In vitro synergism of β-lactams with ciprofloxacin and moxifloxacin against genetically distinct multidrug-resistant isolates of Pseudomonas aeruginosa

Kanellakopoulou, Kyriaki; Sarafis, Pavlos; Galani, Irene; Giamarellou, Helen; Giamarellos‐Bourboulis, Evangelos J.

doi:10.1016/j.ijantimicag.2008.02.019

Cited by 17 publications

(8 citation statements)

References 19 publications

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“…As observed in other studies 26,27 , the rate of synergy of antibacterial combinations varies according to isolate and is not strictly associated with susceptibility or resistance to imipenem. Comparison of the two multidrug-resistant P. aeruginosa isolates revealed more frequent and signifi cant drug MIC reductions for the 46R isolate than for the 72R isolate.…”

Section: Discussionsupporting

confidence: 52%

In vitro activity of antimicrobial combinations against multidrug-resistant Pseudomonas aeruginosa

Santos

Nascimento

Vitali

et al. 2013

Rev. Soc. Bras. Med. Trop.

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Introduction: Pseudomonas aeruginosa isolates related to nosocomial infections are often resistant to multiple antibacterial agents. In this study, antimicrobial combinations were evaluated to detect in vitro synergy against clinical isolates of P. aeruginosa. Methods: Four clinical P. aeruginosa isolates were selected at random among other isolates from inpatients treated at the public University hospital in Ribeirão Preto, SP, Brazil. Two isolates were susceptible to imipenem (IPM-S) and several other antimicrobials, while the other two isolates were imipenem and multidrug resistant (IPM-R). The checkerboard method was used to assess the interactions between antimicrobials. Results: Combinations of imipenem or other anti-Pseudomonas drugs with complementary antibiotics, such as aminoglycosides, fosfomycin and rifampin, reached synergy rates of 20.8%, 50%, 62.5% and 50% for the two IPM-S and two IPM-R Pseudomonas isolates, respectively. Imipenem, piperacillin-tazobactam and ceftazidime yielded a greater synergy rate than cefepime or ciprofl oxacin. Synergist combinations were more commonly observed when the complementary drug was tobramycin (65%) or fosfomycin (57%). Conclusions: Some antibacterial combinations led to signifi cant reductions of the minimum inhibitory concentrations of both drugs, suggesting that they could be clinically applied to control infections caused by multidrug-resistant P. aeruginosa.

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Section: Discussionsupporting

confidence: 52%

In vitro activity of antimicrobial combinations against multidrug-resistant Pseudomonas aeruginosa

Santos

Nascimento

Vitali

et al. 2013

Rev. Soc. Bras. Med. Trop.

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“…Some studies investigated this combination for the treatment of P. aeruginosa infection. However, comparisons of these results are hampered because of methodological differences, with differences in the percentages of synergism of 74.5% in the United States (14), 22.0% and 61.0% in Turkey (12), and 8.0% in Greece (8). Also, no synergism of the MCC was observed with American isolates (29) and Italian isolates (30).…”

Section: Discussionmentioning

confidence: 99%

Structural Changes and Differentially Expressed Genes in Pseudomonas aeruginosa Exposed to Meropenem-Ciprofloxacin Combination

