Effect of Sodium Diclofenac on Serum and Tissue Concentration of Amoxicillin and on Staphylococcal Infection

Groppo, Francisco Carlos; Simões, Roberta Pessoa; Ramacciato, Juliana Cama; Rehder, Vera Lúcia Garcia; Andrade, Eduardo Dias de; Mattos-Filho, Thales Rocha de

doi:10.1248/bpb.27.52

Cited by 15 publications

(24 citation statements)

References 25 publications

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“…It is well stablished that bacteria growing in tissues surrounded by immune cells show slow reproduction, which decreases the penicillin activity. 17 …”

Section: Discussionmentioning

confidence: 99%

Antimicrobial Activity of Two Garlic Species (Allium Sativum and A. Tuberosum) Against Staphylococci Infection. In Vivo Study in Rats

Pc¹,

et al. 2017

Adv Pharm Bull

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Purpose: This study observed the effect of garlic extracts and amoxicillin against an induced staphylococcal infection model. MIC and MBC were also obtained for aqueous extracts of Allium sativum (Asa) and Allium tuberosum (Atu) against Staphylococcus aureus penicillin-sensitive (PSSA - ATCC 25923) and MRSA (ATCC 33592). Methods: Granulation tissues were induced in the back of 205 rats. After 14 days, 0.5 mL of 108 CFU/mL of PSSA or MRSA were injected inside tissues. After 24h, animals were divided: G1 (Control) – 0.5 mL of NaCl 0.9%; G2 – Asa 100 mg/kg or 400mg/kg; G3 – Atu 100 mg/kg or 400 mg/kg; G4 – amoxicillin suspension 50 mg/kg, considering PSSA infection; and G5 (Control) - 0.5 mL of NaCl 0.9%; G6 – Asa 400mg/kg; G7 – amoxicillin 50 mg/kg; and G8 - Asa 400 mg/kg + amoxicillin 50 mg/kg for MRSA. All treatments were administered P.O. every 6h. Animals were killed at 0, 6, 12 and 24h. Samples were spread on salt-mannitol agar. Colonies were counted after 18 h at 37 °C. Atu was not able to inhibit or kill PSSA and MRSA. Considering Asa, MIC and MBC against PSSA were 2 mg/mL and 4 mg/mL, respectively; and 16 mg/mL and 64 mg/mL against MRSA. Results: No effect was observed in vivo for control, Asa 100 mg/kg and Atu 100 mg/kg, while amoxicillin, Atu 400 mg/kg and Asa 400 mg/kg decreased PSSA counts in all-time points. No effect of any group against MRSA was observed at any time. Conclusion: Thus, A. sativum and A. tuberosum were able to reduce PSSA infection, but not MRSA infection.

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“…It is well stablished that bacteria growing in tissues surrounded by immune cells show slow reproduction, which decreases the penicillin activity. 17 …”

Section: Discussionmentioning

confidence: 99%

Antimicrobial Activity of Two Garlic Species (Allium Sativum and A. Tuberosum) Against Staphylococci Infection. In Vivo Study in Rats

Pc¹,

et al. 2017

Adv Pharm Bull

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“…Diclofenac has been shown to significantly reduce S. aureus counts from rat granulomatous tissue in the absence of antibiotic [16]. This observation might result from host-specific effects (i.e.…”

Section: Discussionmentioning

confidence: 99%

“…The NSAID diclofenac is antibacterial in vitro , and administration to mice or rats infected with Listeria monocytogenes, Salmonella typhimurium, Mycobacterium tuberculosis or S. aureus has been reported to significantly reduce bacterial pathogen cell counts in blood and in organ homogenates [16-18]. Growth of E. coli with inhibitory concentrations (2 × MIC or 100 μg/ml) of diclofenac was shown to reduce the rate of Ci ( 3 H) deoxythymidine incorporation into DNA, indicating that diclofenac may target DNA biosynthesis [19].…”

Section: Introductionmentioning

confidence: 99%

Alterations in the transcriptome and antibiotic susceptibility of Staphylococcus aureus grown in the presence of diclofenac

Riordan

Dupre

Cantore-Matyi

et al. 2011

Ann Clin Microbiol Antimicrob

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BackgroundDiclofenac is a non-steroidal anti-inflammatory drug (NSAID) which has been shown to increase the susceptibility of various bacteria to antimicrobials and demonstrated to have broad antimicrobial activity. This study describes transcriptome alterations in S. aureus strain COL grown with diclofenac and characterizes the effects of this NSAID on antibiotic susceptibility in laboratory, clinical and diclofenac reduced-susceptibility (DcRS) S. aureus strains.MethodsTranscriptional alterations in response to growth with diclofenac were measured using S. aureus gene expression microarrays and quantitative real-time PCR. Antimicrobial susceptibility was determined by agar diffusion MICs and gradient plate analysis. Ciprofloxacin accumulation was measured by fluorescence spectrophotometry.ResultsGrowth of S. aureus strain COL with 80 μg/ml (0.2 × MIC) of diclofenac resulted in the significant alteration by ≥2-fold of 458 genes. These represented genes encoding proteins for transport and binding, protein and DNA synthesis, and the cell envelope. Notable alterations included the strong down-regulation of antimicrobial efflux pumps including mepRAB and a putative emrAB/qacA-family pump. Diclofenac up-regulated sigB (σB), encoding an alternative sigma factor which has been shown to be important for antimicrobial resistance. Staphylococcus aureus microarray metadatabase (SAMMD) analysis further revealed that 46% of genes differentially-expressed with diclofenac are also σB-regulated. Diclofenac altered S. aureus susceptibility to multiple antibiotics in a strain-dependent manner. Susceptibility increased for ciprofloxacin, ofloxacin and norfloxacin, decreased for oxacillin and vancomycin, and did not change for tetracycline or chloramphenicol. Mutation to DcRS did not affect susceptibility to the above antibiotics. Reduced ciprofloxacin MICs with diclofenac in strain BB255, were not associated with increased drug accumulation.ConclusionsThe results of this study suggest that diclofenac influences antibiotic susceptibility in S. aureus, in part, by altering the expression of regulatory and structural genes associated with cell wall biosynthesis/turnover and transport.

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“…Groppo et al [14] demonstrated that sodium diclofenac could significantly reduce amoxicillin blood levels in rats, which was probably not caused by interference with metabolism or renal excretion, since amoxicillin and diclofenac have different pharmacokinetics (plasma protein binding, excretion and metabolism).…”

Section: Discussionmentioning

confidence: 99%

“…Co-administration of amoxicillin with NSAIDs is common in dentistry and medicine [13]. A previous study in rats showed that both amoxicillin tissue and serum concentrations were significantly reduced by sodium diclofenac [14].…”

Section: Introductionmentioning

confidence: 99%

Effect of sodium diclofenac on the bioavailability of amoxicillin

Bergamaschi¹,

Motta²,

Franco³

et al. 2006

International Journal of Antimicrobial Agents

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Effect of Sodium Diclofenac on Serum and Tissue Concentration of Amoxicillin and on Staphylococcal Infection

Cited by 15 publications

References 25 publications

Antimicrobial Activity of Two Garlic Species (Allium Sativum and A. Tuberosum) Against Staphylococci Infection. In Vivo Study in Rats

Antimicrobial Activity of Two Garlic Species (Allium Sativum and A. Tuberosum) Against Staphylococci Infection. In Vivo Study in Rats

Alterations in the transcriptome and antibiotic susceptibility of Staphylococcus aureus grown in the presence of diclofenac

Effect of sodium diclofenac on the bioavailability of amoxicillin

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