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Multi-drug Resistant Gram negative bacteria

Multidrug-resistant Gram-negative bacteria (MDRGN) pose a serious threat to patients. They are resistant not only to β-lactam antibiotics but may also be resistant to other groups of antibiotics, e.g. fluoroquinolones and aminoglycosides and can be  a part of the normal intestinal flora. The patients carrying these organisms can serve as reservoirs responsible for the spread and outbreaks of infection in both the community and the hospital.

The most common MDRGN bacteria which are extensively resistant to antibiotics belong to the Enterobacterales family (Escherichia coli, Klebsiella spp., Serratia spp., Citrobacter freundii, Enterobacter spp., etc.) and non- Enterobacterales Gram-negative bacteria, e.g. Pseudomonas aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia.

Extended-spectrum beta-lactamases (ESBL)

Due to the increasing use and misuse of broad-spectrum antibiotics worldwide, there has been a massive rise in the emergence of ESBL. The first reports of ESBLs in Gram-negative bacilli came from Europe, were quickly followed by reports from the USA and are now recognised worldwide. These organisms tend to spread from patient to patient and represent a major threat due to the spread of mobile genetic element plasmids or transposons that can also confer resistance to various classes of other antibiotics. As a result, ESBL infections are mainly treated with the carbapenem group of antibiotics, i.e. meropenem, imipenem, ertapenem, or doripenem.

Carbapenem-resistant Enterobacterales (CRE)

The increased use and misuse of carbapenems have led to an increase in the emergence of carbapenem-resistant organisms (CRO). Infections with carbapenem-resistant Enterobacteralese (CRE) are often treated with IV colistin. In 2015, colistin resistance in E. coli (both in animals and humans) was reported bringing the threat of the end of the antibiotic era as no new class of antibiotics has been developed against Gram-negative bacteria in the last three decades.

The spread of CRE is a global threat as they are now widely prevalent in most countries. In addition, numerous outbreaks have been reported in individual healthcare facilities (HCFs) worldwide, and even a countrywide outbreak of CRE has been reported in Israeli hospitals. As the choice of treatment is limited, the result, prevention and control of CRE must be taken very seriously by all HCFs.

Non- Enterobacterales Gram-negative bacteria

Acinetobacter baumannii: Acinetobacter spp. is present in soil, sewage, and water. In a healthcare setting, most human infections are caused by  A. baumannii. Although an organism of low pathogenicity, it has become a significant cause of hospital-acquired infections because of its remarkable ability to survive and spread in the hospital environment and rapidly acquire resistance determinants to a wide range of antibiotics.

The risk of transmission of A. baumannii is higher in intensive care units than in the wards because most of these patients have multiple risk factors and have increased patient contact with healthcare workers to provide care. Once acquired, the organism is carried for prolonged periods and is increasingly seen in dry environments (e.g. bed linen, mattresses, pillows, fans, and cupboard surfaces), as well as in wet environments (e.g. on plastic tubing, pressure monitors, sinks, ventilators, cleaning cloths, and face flannels). Patient-to-patient transmission can occur via contaminated items, equipment, and especially high-touch environmental surfaces.

  1. baumanniiinfections are more common in warm and humid climates and, in the summer months, in temperate countries. Once endemic, the organisms are very difficult to eradicatebecause of biofilm formation. Therefore repeated thorough cleaning and disinfection of the environment and decontamination of  items and equipment is essential.

Pseudomonas aeruginosa is an opportunistic pathogen responsible for causing various infections, especially in immunocompromised patients. P.aeruginosa is an environmental organism that can spread to people in healthcare settings, particularly when exposed to contaminated water or contaminated aqueous products. In hospitalised patients, it mainly infects those intubated and undergoing mechanical ventilation and those with indwelling devices, such as urinary catheters. In addition, it has also been responsible for outbreaks in neonatal units.

Stenotrophomonas maltophilia is widespread in water, soil, plants, animals, and sewage. Currently, little is known about the virulence factors, but it is an organism of low pathogenicity. Infections are infrequent but more common in patients with multiple risk factors. In addition, treatment with other broad-spectrum antibiotics, especially prior therapy with carbapenems, has been identified as an important predisposing factor.

References and further reading   

  • Carbapenem-Resistant Enterbacteriaceae (CRE) Control and Prevention Toolkit. Rockville: Agency for Healthcare Research and Quality, US Department of Health and Human Services, 2014.

Carbapenem-Resistant Enterbacteriaceae (CRE) Control and Prevention Toolkit (

  • 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.

  • Infection prevention and control measures and tools for the prevention of entry of carbapenem-resistant Enterobacteriaceae into healthcare settings: guidance from the European Centre for Disease Prevention and Control. Antimicrob Resist Infect Control 2017, 6:113.

  • Hawkey PM, Warren RE, Livermore DM, et al. Treatment of infections caused by multidrug-resistant Gram-negative bacteria: report of the British Society for Antimicrobial Chemotherapy/Healthcare Infection Society/British Infection Association Joint Working Party. J Antimicrob Chemother 2018,73 (Suppl 3):iii2–iii78.

  • Health Technical Memorandum 04-01. Safe water in healthcare premises: Part A – Design, installation and commissioning. London: Dept. of Health, 2016.

  • Health Technical Memorandum 04-01.Safe water in healthcare premises – Part B: Operational management. London: Dept. of Health, 2016.

  • Health Technical Memorandum 04-01.Safe water in healthcare premises: Part C – Pseudomonas aeruginosa – advice for augmented care units. London: Dept. of Health,2016.

  • Health Technical Memorandum 04-01: Supplement: Performance specification D 08: thermostatic mixing valves (healthcare premises). London: Dept. of Health,2017.

  • Prevention and control of multi-drug-resistant Gram-negative bacteria: recommendations from a Joint Working Party. J Hosp Infect,92(Supplement 1): S1–44.

  • Toolkit for the Early Detection, Management and Control of Carbapenemase-producing Enterobacteriaceae in Scottish Acute Settings. Health Protection Scotland,2019.

  • Independent Review of Incidents of Pseudomonas aeruginosa Infection in Neonatal Units in Northern Ireland. Belfast: The Regulation and Quality Improvement Authority,2012.

  • Schwaber MJ, Lev B, Israeli A, et al. Containment of a countrywide outbreak of carbapenem-resistant Klebsiella pneumoniaein Israeli hospitals via a nationally implemented intervention. Clin Infect Dis 2011; 52(7):848–55.
  • Solter E, Adler A, Rubinovitch B, et al. Israeli national policy for carbapenem-resistant Enterobacteriaceae screening, carrier isolation and discontinuation of isolation. Infect Control Hosp Epidemiol 2018; 39(1):85–9.

  • Guidelines for the Prevention and Control of Carbapenem-resistant Enterobacteriaceae, Acinetobacter baumannii and Pseudomonas aeruginosa in Health Care Facilities. Geneva: World Health Organization, 2017.

  • Implementation manual to prevent and control the spread of carbapenem-resistant organisms at the national and health care facility level. Geneva: World Health Organization,2019.