Enhanced Antibacterial Activity of Meropenem against Extensively Drug-Resistant Acinetobacter baumannii by Myrtaceae Plant Extracts
Keywords:Acinetobacter baumannii, Combination, Meropenem, Myrtaceae
Acinetobacter baumannii (A. baumannii) has been known as a major cause of nosocomial bacterial infections worldwide. The bacteria are increasingly associated with a broad spectrum of antibiotic resistance, and this has become a widespread concern in a variety of hospitals.Antibiotic development and alternative treatment have become priorities for the treatment of bacterial infections.This study investigated the efficacy of meropenem in combination with five ethanolic extracts of plants in Myrtaceae against extensively drug-resistant (XDR) A. baumannii. The resistant phenotype was previously determined by microdilution method. XDR-A. baumannii strains showed resistance to meropenem with the minimum inhibitory concentration (MIC) in a range of 16 - 128 µg/mL, whereas the MIC value of all extracts, including Calistemon lancealatus, Eucalyptus citridora, Rhodomytus tomentasa, Syzygium cumini, and Xanthortemon chrysanthus, was over 1,000 µg/mL. Interestingly, all extracts potentiated the activity of the antibiotic by reducing the MIC values of the antibiotic. Xanthortemon chrysanthus extract displayed excellent synergism against the bacteria by decreasing the MIC value of the drug greater than 8-fold. In addition, the extract, at concentrations of 31.25, 62.5, 125, 250, 500, and 1,000 µg/mL, obviously increased the inhibitory effect of meropenem (1/4´MIC) against A. baumannii. The percentage of bacterial growth inhibition by combination was 87.9, 88.8, 91.8, 93.6, 99.9, and 100, respectively. The results supported that the extract could improve the activity of ineffective antibiotics against drug-resistant pathogens.Therefore, the findings may serve as therapeutic options for XDR-A. baumannii infections in the future.
C Willyard. The drug-resistant bacteria that pose the greatest health threats. Nature News 2017; 543, 15.
D Wong, TB Nielsen, RA Bonomo, P Pantapalangkoor, B Luna and B Spellberg. Clinical and pathophysiological overview of Acinetobacter infections: A century of challenges. Clin. Microbiol. Rev. 2017; 30, 409-47.
AP Magiorakos, A Srinivasan, R Carey, Y Carmeli, M Falagas, C Giske, S Harbarth, J Hindler, G Kahlmeter and B Olsson-Liljequist. 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, 268-81.
ES Özgür, ES Horasan, K Karaca, G Ersöz, SN Atış and A Kaya. Ventilator-associated pneumonia due to extensive drug-resistant Acinetobacter baumannii: Risk factors, clinical features, and outcomes. Am. J. Infect. Control. 2014; 42, 206-8.
AO Javan, S Shokouhi and Z Sahraei. A review on colistin nephrotoxicity. Eur. J. Clin. Pharmacol. 2015; 71, 801-10.
M Paul, GL Daikos, E Durante-Mangoni, D Yahav, Y Carmeli, YD Benattar, A Skiada, R Andini, N Eliakim-Raz and A Nutman. Colistin alone versus colistin plus meropenem for treatment of severe infections caused by carbapenem-resistant Gram-negative bacteria: An open-label, randomised controlled trial. Lancet Infect. Dis. 2018; 18, 391-400.
E Patridge, P Gareiss, MS Kinch and D Hoyer. An analysis of FDA-approved drugs: Natural products and their derivatives. Drug Discov. Today 2016; 21, 204-7.
MM Cascaes, GMSP Guilhon, EHdA Andrade, MGB Zoghbi and LdS Santos. Constituents and pharmacological activities of Myrcia (Myrtaceae): A review of an aromatic and medicinal group of plants. Int. J. Mol. Sci. 2015; 16, 23881-904.
E Al-Sayed and RN El-Naga. Protective role of ellagitannins from Eucalyptus citriodora against ethanol-induced gastric ulcer in rats: Impact on oxidative stress, inflammation and calcitonin-gene related peptide. Phytomedicine 2015; 22, 5-15.
PE Bitencourt, LM Ferreira, LO Cargnelutti, L Denardi, A Boligon, M Fleck, R Brandão, ML Athayde, L Cruz and RA Zanette. A new biodegradable polymeric nanoparticle formulation containing Syzygium cumini: Phytochemical profile, antioxidant and antifungal activity and in vivo toxicity. Ind. Crop. Prod. 2016; 83, 400-7.
S El-Refai, A Atia and S Mahmoud. Effects of Callistemon citrinus aqueous extract on prepatent and patent infections with Schistosoma mansoni in experimentally infected mice. J. Helminthol. 2018; 93, 1-10.
S Chanda and K Rakholiya. Combination Therapy: Synergism between Natural Plant Extracts and Antibiotics against Infectious Diseases. In: A Mendez-Vilas (Ed.). Science against Microbial Pathogens: Communicating Current Research and Technological Advances. Microbiolology Book Series, Badajos, Spain, 2011, p. 520-9.
CLSI. Performance Standards for Antimicrobial Susceptibility Testing. 27th eds. CLSI Supplement M100, Wayne, PA, 2017.
