1887

Abstract

is one of the challenging drug-resistant organisms that can endanger patients' lives if not treated properly.

This study was designed to investigate the activity of three synergistic antimicrobial combinations against extensive drug-resistant isolates; ampicillin/sulbactam plus amikacin, ampicillin/sulbactam plus ciprofloxacin, and meropenem plus amikacin.

Minimum inhibitory concentrations of 100 XDR- isolates were determined using the Vitek2 system. The broth micro-dilution method was performed to determine tigecycline MIC. Checkerboard assay was used to evaluate activity of the three antibiotic combinations.

MIC results by the Vitek 2C system revealed that all isolates were resistant to all tested antibiotics except for colistin against which no resistance was reported. As for tigecycline, all isolates were susceptible. Regarding MIC results of each antibiotic, all isolates were resistant to meropenem and ciprofloxacin. While 95 % of isolates were resistant to both ampicillin/sulbactam and amikacin. The activities of antibiotic combinations by checkerboard assay were as follows: ampicillin/sulbactam plus amikacin was synergic in 52 %, additive 40 % and indifferent in 8 % of isolates, ampicillin/sulbactam plus ciprofloxacin was synergic in 40 %, additive 46 % and indifferent in 14 % of isolates, meropenem/amikacin combination was synergic in 22 %, additive in 49 % of isolates and indifferent in 29 % of isolates. No antagonistic activity was detected against any of the tested antibiotic combinations.

Ampicillin/sulbactam plus amikacin showed the highest synergistic activity followed by ampicillin/sulbactam plus ciprofloxacin. This reflects the value of adding aminoglycosides to either of a β-lactam or quinolone. The tested antibiotic combinations are promising treatment options for XDR-.

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2023-02-09
2024-10-10
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References

