See also bioterrorism agents

Superbugs or bacterial strains which are resistant to antibiotics are becomming a major problem, particularly in hospitals. MRSA alone (below) causes more death each year than HIV/AIDS.

The majority of problematic infections with respect to failing antibiotic treatment is caused by the so called ESCAPE pathogens (acryonym slightly modified form “ESKAPE”) for Enteroccus faecium, S. aureus, Clostridium difficile, Acinetobacter-er baumannili, Pseudomonas aeroginosa and Enterobacteriaceae (incluced E. coli, Klebsiellia pneumoniae, Enterobacterspp). 

Enterrococcus faecium

Vancomycin Resistant Enterococcus becomes dangerous if it gets into your irinary tract or an open wound. VRE is a leading cause of urinary tract infections and meningitis. Mortality rate is about 40%.

S. Aureus (Methicillin Resistant Staphylococcus Aureus (MRSA) )

S. Aureus became a major threat in hospitals due to its high propensity for developing antibiotic resistance and ability to cause a multitude of different infections with high mortality. (Oleksewicz, Archives of Biochemistry and Biophysics 226 (2012) 124-131).

MRSA stands for methicillin resistant  (S. aureus) bacteria. MRSA was first recognized in 1961 about 2 years after the antibiotic methicillin was used to treat S. aureus. MRSA is a resistant strain of S. aureus exhibiting resistance against beta-lactamase penicillins, including methicillin.

The resistance to methicillin is due to a penicillin binding protein coded for by a mobile genetic element called the methicillin resistant gene (mecA). The gene has continued to evolve to the extent that many MRSA strains are currently resistant to several different antibiotics. S. aureus generally produces 4 types of cell wall composing proteins PBPS (penicillin bening proteins) (i.e., PBPS-1 to PBPS-4). However, MRCA produces a new type of PBPS called PBPS-2′. This type of PBP is a specific proteins which has poor affinity against beta-lactam antibiotics and is known to play a central role in the tolerance of this organism.

Signs and Symptoms:

MRSA infections of the skin tend to be raised, red, tender, localized lesions, often featuring pus and feeling hot to touch. They occur easily in breaks in the skin casued by injury, hsaving, or even just abrasion. They may localize around a hair follicle. Feveral is common.

Treansmission:

People become infected with MRSAS by physical contact with people who are infected or carriers (people not infected but who have the bacteria colonized on their body) or by physical contact with MRSAS on any object such as door handles, floors, sinks, or towels. People with a higher risk of MRSA infection include those with obvious skin breaks and those with depressed immune systems (infants, elderly, HIV-infected individuals).

Treatment

Treatment of MRSA often starts with incision of the lesion and drainage of the pus. Antimicrobial treatment should include more than one antibiotic. 

The Vancomycin group of antibiotics represent one of the last lines of defeinse against MRSA. These antiotics interfere with cell-wall biosyntehsis by binding to the D-Ala-D-Ala terminus of the disaccharyl pentapeptide of the peptidoglycan of the bacterial cell wall, resulting in cell death. Recently , however, even vancomycin resistant bacterial have appeared. These bacteria have been identified as having a D-Ala-D-lactate terminus rather than a D-Ala-D-ala terminus of the peptidoglycan. Vancomycin has a much lower affinity for the D-Ala-D-lactate terminus in vancomycin resistant bacterial and consequently makes it less effective as an antibiotic.

S. aureus is a prime target for anti-infective mAb tbased approaches. (Oleksewicz, Archives of Biochemistry and Biophysics 226 (2012) 124-131).

Detection: 

–coagulase test: Staphylococcal coagulase is an enzyme that reacts with factors in plasma to initiate clot formation. In the coagulase test, a tube of plasma is inoculated with the bacterium If it remains liquid, the test is engative. If the plasma develops a lump or becomes completely clotted, the test is postive. 

–genetic tests: The sequence of the mecA gene that codes for PBP-2′ is known. Thus hybridization methods employing a gene specific to mecA gene have been developed to detect MRSA.