R Zarrilli, M Giannouli, F Tomasone, M Triassi and A Tsakris. Carbapenem resistance in Acinetobacter baumannii: The molecular epidemic features of an emerging problem in health care facilities. J. Infect. Dev. Ctries 2009; 3, 335-41.
E Righi, AM Peri, PN Harris, AM Wailan, M Liborio, SW Lane and DL Paterson. Global prevalence of carbapenem resistance in neutropenic patients and association with mortality and carbapenem use: Systematic review and meta-analysis. J. Antimicrob. Chemother. 2017; 72, 668-77.
SS Kadri, J Adjemian, YL Lai, AB Spaulding, E Ricotta, DR Prevots, TN Palmore, C Rhee, M Klompas and JP Dekker. Difficult-to-treat resistance in Gram-negative Bacteremia at 173 US Hospitals: Retrospective cohort analysis of prevalence, predictors, and outcome of resistance to all first-line agents. Clin. Infect. Dis. 2018; 67, 1803-14.
X Li, L Wang, XJ Zhang, Y Yang, WT Gong, B Xu, YQ Zhu and W Liu. Evaluation of meropenem regimens suppressing emergence of resistance in Acinetobacter baumannii with human simulated exposure in an in vitro intravenous infusion hollow-fiber infection model. J. Antimicrob. Chemother. 2014; 58, 6773-81.
DE Djeussi, JA Noumedem, BT Ngadjui and V Kuete. Antibacterial and antibiotic-modulation activity of six Cameroonian medicinal plants against Gram-negative multi-drug resistant phenotypes. BMC Compl. Alternative Med. 2016; 16, 124-33.
JA Seukep, LP Sandjo, BT Ngadjui and V Kuete. Antibacterial and antibiotic-resistance modifying activity of the extracts and compounds from Nauclea pobeguinii against Gram-negative multi-drug resistant phenotypes. BMC Compl. Alternat. Med. 2016; 16, 193-201.
M Visutthi. Anti-staphylococcal screening of selected Thai medicinal plants from Nakhon Ratchasima province. Suranaree J. Sci. Technol. 2016; 23, 109-14.
S Chusri, I Villanueva, SP Voravuthikunchai and J Davies. Enhancing antibiotic activity: A strategy to control Acinetobacter infections. J. Antimicrob. Chemother. 2009; 64, 1203-11.
A Duarte, S Ferreira, F Silva and F Domingues. Synergistic activity of coriander oil and conventional antibiotics against Acinetobacter baumannii. Phytomedicine 2012; 19, 236-8.
NL Maia, M de Barros, LL de Oliveira, SA Cardoso, MH dos Santos, FA Pieri, TC Ramalho, EF da Cunha and MA Moreira. Synergism of plant compound with traditional antimicrobials against Streptococcus spp. isolated from bovine mastitis. Front. Microbiol. 2018; 9, 1-10.
AM Somboro, JO Sekyere, DG Amoako, HM Kumalo, R Khan, LA Bester and SY Essack. In vitro potentiation of carbapenems with tannic acid against carbapenemase-producing enterobacteriaceae: Exploring natural products as potential carbapenemase inhibitors. J. Appl. Microbiol. 2019; 126, 452-67.
PB Savage. Multidrug-resistant bacteria: Overcoming antibiotic permeability barriers of Gram-negative bacteria. Ann. Med. 2001; 33, 167-71.
J Vila, S Martí and J Sanchez-Céspedes. Porins, efflux pumps and multidrug resistance in Acinetobacter baumannii. J. Antimicrob. Chemother. 2007; 59, 1210-5.
K Lewis and FM Ausubel. Prospects for plant-derived antibacterials. Nat. Biotechnol. 2006; 24 , 1504-7.
DP Karumathil, MS Nair, J Gaffney, A Kollanoor-Johny and K Venkitanarayanan. Trans-cinnamaldehyde and eugenol increase Acinetobacter baumannii sensitivity to beta-lactam antibiotics. Front. Microbiol. 2018; 9, 1-10.
AR Ball, G Casadei, S Samosorn, JB Bremner, FM Ausubel, TI Moy and K Lewis. Conjugating berberine to a multidrug resistance pump inhibitor creates an effective antimicrobial. ACS Chem. Biol. 2006; 1, 594-600.
JR Lenhard, JB Bulitta, TD Connell, N King-Lyons, CB Landersdorfer, SE Cheah, V Thamlikitkul, BS Shin, G Rao and PN Holden. High-intensity meropenem combinations with polymyxin B: New strategies to overcome carbapenem resistance in Acinetobacter baumannii. J. Antimicrob. Chemother. 2016; 72, 153-65.
D Fernando and A Kumar. Growth phase-dependent expression of RND efflux pump-and outer membrane porin-encoding genes in Acinetobacter baumannii ATCC 19606. ACS Infect. Dis. 2011; 67, 569-72.
Y Zhang, Z Li, X He, F Ding, W Wu, Y Luo, B Fan and H Cao. Overproduction of efflux pumps caused reduced susceptibility to carbapenem under consecutive imipenem-selected stress in Acinetobacter baumannii. Infect. Drug. Resist. 2017; 11, 457-67.
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