  1. Almasaudi SB. Acinetobacter spp. as nosocomial pathogens: epidemiology and resistance features. Saudi J Biol Sci 2018; 25:586–596 [View Article] [PubMed]
    [Google Scholar]
  2. Izadpanah M, Khalili H. Antibiotic regimens for treatment of infections due to multidrug-resistant Gram-negative pathogens: an evidence-based literature review. J Res Pharm Pract 2015; 4:105–114 [View Article] [PubMed]
    [Google Scholar]
  3. Nowak J, Zander E, Stefanik D, Higgins PG, Roca I et al. High incidence of pandrug-resistant Acinetobacter baumannii isolates collected from patients with ventilator-associated pneumonia in Greece, Italy and Spain as part of the MagicBullet clinical trial. J Antimicrob Chemother 2017; 72:3277–3282 [View Article] [PubMed]
    [Google Scholar]
  4. Reza H. The frequency of multidrug-resistance and extensively drug resistant Acinetobacter baumannii in west of Iran. J Clin Microbiol Infect Dis 2018; 1:4–8
    [Google Scholar]
  5. Hasanin A, Eladawy A, Mohamed H, Salah Y, Lotfy A et al. Prevalence of extensively drug-resistant gram negative bacilli in surgical intensive care in Egypt. Pan Afr Med J 2014; 19:177 [View Article] [PubMed]
    [Google Scholar]
  6. Nageeb W, Kamel M, Zakaria S, Metwally L. Phenotypic characterization of Acinetobacter baumannii isolates from intensive care units at a tertiary-care hospital in Egypt. East Mediterr Health J 2014; 20:203–211 [PubMed]
    [Google Scholar]
  7. Poulikakos P, Tansarli GS, Falagas ME. Combination antibiotic treatment versus monotherapy for multidrug-resistant, extensively drug-resistant, and pandrug-resistant Acinetobacter infections: a systematic review. Eur J Clin Microbiol Infect Dis 2014; 33:1675–1685 [View Article] [PubMed]
    [Google Scholar]
  8. Zhi-Wen Y, Yan-Li Z, Man Y, Wei-Jun F. Clinical treatment of pandrug-resistant bacterial infection consulted by clinical pharmacist. Saudi Pharm J 2015; 23:377–380 [View Article] [PubMed]
    [Google Scholar]
  9. Tängdén T. Combination antibiotic therapy for multidrug-resistant gram-negative bacteria. Ups J Med Sci 2014; 119:149–153 [View Article] [PubMed]
    [Google Scholar]
  10. Taneja N, Kaur H. Insights into newer antimicrobial agents against gram-negative bacteria. Microbiol Insights 2016; 9:9–19 [View Article] [PubMed]
    [Google Scholar]
  11. Kumar A, Safdar N, Kethireddy S, Chateau D. A survival benefit of combination antibiotic therapy for serious infections associated with sepsis and septic shock is contingent only on the risk of death: a meta-analytic/meta-regression study. Crit Care Med 2010; 38:1651–1664 [View Article] [PubMed]
    [Google Scholar]
  12. Tamma PD, Cosgrove SE, Maragakis LL. Combination therapy for treatment of infections with gram-negative bacteria. Clin Microbiol Rev 2012; 25:450–470 [View Article] [PubMed]
    [Google Scholar]
  13. Paul M, Lador A, Grozinsky-Glasberg S, Leibovici L. Beta lactam antibiotic monotherapy versus beta lactam-aminoglycoside antibiotic combination therapy for sepsis. Cochrane Database Syst Rev 2014; 2014:CD003344 [View Article] [PubMed]
    [Google Scholar]
  14. Johns Hopkins Treatment guidelines for adult inpatients, Organism specific guidelines: Multi-drug resistant gram-negative rods. In Johns Hopkins Medicine 2015 pp 28–29
    [Google Scholar]
  15. Magiorakos A-P, Srinivasan A, Carey RB, Carmeli Y, Falagas ME et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect 2012; 18:268–281 [View Article] [PubMed]
    [Google Scholar]
  16. Clinical and Laboratory Standards Institute (CLSI) Performance standards for antimicrobial susceptibility testing; twenty-eighth edition (M100) Wayne, PA: Clinical and Laboratory Standards Institute; 2018
    [Google Scholar]
  17. EUCAST Breakpoint tables for interpretation of MICs and zone diameters. Version 5.0, valid from 2015-01-01 2015 http://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/Breakpoint_tables/v_5.0_Breakpoint_Table_01.pdf
    [Google Scholar]
  18. Pillai SK, Moellering RC, Eliopoulos GM. Antimicrobial combinations. In Lorian V. eds Antibiotics in Laboratory Medicine Philadelphia, Pa, USA: Lippincott Williams and Wilkins; 2005 pp 365–440
    [Google Scholar]
  19. Clinical and Laboratory Standards Institute (CLSI) Performance standards for antimicrobial susceptibility testing, Twenty-fifth informational supplement M100-S25. Wayne, PA, USA: Clinical and Laboratory Standards Institute; 2015
    [Google Scholar]
  20. Clinical and Laboratory Standards Institute (CLSI) Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically, Tenth Edition M07-A10. Wayne, PA, USA: Clinical and Laboratory Standards Institute; 2015