Carbapenem-Resistant Bacteria

The emergence of gram-negative pathogens resistant to carbapenem antibiotics is one of the most pressing clinical problems worldwide, particularly when the pathogens produce β-lactamases that have full hydrolyzing activity against carbapenems. Since the description of the first carbapenemase, several of these enzymes, including Klebsiella pneumoniae carbapenemase (KPC), oxacilinase (OXA)-48–like carbapenemase, New Delhi metallo-β-lactamase (NDM), Verona integron–encoded metallo-β-lactamase (VIM), and imipenemase (IMP), have been disseminated globally and are commonly detected in Enterobacterales, Pseudomonas spp., and Acinetobacter spp. The Latin American Network for Antimicrobial Resistance Surveillance (ReLAVRA [Spanish acronym]. was established by the Pan American Health Organization/World Health Organization (PAHO/WHO) in 1996. Its goal is to inform AMR prevention and control policies and interventions in the region through ongoing collection of reliable, comparable, and reproducible AMR data focused on resistance surveillance of community-acquired and nosocomial pathogens. The network currently consists of 33 countries, 19 from Latin America and, since 2018, another 14 from the Caribbean; the organization was renamed ReLAVRA+ to note the additional countries. These countries are represented by their National Reference Laboratories (NRL), officially designated by the national authority in each country. Each NRL, head of the national network, is responsible for external quality control for all participating laboratories, routinely ensuring the reliability of the tests performed, including the validity of species identification and characterization, antibiotic susceptibility tests, and data quality. See Melano CDC

Resistant Acinetobacter Baumannii often occur in immunosuppressed patients such as those having invasive treatments in the hospital. It can cause severe central nervous system infections, meningitis and ventriculitis, especially in patients undergoing head trauma. It is also associated with urinary tract infections and pneumonia. Mortality rate is almost 80%.

Carbapenem-resistant Acinetobacter baumannii (CRAB), an opportunistic pathogen primarily associated with hospital-acquired infections, is an urgent public health threat.  In health care facilities, CRAB readily contaminates the patient care environment and health care providers’ hands, survives for extended periods on dry surfaces, and can be spread by asymptomatically colonized persons; these factors make CRAB outbreaks in acute care hospitals difficult to control.

Resistant E. coli 

Resistant E. coli s associated with gastrointestinal infections and dehydration. It comes from feces of an animal coming into contact with food products. It causes more than 3,000 death per year.

Clostridium Difficile 

Clostridum Difficile s passed in feces and spread to food and other objects when an infected person does not wash his/her hands. The bacteria generates spores which are very difficult to eliminate. It produces toxins that attack the lining of the intestine. Symptoms include diarrhea to inflammation of the colon, which can lead to death. Older adults in hosptials and long term facilities are particularly susceptible. Mortality is up to 25% in elderly persons.

C. difficile is a Gram-positive pathogen and the leading casue of antibiotic-associated diarrhea in the hspital setting. Nosocomial antibiotic assocaited diarrhea is a significant clinical problem with at elast 300 thousand cases eyarly in the US. Disease is caused by intestinal colonization with C. difficile and production of toxins A and B. Both toxins are cytotoxic (with toxin B being more poteint) and toxin A is also an enterotoxin.  (Oleksewicz, Archives of Biochemistry and Biophysics 226 (2012) 124-131).

Treatment

The standard of care is treatment with vancomycine or metronidazole, but relapse occurs in 10-20% of patients after cessation of treatment. and widespread vancomycin use may comproise its utility as a last resort drug.  (Oleksewicz, Archives of Biochemistry and Biophysics 226 (2012) 124-131).

Two human mAbs are currently in clinical development as adjuncts to treatment of antibiotic induced diarrhea in hospitalized patients agaisnt toxin A  and MDX-1388 agaisnt toxin B, developed by Massachusetts Biologic Laboratories/ Medarex/Merck. Both are fullyi human mAbs generated in transgenic mice using immunization with inactivated toxin A or inactivated toxin B combined with a recombinant protein correspoinding to the 590 C-terminal amiho acids of toxin B. (Oleksewicz, Archives of Biochemistry and Biophysics 226 (2012) 124-131).

Enterobacteriaceae

Klebsiellia Pneumoniae

–New Delhi metallobeta-lactamase (NDM-1) is rapidly spreading with infections appearing in both the UK and U.S. It is otherwise known as resistant Klebsiella Pneumonia and often associated with very difficult to treat blood stream infections, surgical site infections and meningitis. It was originally discovered in New Delhi. Mortality rate is over 50%.

