Multidrug-Resistant Gram-Negative Bacilli (MDR-GNB)

  Gram-negative bacilli have been a source of healthcare-associated infections for many years and may be found in patients in virtually all healthcare settings as either infection or colonization. In recent years, multidrug-resistant gram-negative organisms have increased in nearly all healthcare settings. Though resistance to any class of antibiotic can occur, it occurs mainly among the extended spectrum beta-lactam antimicrobial agents. This is mainly due to the ability of these organisms to produce extended spectrum beta lactamase enzymes (ESBLs), which make them highly resistant to many of the extended spectrum beta-lactam agents such as the penicillins, cephalosporins, and monobactams. This group includes primarily, Klebsiella, E. coli, P. aeruginosa, and other Enterobacteriaceae, though numerous other drug-resistant gram-negative bacteria strains have also been reported.

 ESBL-producing gram-negative organisms and carbapenemase-producing enterobacteriaceae are a group of emerging infectious pathogens that warrant inclusion in institutional infection control policies. The HICPAC/CDC MDRO 2006 Guidelines recommend contact precautions and other tier 2, intensified control efforts when cases of MDR-GNB are identified. Two of the significant MDR-GNB include:

 1. Acinetobacter baumannii

In recent years, multidrug-resistant A. baumannii (MDRAb) has increased in prominence as a healthcare-associated pathogen. Primarily affecting hospital ICU’s, A. baumannii is associated with longer hospitalizations, greater economic cost, and increased morbidity. Infection due to MDRAb can occur sporadically, but is more commonly associated with outbreaks. MDRAb infections typically manifest as respiratory (ventilator pneumonia), urinary tract, and wound infections (including burn wounds). High rates of bacteremia have also been reported in military service members injured in the Middle East. MDRAb is an ESBL-producing gram-negative bacilli that routinely exhibit resistance to multiple classes or even all classes of antimicrobial drugs leading to greater difficulty in treatment.

A. baumannii is a ubiquitous gram-negative bacillus, found in soil, water, animals, and humans. In the clinical setting, individuals may be infected or colonized and environmental surfaces may be contaminated by A. baumannii where its ability to persist may contribute to transmission between patients, as well as long-term outbreaks. Primarily associated with acute care and long-term acute care facilities, it is now encountered in LTC facilities with increasing frequency. The epidemiology of MDRAb indicates that this is an emerging pathogen and all types of healthcare facilities should be knowledgeable of this pathogen and recommended control measures.

 2. Klebsiella pneumoniae and other Carbapenemase-Producing Enterobacteriaceae

Klebsiella pneumoniae and other gram-negative bacilli have been increasing in clinical importance. While ESBL production among the gram-negative organisms has been an infection control issue for many years, more recently strains of enteric bacilli and other gram-negative organisms have demonstrated production of carbapenemases (beta-lactamase enzymes mediating resistance to the extended spectrum cephosporins as well as carbapenem antibiotics, e.g.,impenem, ertapenem, meropenem).

 In the U.S., a type of carbapenemase referred to as KPC (Klebsiella pneumoniae carbapenemase) has been demonstrated in several species of enteric bacilli but is most commonly found in strains of Klebsiella pneumoniae. A KPC-producing strain of Klebsiella pneumoniae was first reported in North Carolina in 2001 and another was later discovered as part of an outbreak in New York that began in 2000. KPC producing strains have also been reported sporadically from various parts of the U.S., particularly the east coast,  In addition to the high level of resistance commonly found in the KPC-producing strains, the inability of most laboratories to directly detect or confirm the KPC enzyme through routine testing poses additional concern since KPC production may not be detected through standard susceptibility testing.

Emergence of a New Antibiotic Resistant Organism

Tourist seeking treatment in India, Pakistan, and the UK are bringing home a dangerous type of bacterial infection that is resistant to nearly all antibiotics, according to an article released today in The Lancet (www.lancet.com).  Doctors have identified 29 patients in the United Kingdom (UK) with this new resistant bacteria.  Most of the individuals have traveled to India, Pakistan or Bangladesh for medical procedures, which included cosmetic surgery.  Dozens of patients from Asia have also gotten infected according to the researchers from Cardiff University.  Most of the new infections involved two common bacteria, E. coli or Klebsiella pneumoniae.  In these cases the bacteria aquired a gene that made it resistant to all but one or two known antibiotics.  The gene is named NDM-1 which protects the bacteria by producing an enzyme that destroys the antibiotics.  NDM-1 was first identified last year but researchers have found some cases dating back to 2003.

NDM-1 is resistant to antibiotics that medical professional consider a “last resort” drug against resistance, they are susceptible to colistin, and tigecycline.  Colistin has not been used much since the 1970s because of toxic side effects.  The new strains appear to be widespread in many medical centers in south Asia and have been seen in Canada, Australia, the Netherlands, Sweden and the United States.  CDC identified three cases in June among patients who were infected with bacteria carrying the NDM-1 gene.  All of the infected patients had undergone surgery in India.

The CDC alerted doctors to the possibility of resistant infections in any patient who had received medical treatment in Pakistan or India.  The CDC also recommended that if patients were identified they should be isolated and physicians and nurses should take extra precautions and wear personal protective equipment including fluid resistant gowns and gloves in combination with Standard Precautions.

Although there are only a few cases identified the fact that the new gene is found in different kinds of bacteria is very troubling.  This gives the NDM-1 gene the potential to spread more quickly and more widely than if it were found in only one bacteria.

Researchers have identified 44 isolates with NDM-1 in Chennai, 26 in Haryana, 37 in the UK, and 73 in other sites in India and Pakistan.

The potential of New Delhi Metallo-ß-lactamase 1 (NDM-1) to be a worldwide public health problem is great, and international surveillance is needed.