJ Antimicrob Chemother199331suppl D1495810.1093/jac/31.suppl_d.149

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WA Craig S Gudmundsson V Lorian The postantibiotic effectAntibiotics in Laboratory Medicine3rd edition199940331

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TR Beam DN Gilbert CM Kunin General Guidelines for the Clinical Evaluation of Anti-Infective Drug ProductsClin Infect Dis199215Supplement_1S5S3210.1093/clind/15.supplement_1.s5

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JW Bigger Treatment of staphylococcal infections with penicillin by intermittent sterilisationLancet1944244632049750010.1016/s0140-6736(00)74210-3

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GL Barrow RKA Feltham Cowan and Steel's manual for the identification of medical bacteriaCambridge University PressCambridge2003

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AA Miles SS Misra JO Irwin The estimation of the bactericidal power of the bloodEpidemiol Infect19383867324910.1017/s002217240001158x

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FM MacKenzie IM Gould The post-antibiotic effectJ Antimicrob Chemother19933245193710.1093/jac/32.4.519

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NX Chin HC Neu Post-antibiotic suppressive effect of ciprofloxacin against gram-positive and gram-negative bacteriaAm J Med1987274A5862

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L Licata CE Smith RM Goldschmidt JF Barrett M Frosco Comparison of the postantibiotic and postantibiotic sub-MIC effects of levofloxacin and ciprofloxacin on Staphylococcus aureus and Streptococcus pneumoniae.Antimicrob Agents Chemother1997415950510.1128/aac.41.5.950

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JM Schierholz J Beuth G Pulverer Killing effects of antibiotics and two-fold antimicrobial combinations on proliferating and non growing staphylococciZentralblatt für Bakteriol199828845273910.1016/s0934-8840(98)80072-8

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V Majtán L Majtánová Postantibiotic effects and postantibiotic sub-MIC effects of ciprofloxacin, pefloxacin and amikacin on the biological properties ofSalmonella strainsFolia Microbiol19974243273210.1007/bf02816944

13 

JMR Martínez R Santiso J Machuca G Bou Á Pascual JL Fernández Assessment of Chromosomal DNA Fragmentation by Quinolones in an Isogenic Collection of Escherichia coli with Defined Resistance MechanismsMicrobial Drug Resist2016225354910.1089/mdr.2015.0298



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Article type

Original Article


Article page

262-264


Authors Details

Abdelrahman M A Saeed


Article History

Received : 24-10-2020

Accepted : 06-11-2020


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