Pseudomonas

Resistant Pseudomonas Aeruginosa: Pseudomonas is a type of bacteria (germ) that is found commonly in the environment, like in soil and in water. Of the many different types of Pseudomonas, the one that most often causes infections in humans is called Pseudomonas aeruginosa, which can cause infections in the blood, lungs (pneumonia), or other parts of the body after surgery. In 2017, multidrug-resistant Pseudomonas aeruginosa caused an estimated 32,600 infections among hospitalized patients and 2,700 estimated deaths in the United States. See CDC 

Psuedomonas Aeruginosa is a bacterium found in soil and water. It can get in through the skin and turn deadly. It is particularly serious in patients hospitalized with cancer, cystic fibrosis and burns. Mortality rate is about 50%. Pseudomonas aeruginosa is a common encapsulated, Gram-negative, rod-shaped bacterium that can cause disease in plants and animals, including humans. A species of considerable medical importance, P. aeruginosa is a multidrug resistant pathogen recognized for its ubiquity, its intrinsically advanced antibiotic resistance mechanisms, and its association with serious illnesses – hospital-acquired infections such as ventilator-associated pneumonia and various sepsis syndromes. 

Strains of Pseudomonas aeruginosa are known to utilize their high levels of intrinsic and acquired resistance mechanisms to counter most antibiotics. In addition, adaptive antibiotic resistance of P. aeruginosa is a recently characterized mechanism, which includes biofilm-mediated resistance and formation of multidrug-tolerant persister cells, and is responsible for recalcitrance and relapse of infections. The discovery and development of alternative therapeutic strategies that present novel avenues against P. aeruginosa infections are increasingly demanded and gaining more and more attention. See Cheng

Products of Pinesole have even beenr ecalled due to the present of Pseudomonas aeruginosa (see Consumer Product Safety Commission)

Curcumin as a flavonoid from the rhizome of Curcuma longa has antibacterial, antiviral and antifungal activity. Multidrug resistant non-fermenters are continuously increasing in hospital and ICU settings. One of the mechanisms of developing drug resistance is possession of efflux pump through which bacteria extrude antimicrobial agents and other toxic substances. If these efflux channels are blocked or inhibited, increased drug concentration can be achieved in a bacterial cell with optimal drug dose.  Significant reduction in MIC was observed after adding curcumin (50mg/L) with selected antimicrobial agents in 9/30 (30%) of multi drug resistant (MDR) isolates of Pseudomonas aeruginosa, while no change in MIC was observed when curcumin (50mg/L) was used alone, indicating its efflux pump inhibitor activity. See Mohapatra

Curcumin encapsulated in micellar/polymersome nanoparticles was also shown as an effective efflux pump inhibitor (EPI) on the expression of mexX and oprM genes in curcumin-treated and -untreated isolates of Pseudomonas aeruginosa. Clinical isolates of Pseudomonas aeruginosa were treated with ciprofloxacin (sub-MICs) alone and/or in combination with curcumin-encapsulated in micellar/polymersome nanoparticles. The expression of mexX and oprM genes was quantitatively evaluated by qRT-PCR in curcumin-treated and -untreated bacteria after 24 h. Curcumin-encapsulated in nanoparticles (400 µg/mL) induced cell death up to 50% in ciprofloxacin-treated (1/2MIC) resistant isolates during 24 h, while the bacteria treated with ciprofloxacin (without curcumin) were not inhibited. Also, curcumin in different concentrations increased effect of ciprofloxacin (sub-MICs). Downregulation of mexX and oprM genes was observed in cells treated with curcumin and ciprofloxacin compared to cells treated with ciprofloxacin alone. It seems that curcumin can be used as complementary drug in ciprofloxacin-resistant isolates through downregulating genes involved in efflux pumps and trapping ciprofloxacin on bacterial cells and increasing the effects of drug. See Takrami

Other Dangerous Bacteria

 Resistant Streptococcus is a strain that turns into a flesh eating disease. Mortality is about 28%. The fastest way to treat it is to cut the skin off.