NON-FERMENTING GRAM-NEGATIVE BACTERIA - LET'S BE CAUTIOUS
Keywords:
Non-fermenting Gram-negative bacteria, antimicrobial resistance, virulence factorsAbstract
Non-fermenting Gram-negative bacteria are a taxonomically diverse group of aerobic nonspore forming bacteria, the majority of which are able to survive for extended time periods under adverse environmental conditions - dry, cold or warm. They are widely distributed in the environment including soil, water, plants and various other sources. In the hospital environment, they may be isolated from humidifiers, ventilator machines, nebulizers, dialysis fluids, saline solution, disinfectants and medications. They can be part of the transient physiologic flora and can be also found as commensals on the human skin or in the gut. These opportunistic pathogens possess a highly variable level of virulence as a major virulence factor is the ability of biofilm production which facilitates attachment to various surfaces, resistance to phagocytic activity and other host immune factors, protection from antimicrobial activity and enhanced spread across surfaces through bacterial motility. The accurate identification of these bacteria to species level is absolutely important for appropriate patient management. The molecular methods for identification are emerging as alternatives for phenotypic identification methods of these microorganisms and have provided a number of changes in taxonomy, but also contributed important insights into their epidemiology and clinical importance. The non-fermenting Gram-negative bacteria group includes organisms from diverse genera, the most prevalent among which are Pseudomonas, Acinetobacter, Stenotrophomonas, Burkholderia, Alcaligenes, Weeksella, Flavimonas, Achromobacter, Elizabethkingia, etc. Non-fermenting Gram-negative bacteria rarely causes disease in healthy individuals. However, in recent years these bacteria have emerged as important healthcare-associated pathogens. They cause infections in critically ill, immunocompromised or cystic fibrosis patients and are particularly associated with severe urinary tract infections, wound infections, ventilator pneumonia, meningitis, surgical site infections and bloodstream infections significantly increasing morbidity and mortality among the patients. A major issue for the physicians in terms of non-fermenting Gram-negative bacteria infection treatment and control is the emerging challenges of multi-drug resistance, both intrinsic and acquired among them and the rapid emergence of resistance to novel antimicrobial compounds raises concerns about the clinical reliability of these agents which in turn leads to prolonged hospital stay and greater healthcare costs.
References
Amoureux, L., Bador, J., Siebor, E., Taillefumier, N., Fanton, A., & Neuwirth, C. (2013). Epidemiology and resistance of Achromobacter xylosoxidans from cystic fibrosis patients in Dijon, Burgundy: first French data. Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society, 12(2), 170–176. https://doi.org/10.1016/j.jcf.2012.08.005
Bassetti, M., Vena, A., Croxatto, A., Righi, E., & Guery, B. (2018). How to manage Pseudomonas aeruginosa infections. Drugs in context, 7, 212527. https://doi.org/10.7573/dic.212527
Blanco, P., Corona, F., & Martínez, J. L. (2019). Involvement of the RND efflux pump transporter SmeH in the acquisition of resistance to ceftazidime in Stenotrophomonas maltophilia. Scientific reports, 9(1), 4917. https://doi.org/10.1038/s41598-019-41308-9
Chang, Y. T., Lin, C. Y., Chen, Y. H., & Hsueh, P. R. (2015). Update on infections caused by Stenotrophomonas maltophilia with particular attention to resistance mechanisms and therapeutic options. Frontiers in microbiology, 6, 893. https://doi.org/10.3389/fmicb.2015.00893
Chawla, K., Vishwanath, S., & Munim, F. C. (2013). Nonfermenting Gram-negative Bacilli other than Pseudomonas aeruginosa and Acinetobacter Spp. Causing Respiratory Tract Infections in a Tertiary Care Center. Journal of global infectious diseases, 5(4), 144–148. https://doi.org/10.4103/0974-777X.121996
