The role of combination of Meropenem with gentamicin in reducing emergence of antibiotic resistance in some highly resistant staphylococcus species in vitro
Authors: Abd Abdulkareem Hameed 
Published: August 2023

Background: Staphylococci are considered clinically one of the most important pathogens causes pneumonia, meningitis, boils, arthritis and osteomyelitis. As well as keratitis and urinary tract infections. Emergence of resistant strains of Staphylococcus for a wide range of antibiotics considered a major dilemma leading to failure of infections treatment. The famous example is Methicillin Resistant Staph aureus (MRSA). Meropenem is one of the carbapenem antimicrobials acts through inhibiting bacterial cell wall synthesis. Gentamicin is one of aminoglycosides group act through inhibiting of direct primarily bacterial protein synthesis. Aim of this study is to evaluate the effect of meropenem alone and in combination with gentamicin on Staphylococci to determine the efficacy of combination of meropenem and gentamicin on prevention the emergence of resistant Staphylococcus. Materials and methods: fifty Samples collected by  culturing urine samples and scraping  infected cornea of patients attained to Al-Kadhimia and Ibn-Al Haitham eye hospitals for period between April to September/2011,identification of staphylococcus depend on morphological tests using gram's stain smears and colonies morphology   , biochemical tests including   and API staph system. The disc diffusion method was used to test the antibiotic sensitivity of the isolates. Broth dilution method was used to determine the minimum inhibitory concentration (MIC) of Meropenem, Gentamicin, and their combinations. Fractional inhibitory concentration (FIC) values were used to assess the synergism between meropenem and gentamicin. Two isolates (Staph. aureus and Staph. epidermidis) was cultivate in 1/4 MIC of meropenem and gentamicin for 18 hours and repeating this step for consequent seven times. After the 7th passage the new MIC value of Meropenem and gentamicin for these two isolates were measured.  Results: Staphylococcus species was 13 of all isolates (26 %). Percentage of resistance for the tested antibiotics were  Bacitracin 15 % ; : Trimethoprim 30.7 ; Kanamycin 61% ; Vancomycin 30.7 ;  Cephalexine 46%  ; Chloromphenicol 23 % ;  Streptomycin 23 % ;  Rifampicin 7.7 % ;  Ciprofloxacin 23 % ; Gentamicin 46 % ;  Meropenem 15.3 %;    Oxacillin 7.7 %.  MIC values for meropenem were 0.5- 4 µg/ml for sensitive isolates (84.7 %) and  9-12 µg/ml for resistant isolates (15.3 %), while for gentamicin 2-4 µg/ml for sensitive isolates (54 %)  and  24-50 µg/ml for resistant isolates  ( 46 % ). FIC values for three isolates were 2 ( no effect for combination) while the values were 0.5 (synergistic effect ) for 11 isolates. Passing Staphylococci in 1/4 MIC for seven days increase the MIC values for meropenem from 2 µg/ml to >250 µg/ml in Staph aureus and from 4 µg/ml to >250 µg/ml   in Staph epidermidis, and for gentamicin from 6 µg/ml to >250 µg/ml   in Staph aureus and from 4 µg/ml to >250 µg/ml in Staph epidermidis. The results of this study revealed the synergistic activity of combinations of meropenem and gentamicin on Staph aureus and Staph epidermidis, even with sub-inhibitory concentration (1/4 + 1/4; 1/2 + 1/2). Such combinations will reduce prevalence of resistance and improve therapeutic outcomes and may prevent the development of resistance.