Siqueira

Cardoso

Caleffi-Ferracioli

et al. 2014

Antimicrob Agents Chemother

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The effect of a meropenem-ciprofloxacin combination (MCC) on the susceptibility of multidrug-resistant (MDR) Pseudomonas aeruginosa (MRPA) clinical isolates was determined using checkerboard and time-kill curve techniques. Structural changes and differential gene expression that resulted from the synergistic action of the MCC against one of the P. aeruginosa isolates (1071-MRPA]) were evaluated using electron microscopy and representational difference analysis (RDA), respectively. The differentially expressed, SOS response-associated, and resistance-associated genes in 1071-MRPA exposed to meropenem, ciprofloxacin, and the MCC were monitored by quantitative PCR. The MCC was synergistic against 25% and 40.6% of MDR P. aeruginosa isolates as shown by the checkerboard and time-kill curves, respectively. The morphological and structural changes that resulted from the synergistic action of the MCC against 1071-MRPA were a summation of the effects observed with each antimicrobial alone. One exception included outer membrane vesicles, which were seen in a greater amount upon ciprofloxacin exposure but were significantly inhibited upon MCC exposure. Cell wall-and DNA repair-associated genes were differentially expressed in 1071-MRPA exposed to meropenem, ciprofloxacin, and the MCC. However, some of the RDA-detected, resistance-associated, and SOS response-associated genes were expressed at significantly lower levels in 1071-MRPA exposed to the MCC. The MCC may be an alternative for the treatment of MDR P. aeruginosa. The effect of this antimicrobial combination may be not only the result of a summation of the effects of meropenem and ciprofloxacin but also a result of differential action that likely inhibits protective mechanisms in the bacteria. Pseudomonas aeruginosa is a highly successful opportunistic pathogen that displays intrinsic multidrug resistance and has a great ability to acquire further resistance mechanisms (1, 2). Limited classes of antibiotics can be used for the treatment of P. aeruginosa infection (3). The emergence of multidrug-resistant (MDR) P. aeruginosa (MRPA) has prompted the search for new agents or alternative therapeutics (1, 4, 5), including antimicrobial combinations (6-9).Synergistic interactions between drugs have been investigated to improve therapeutic results, decrease the potential toxicity of antimicrobial agents, and prevent the emergence of bacterial resistance (6, 10, 11). Several studies have evaluated the effects of a meropenem-ciprofloxacin combination (MCC) in P. aeruginosa (12-14), including MDR isolates (8, 15). Despite some differences in the results, likely attributable to variations in techniques and bacterial isolates, the MCC represents a promising antipseudomonal therapeutic option (12)(13)(14). Although ␤-lactams and fluoroquinolones represent classic antimicrobials with previously known mechanisms of action, the molecular basis of synergism between these classes of drugs has not yet been elucidated.Thus, because of high rates of resistance observed in Brazilian P. ae...

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“…It is also reported that polymyxin B can be used in combination with other antimicrobials to treat multidrug resistant (MDR) gram-negative respiratory tract infections caused by several clinical strains of P. aeruginosa 6. Also, fluoroquinolones in combination with potent anti-pseudomonal β-lactam agents are reported to prevent the development of resistance in P. aeruginosa 7-8. Earlier, Marie et al .…”

Section: Introductionmentioning

confidence: 99%

Activity and interactions of antibiotic and phytochemical combinations against Pseudomonas aeruginosa in vitro

Jayaraman¹,

Sakharkar²,

Lim³

et al. 2010

Int. J. Biol. Sci.

184

113

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In this study the in vitro activities of seven antibiotics (ciprofloxacin, ceftazidime, tetracycline, trimethoprim, sulfamethoxazole, polymyxin B and piperacillin) and six phytochemicals (protocatechuic acid, gallic acid, ellagic acid, rutin, berberine and myricetin) against five P. aeruginosa isolates, alone and in combination are evaluated. All the phytochemicals under investigation demonstrate potential inhibitory activity against P. aeruginosa. The combinations of sulfamethoxazole plus protocatechuic acid, sulfamethoxazole plus ellagic acid, sulfamethoxazole plus gallic acid and tetracycline plus gallic acid show synergistic mode of interaction. However, the combinations of sulfamethoxazole plus myricetin shows synergism for three strains (PA01, DB5218 and DR3062). The synergistic combinations are further evaluated for their bactericidal activity against P. aeruginosa ATCC strain using time-kill method. Sub-inhibitory dose responses of antibiotics and phytochemicals individually and in combination are presented along with their interaction network to suggest on the mechanism of action and potential targets for the phytochemicals under investigation. The identified synergistic combinations can be of potent therapeutic value against P. aeruginosa infections. These findings have potential implications in delaying the development of resistance as the antibacterial effect is achieved with lower concentrations of both drugs (antibiotics and phytochemicals).

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In vitro synergism of β-lactams with ciprofloxacin and moxifloxacin against genetically distinct multidrug-resistant isolates of Pseudomonas aeruginosa

Cited by 17 publications

References 19 publications

In vitro activity of antimicrobial combinations against multidrug-resistant Pseudomonas aeruginosa

In vitro activity of antimicrobial combinations against multidrug-resistant Pseudomonas aeruginosa

Structural Changes and Differentially Expressed Genes in Pseudomonas aeruginosa Exposed to Meropenem-Ciprofloxacin Combination

Activity and interactions of antibiotic and phytochemical combinations against Pseudomonas aeruginosa in vitro

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