Costerton, J. W., Stewart, P. S., & Greenberg, E. P. (1999). Bacterial biofilms: a common cause of persistent infections. Science (New York, N.Y.), 284(5418), 1318–1322. https://doi.org/10.1126/science.284.5418.1318
Crossman, L. C., Gould, V. C., Dow, J. M., Vernikos, G. S., Okazaki, A., Sebaihia, M., Saunders, D., Arrowsmith, C., Carver, T., Peters, N., Adlem, E., Kerhornou, A., Lord, A., Murphy, L., Seeger, K., Squares, R., Rutter, S., Quail, M. A., Rajandream, M. A., Harris, D., … Avison, M. B. (2008). The complete genome, comparative and functional analysis of Stenotrophomonas maltophilia reveals an organism heavily shielded by drug resistance determinants. Genome biology, 9(4), R74. https://doi.org/10.1186/gb-2008-9-4-r74
Damier-Piolle, L., Magnet, S., Brémont, S., Lambert, T., & Courvalin, P. (2008). AdeIJK, a resistance-nodulation-cell division pump effluxing multiple antibiotics in Acinetobacter baumannii. Antimicrobial agents and chemotherapy, 52(2), 557–562. https://doi.org/10.1128/AAC.00732-07
Depoorter, E., De Canck, E., Peeters, C., Wieme, A. D., Cnockaert, M., Zlosnik, J. E. A., LiPuma, J. J., Coenye, T., & Vandamme, P. (2020). Burkholderia cepacia Complex Taxon K: Where to Split?. Frontiers in microbiology, 11, 1594. https://doi.org/10.3389/fmicb.2020.01594
Figueiredo, S., Bonnin, R. A., Poirel, L., Duranteau, J., & Nordmann, P. (2012). Identification of the naturally occurring genes encoding carbapenem-hydrolysing oxacillinases from Acinetobacter haemolyticus, Acinetobacter johnsonii, and Acinetobacter calcoaceticus. Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases, 18(9), 907–913. https://doi.org/10.1111/j.1469-0691.2011.03708.x
Gaspar, M. C., Couet, W., Olivier, J. C., Pais, A. A., & Sousa, J. J. (2013). Pseudomonas aeruginosa infection in cystic fibrosis lung disease and new perspectives of treatment: a review. European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology, 32(10), 1231–1252. https://doi.org/10.1007/s10096-013-1876-y
Gbejuade, H. O., Lovering, A. M., & Webb, J. C. (2015). The role of microbial biofilms in prosthetic joint infections. Acta orthopaedica, 86(2), 147–158. https://doi.org/10.3109/17453674.2014.966290
Gil-Gil, T.; Martinez, J.L.; Blanco, P. Mechanisms of antimicrobial resistance in Stenotrophomonas maltophilia: A review of current knowledge. Expert Rev. Anti. Infect. Ther. 2020, 18, 335–347.
Gokale, S.K. and Metgud, S.C. (2010) Characterization and Antibiotic Sensitivity Pattern of Non-Fermenting Gram Negative Bacilli from Various Clinical Samples in a Tertiary Care Hospital, Belgaum. Journal of Pharmaceutical and Biomedical Science, 17, 2230-7885.
Høiby, N., Ciofu, O., & Bjarnsholt, T. (2010). Pseudomonas aeruginosa biofilms in cystic fibrosis. Future microbiology, 5(11), 1663–1674. https://doi.org/10.2217/fmb.10.125
Isler, B., Kidd, T. J., Stewart, A. G., Harris, P., & Paterson, D. L. (2020). Achromobacter Infections and Treatment Options. Antimicrobial agents and chemotherapy, 64(11), e01025-20. https://doi.org/10.1128/AAC.01025-20
Karaiskos, I., Souli, M., Galani, I., & Giamarellou, H. (2017). Colistin: still a lifesaver for the 21st century?. Expert opinion on drug metabolism & toxicology, 13(1), 59–71. https://doi.org/10.1080/17425255.2017.1230200
Kaye, K. S., Pogue, J. M., Tran, T. B., Nation, R. L., & Li, J. (2016). Agents of Last Resort: Polymyxin Resistance. Infectious disease clinics of North America, 30(2), 391–414. https://doi.org/10.1016/j.idc.2016.02.005
Kc, R., Adhikari, S., Bastola, A., Devkota, L., Bhandari, P., Ghimire, P., Adhikari, B., Rijal, K. R., Banjara, M. R., & Ghimire, P. (2019). Opportunistic Respiratory Infections in HIV Patients Attending Sukraraj Tropical and Infectious Diseases Hospital in Kathmandu, Nepal. HIV/AIDS (Auckland, N.Z.), 11, 357–367. https://doi.org/10.2147/HIV.S229531