    [Google Scholar]
  21. Nhung PH, Miyoshi-Akiyama T, Phuong DM, Shimada K, Anh NQ et al. Evaluation of the Etest method for detecting colistin susceptibility of multidrug-resistant gram-negative isolates in Vietnam. J Infect Chemother 2015; 21:617–619 [View Article] [PubMed]
    [Google Scholar]
  22. Madadi-Goli N, Moniri R, Bagheri-Josheghani S, Dasteh-Goli N. Sensitivity of levofloxacin in combination with ampicillin-sulbactam and tigecycline against multidrug-resistant Acinetobacter baumannii. Iran J Microbiol 2017; 9:19–25 [PubMed]
    [Google Scholar]
  23. Drago L, De Vecchi E, Nicola L, Colombo A, Guerra A et al. Activity of levofloxacin and ciprofloxacin in combination with cefepime, ceftazidime, imipenem, piperacillin-tazobactam and amikacin against different Pseudomonas aeruginosa phenotypes and Acinetobacter spp. Chemotherapy 2004; 50:202–210 [View Article] [PubMed]
    [Google Scholar]
  24. Leber AL. Synergism Testing: broth microdilution checkerboard and broth macrodilution methods. In Clinical Microbiology Procedures Handbook Washington, DC: ASM press; 2016 p 5 https://doi.org/10.1128/9781555818814.ch5.16
    [Google Scholar]
  25. Horrevorts AM, de Ridder CM, Poot MC, de Jonge MJ, Degener JE et al. Chequerboard titrations: the influence of the composition of serial dilutions of antibiotics on the fractional inhibitory concentration index and fractional bactericidal concentration index. J Antimicrob Chemother 1987; 19:119–125 [View Article] [PubMed]
    [Google Scholar]
  26. Ayukekbong JA, Ntemgwa M, Atabe AN. The threat of antimicrobial resistance in developing countries: causes and control strategies. Antimicrob Resist Infect Control 2017; 6:47 [View Article] [PubMed]
    [Google Scholar]
  27. Yavaş S, Yetkin MA, Kayaaslan B, Baştuğ A, Aslaner H et al. Investigating the in vitro synergistic activities of several antibiotic combinationsagainst carbapenem-resistant Acinetobacter baumannii isolates. Turk J Med Sci 2016; 46:892–896 [View Article] [PubMed]
    [Google Scholar]
  28. Livermore DM, Hill RLR, Thomson H, Charlett A, Turton JF et al. Antimicrobial treatment and clinical outcome for infections with carbapenem- and multiply-resistant Acinetobacter baumannii around London. Int J Antimicrob Agents 2010; 35:19–24 [View Article] [PubMed]
    [Google Scholar]
  29. Temocin F, Erdinc FS, Tulek N, Demirelli M, Ertem G et al. Synergistic effects of sulbactam in multi-drug-resistant Acinetobacter baumannii. Braz J Microbiol 2015; 46:1119–1124 [View Article] [PubMed]
    [Google Scholar]
  30. Teo J, Lim T-P, Hsu L-Y, Tan T-Y, Sasikala S et al. Extensively drug-resistant Acinetobacter baumannii in a Thai hospital: a molecular epidemiologic analysis and identification of bactericidal Polymyxin B-based combinations. Antimicrob Resist Infect Control 2015; 4:2 [View Article] [PubMed]
    [Google Scholar]
  31. Hsueh P-R, Teng L-J, Chen C-Y, Chen W-H, Yu C-J et al. Pandrug-resistant Acinetobacter baumannii causing nosocomial infections in a university hospital, Taiwan. Emerg Infect Dis 2002; 8:827–832 [View Article] [PubMed]
    [Google Scholar]
  32. Swenson JM, Killgore GE, Tenover FC. Antimicrobial susceptibility testing of Acinetobacter spp. by NCCLS broth microdilution and disk diffusion methods. J Clin Microbiol 2004; 42:5102–5108 [View Article] [PubMed]
    [Google Scholar]
  33. Hawley JS, Murray CK, Griffith ME, McElmeel ML, Fulcher LC et al. Susceptibility of Acinetobacter strains isolated from deployed U.S. military personnel. Antimicrob Agents Chemother 2007; 51:376–378 [View Article] [PubMed]
    [Google Scholar]
  34. Huang YS, Wang JT, Sheng WH, Chuang YC, Chang SC. Comparative in vitro activity of sitafloxacin against bacteremic isolates of carbapenem resistant Acinetobacter baumannii complex. J Microbiol Immunol Infect 2015; 48:545–551 [View Article] [PubMed]
    [Google Scholar]
  35. Tas T, Kocoglu E, Mengeloglu Z, Bucak O, Karabörk S. Investigation of in-vitro susceptibility of multidrug-resistant Acinetobacter baumannii strains isolated from clinical specimens to tigecycline. Bosn J Basic Med Sci 2013; 13:266–270 [View Article] [PubMed]
    [Google Scholar]
  36. Dizbay M, Tozlu DK, Cirak MY, Isik Y, Ozdemir K et al. In vitro synergistic activity of tigecycline and colistin against XDR-Acinetobacter baumannii. J Antibiot (Tokyo) 2010; 63:51–53 [View Article] [PubMed]
    [Google Scholar]
