Antibiotic susceptibility profile and synergistic effect of non-steroidal anti-inflammatory drugs on antibacterial activity of resistant antibiotics (Oxytetracycline and Gentamicin) against methicillin resistant Staphylococcus aureus (MRSA)

Microb Pathog. 2019 Dec:137:103755. doi: 10.1016/j.micpath.2019.103755. Epub 2019 Sep 19.

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) may exhibit antibacterial activity and have synergistic effects with antibiotics. One way to re-sensitize MRSA to resistant antibiotics is by combining with approved non-antibiotics. The study was intended to explore susceptibility of MRSA to various antibiotics and non-antibiotics (NSAIDs) by micro dilution broth method. MRSA isolates were confirmed by PCR (mecA gene) and in-vitro antibiotic susceptibility was determined by disc diffusion tests. Combinations of NSAIDs with resistant antibiotics were also evaluated in in-vivo trial in mice. In-vitro antibiotic susceptibility profile presented 100% resistance to Cefoxitin, 37.5% to Gentamicin and Amikacin, 25% to Oxytetracycline, 12.5% to Tylosin, Fusidic acid and Vancomycin, while Ciprofloxacin, Levofloxacin, Moxifloxacin, Trimethoprim + Sulfamethoxazole and Linezolid were found sensitive. Synergistic effect was observed when resistant antibiotics (Oxytetracycline/Gentamicin) were combined with sensitive antibiotics (Ciprofloxacin/Linezolid). Combination of Non-antibiotics (NSAIDs) with resistant antibiotics revealed that Meloxicam showed partial synergism with both Oxytetracycline and Gentamicin, while Flunixin Meglumine presented synergistic effect with Oxytetracycline and partial synergism with Gentamicin. Diclofenac Sodium revealed additive effect with Oxytetracycline while in case of Gentamicin indifferent effect was observed. In-vivo results showed that combinations of Oxytetracycline with Meloxicam/Flunixin Meglumine and Gentamicin with Meloxicam/Flunixin Meglumine were effective. The study concluded that the resistance against milk borne zoonotic MRSA infections can be successfully addressed by combining resistant antibiotics with NSAIDs. Flunixin Meglumine can be used in combination with oxytetracycline against MRSA infection.

Keywords: Dairy goats; Drugs susceptibility profile; Methicillin resistant Staphylococcus aureus; NSAIDs.

MeSH terms

  • Amikacin
  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Bacterial Proteins / genetics
  • Drug Combinations
  • Drug Synergism
  • Female
  • Gentamicins / pharmacology*
  • Goats
  • Mastitis / microbiology
  • Mastitis / veterinary
  • Methicillin-Resistant Staphylococcus aureus / drug effects*
  • Methicillin-Resistant Staphylococcus aureus / genetics
  • Methicillin-Resistant Staphylococcus aureus / isolation & purification
  • Mice
  • Mice, Inbred BALB C
  • Microbial Sensitivity Tests
  • Milk / microbiology
  • Oxytetracycline / pharmacology*
  • Pakistan
  • Penicillin-Binding Proteins / genetics
  • Prevalence
  • Staphylococcal Infections / drug therapy
  • Staphylococcal Infections / veterinary*

Substances

  • Anti-Bacterial Agents
  • Anti-Inflammatory Agents, Non-Steroidal
  • Bacterial Proteins
  • Drug Combinations
  • Gentamicins
  • Penicillin-Binding Proteins
  • mecA protein, Staphylococcus aureus
  • Amikacin
  • Oxytetracycline