Kunakom, S., & Eustáquio, A. S. (2019). Burkholderia as a Source of Natural Products. Journal of natural products, 82(7), 2018–2037. https://doi.org/10.1021/acs.jnatprod.8b01068
Magnet, S., Courvalin, P., & Lambert, T. (2001). Resistance-nodulation-cell division-type efflux pump involved in aminoglycoside resistance in Acinetobacter baumannii strain BM4454. Antimicrobial agents and chemotherapy, 45(12), 3375–3380. https://doi.org/10.1128/AAC.45.12.3375-3380.2001
McGowan J. E., Jr (2006). Resistance in nonfermenting gram-negative bacteria: multidrug resistance to the maximum. The American journal of medicine, 119(6 Suppl 1), S29–S70. https://doi.org/10.1016/j.amjmed.2006.03.014
Mellmann, A., Bimet, F., Bizet, C., Borovskaya, A. D., Drake, R. R., Eigner, U., Fahr, A. M., He, Y., Ilina, E. N., Kostrzewa, M., Maier, T., Mancinelli, L., Moussaoui, W., Prévost, G., Putignani, L., Seachord, C. L., Tang, Y. W., & Harmsen, D. (2009). High interlaboratory reproducibility of matrix-assisted laser desorption ionization-time of flight mass spectrometry-based species identification of nonfermenting bacteria. Journal of clinical microbiology, 47(11), 3732–3734. https://doi.org/10.1128/JCM.00921-09
Nicodemo, A. C., Araujo, M. R., Ruiz, A. S., & Gales, A. C. (2004). In vitro susceptibility of Stenotrophomonas maltophilia isolates: comparison of disc diffusion, Etest and agar dilution methods. The Journal of antimicrobial chemotherapy, 53(4), 604–608. https://doi.org/10.1093/jac/dkh128
Pang, Z., Raudonis, R., Glick, B. R., Lin, T. J., & Cheng, Z. (2019). Antibiotic resistance in Pseudomonas aeruginosa: mechanisms and alternative therapeutic strategies. Biotechnology advances, 37(1), 177–192. https://doi.org/10.1016/j.biotechadv.2018.11.013
Poirel, L., Rodriguez-Martinez, J. M., Plésiat, P., & Nordmann, P. (2009). Naturally occurring Class A ss-lactamases from the Burkholderia cepacia complex. Antimicrobial agents and chemotherapy, 53(3), 876–882. https://doi.org/10.1128/AAC.00946-08
Power, R. F., Linnane, B., Martin, R., Power, N., Harnett, P., Casserly, B., O'Connell, N. H., & Dunne, C. P. (2016). The first reported case of Burkholderia contaminans in patients with cystic fibrosis in Ireland: from the Sargasso Sea to Irish Children. BMC pulmonary medicine, 16(1), 57. https://doi.org/10.1186/s12890-016-0219-z
Ramirez, M. S., Bonomo, R. A., & Tolmasky, M. E. (2020). Carbapenemases: Transforming Acinetobacter baumannii into a Yet More Dangerous Menace. Biomolecules, 10(5), 720. https://doi.org/10.3390/biom10050720
Rello, J., Kalwaje Eshwara, V., Lagunes, L., Alves, J., Wunderink, R. G., Conway-Morris, A., Rojas, J. N., Alp, E., & Zhang, Z. (2019). A global priority list of the TOp TEn resistant Microorganisms (TOTEM) study at intensive care: a prioritization exercise based on multi-criteria decision analysis. European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology, 38(2), 319–323. https://doi.org/10.1007/s10096-018-3428-y
Sánchez M. B. (2015). Antibiotic resistance in the opportunistic pathogen Stenotrophomonas maltophilia. Frontiers in microbiology, 6, 658. https://doi.org/10.3389/fmicb.2015.00658
Sader, H. S., & Jones, R. N. (2005). Antimicrobial susceptibility of uncommonly isolated non-enteric Gram-negative bacilli. International journal of antimicrobial agents, 25(2), 95–109. https://doi.org/10.1016/j.ijantimicag.2004.10.002
Samonis, G., Vardakas, K. Z., Kofteridis, D. P., Dimopoulou, D., Andrianaki, A. M., Chatzinikolaou, I., Katsanevaki, E., Maraki, S., & Falagas, M. E. (2014). Characteristics, risk factors and outcomes of adult cancer patients with extensively drug-resistant Pseudomonas aeruginosa infections. Infection, 42(4), 721–728. https://doi.org/10.1007/s15010-014-0635-z
Santajit, S., & Indrawattana, N. (2016). Mechanisms of Antimicrobial Resistance in ESKAPE Pathogens. BioMed research international, 2016, 2475067. https://doi.org/10.1155/2016/2475067