  37. Yadav R, Landersdorfer CB, Nation RL, Boyce JD, Bulitta JB. Novel approach to optimize synergistic carbapenem-aminoglycoside combinations against carbapenem-resistant Acinetobacter baumannii. Antimicrob Agents Chemother 2015; 59:2286–2298 [View Article] [PubMed]
    [Google Scholar]
  38. Yadav R, Bulitta JB, Nation RL, Landersdorfer CB. Optimization of synergistic combination regimens against carbapenem- and aminoglycoside-resistant clinical Pseudomonas aeruginosa isolates via mechanism-based pharmacokinetic/pharmacodynamic modeling. Antimicrob Agents Chemother 2017; 61:e01011-16 [View Article] [PubMed]
    [Google Scholar]
  39. Hsu L-Y, Apisarnthanarak A, Khan E, Suwantarat N, Ghafur A et al. Carbapenem-resistant Acinetobacter baumannii and Enterobacteriaceae in South and Southeast Asia. Clin Microbiol Rev 2017; 30:1–22 [View Article] [PubMed]
    [Google Scholar]
  40. Abdallah M, Alsaleh H, Baradwan A, Alfawares R, Alobaid A et al. Intraventricular tigecycline as a last resort therapy in a patient with difficult-to-treat healthcare-associated Acinetobacter baumannii ventriculitis: a case report. SN Compr Clin Med 2020; 2:1683–1687 [View Article] [PubMed]
    [Google Scholar]
  41. Tucker H, Wible M, Gandhi A, Quintana A. Efficacy of intravenous tigecycline in patients with Acinetobacter complex infections: results from 14 Phase III and Phase IV clinical trials. Infect Drug Resist 2017; 10:401–417 [View Article]
    [Google Scholar]
  42. Zhou Y, Chen X, Xu P, Zhu Y, Wang K et al. Clinical experience with tigecycline in the treatment of hospital-acquired pneumonia caused by multidrug resistant Acinetobacter baumannii. BMC Pharmacol Toxicol 2019; 20:19 [View Article]
    [Google Scholar]
  43. Huttner B, Jones M, Rubin MA, Neuhauser MM, Gundlapalli A et al. Drugs of last resort? The use of polymyxins and tigecycline at US Veterans Affairs medical centers, 2005-2010. PLoS One 2012; 7:e36649 [View Article]
    [Google Scholar]
  44. Dixit D, Madduri RP, Sharma R. The role of tigecycline in the treatment of infections in light of the new black box warning. Expert Rev Anti Infect Ther 2014; 12:397–400 [View Article]
    [Google Scholar]
  45. Lv D, Zuo Y, Wang Y, Wang Z, Xu Y. Predictors of occurrence and 30-day mortality for co-infection of carbapenem-resistant Klebsiella pneumoniae and carbapenem-resistant Acinetobacter baumannii. Front Cell Infect Microbiol 2022; 12:919414 [View Article]
    [Google Scholar]
  46. Shi X, Zuo C, Yu L, Lao D, Li X et al. Real-world data of tigecycline-associated drug-induced liver injury among patients in China: a 3-year retrospective study as assessed by the updated RUCAM. Front Pharmacol 2021; 12:761167 [View Article] [PubMed]
    [Google Scholar]
  47. Prasad P, Sun J, Danner RL, Natanson C. Excess deaths associated with tigecycline after approval based on noninferiority trials. Clin Infect Dis 2012; 54:1699–1709 [View Article] [PubMed]
    [Google Scholar]
  48. Chiang M-H, Yang Y-S, Sun J-R, Wang Y-C, Kuo S-C et al. Confronting tigecycline-resistant Acinetobacter baumannii via immunization against conserved resistance determinants. Front Microbiol 2020; 11:536 [View Article] [PubMed]
    [Google Scholar]
  49. Savov E, Chankova D, Vatcheva R, Dinev N. In vitro investigation of the susceptibility of Acinetobacter baumannii strains isolated from clinical specimens to ampicillin/sulbactam alone and in combination with amikacin. Int J Antimicrob Agents 2002; 20:390–392 [View Article] [PubMed]
    [Google Scholar]
  50. Dinc G, Demiraslan H, Elmali F, Ahmed SS, Alp E et al. Antimicrobial efficacy of doripenem and its combinations with sulbactam, amikacin, colistin, tigecycline in experimental sepsis of carbapenem-resistant Acinetobacter baumannii. New Microbiol 2015; 38:67–73 [PubMed]
    [Google Scholar]
  51. Wang FJ, Lyu Y, Liu ZH, Li Y, Cui LQ. In vitro Activity of different antibacterial agents in combination with each other against multidrug-resistant Acinetobacter baumannii. Chin Med J (Engl) 2016; 129:2388–2389 [View Article] [PubMed]
    [Google Scholar]
  52. Singkham-In U, Chatsuwan T. In vitro activities of carbapenems in combination with amikacin, colistin, or fosfomycin against carbapenem-resistant Acinetobacter baumannii clinical isolates. Diagn Microbiol Infect Dis 2018; 91:169–174 [View Article] [PubMed]
    [Google Scholar]
  53. Al-Hasan MN, Wilson JW, Lahr BD, Thomsen KM, Eckel-Passow JE et al. Beta-lactam and fluoroquinolone combination antibiotic therapy for bacteremia caused by gram-negative bacilli. Antimicrob Agents Chemother 2009; 53:1386–1394 [View Article] [PubMed]
    [Google Scholar]
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