Sanz-García, F., Alvarez-Ortega, C., Olivares-Pacheco, J., Blanco, P., Martínez, J. L., & Hernando-Amado, S. (2019). Analysis of the Pseudomonas aeruginosa Aminoglycoside Differential Resistomes Allows Defining Genes Simultaneously Involved in Intrinsic Antibiotic Resistance and Virulence. Antimicrobial agents and chemotherapy, 63(5), e00185-19. https://doi.org/10.1128/AAC.00185-19
Sanz-García, F., Hernando-Amado, S., & Martínez, J. L. (2022). Evolution under low antibiotic concentrations: a risk for the selection of Pseudomonas aeruginosa multidrug-resistant mutants in nature. Environmental microbiology, 24(3), 1279–1293. https://doi.org/10.1111/1462-2920.15806
Senol E. (2004). Stenotrophomonas maltophilia: the significance and role as a nosocomial pathogen. The Journal of hospital infection, 57(1), 1–7. https://doi.org/10.1016/j.jhin.2004.01.033
Sharan, H., Katare, N., Pandey, A., Bhatambare, G. S., & Bajpai, T. (2016). Emergence of Hospital Acquired Carbapenem Resistant Non-Fermenters in Teaching Institute. Journal of clinical and diagnostic research : JCDR, 10(12), DC20–DC23. https://doi.org/10.7860/JCDR/2016/22607.9020
Silby, M. W., Winstanley, C., Godfrey, S. A., Levy, S. B., & Jackson, R. W. (2011). Pseudomonas genomes: diverse and adaptable. FEMS microbiology reviews, 35(4), 652–680. https://doi.org/10.1111/j.1574-6976.2011.00269.x
Tada, T., Miyoshi-Akiyama, T., Dahal, R. K., Mishra, S. K., Shimada, K., Ohara, H., Kirikae, T., & Pokhrel, B. M. (2014). Identification of a novel 6'-N-aminoglycoside acetyltransferase, AAC(6')-Iak, from a multidrug-resistant clinical isolate of Stenotrophomonas maltophilia. Antimicrobial agents and chemotherapy, 58(10), 6324–6327. https://doi.org/10.1128/AAC.03354-14
Toleman, M. A., Bennett, P. M., Bennett, D. M., Jones, R. N., & Walsh, T. R. (2007). Global emergence of trimethoprim/sulfamethoxazole resistance in Stenotrophomonas maltophilia mediated by acquisition of sul genes. Emerging infectious diseases, 13(4), 559–565. https://doi.org/10.3201/eid1304.061378
Turner, K. H., Everett, J., Trivedi, U., Rumbaugh, K. P., & Whiteley, M. (2014). Requirements for Pseudomonas aeruginosa acute burn and chronic surgical wound infection. PLoS genetics, 10(7), e1004518. https://doi.org/10.1371/journal.pgen.1004518
Uppalapati, S. R., Sett, A., & Pathania, R. (2020). The Outer Membrane Proteins OmpA, CarO, and OprD of Acinetobacter baumannii Confer a Two-Pronged Defense in Facilitating Its Success as a Potent Human Pathogen. Frontiers in microbiology, 11, 589234. https://doi.org/10.3389/fmicb.2020.589234
Verweij, P. E., Meis, J. F., Christmann, V., Van der Bor, M., Melchers, W. J., Hilderink, B. G., & Voss, A. (1998). Nosocomial outbreak of colonization and infection with Stenotrophomonas maltophilia in preterm infants associated with contaminated tap water. Epidemiology and infection, 120(3), 251–256. https://doi.org/10.1017/s0950268898008735
Weber, B. S., Harding, C. M., & Feldman, M. F. (2015). Pathogenic Acinetobacter: from the Cell Surface to Infinity and Beyond. Journal of bacteriology, 198(6), 880–887. https://doi.org/10.1128/JB.00906-15
Wolter, D. J., & Lister, P. D. (2013). Mechanisms of β-lactam resistance among Pseudomonas aeruginosa. Current pharmaceutical design, 19(2), 209–222.
Yamamoto, M., Nagao, M., Hotta, G., Matsumura, Y., Matsushima, A., Ito, Y., Takakura, S., & Ichiyama, S. (2012). Molecular characterization of IMP-type metallo-β-lactamases among multidrug-resistant Achromobacter xylosoxidans. The Journal of antimicrobial chemotherapy, 67(9), 2110–2113. https://doi.org/10.1093/jac/dks179
Zelenitsky, S. A., Iacovides, H., Ariano, R. E., & Harding, G. K. (2005). Antibiotic combinations significantly more active than monotherapy in an in vitro infection model of Stenotrophomonas maltophilia. Diagnostic microbiology and infectious disease, 51(1), 39–43. https://doi.org/10.1016/j.diagmicrobio.2004.09.002