Superbugs are strains of bacteria that are resistant to most antibiotics. This resistance means that infections caused by superbugs can be extremely difficult to treat. Some of the most well-known types of superbugs include methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococci (VRE), multidrug-resistant Pseudomonas aeruginosa, carbapenem-resistant Enterobacteriaceae (CRE), and extensively drug-resistant Mycobacterium tuberculosis (XDR-TB). Understanding the different types of superbugs and how they develop antibiotic resistance is crucial for controlling their spread and developing new treatments.
What are antibiotics and how do bacteria become resistant?
Antibiotics are drugs that are used to treat bacterial infections. They work by interfering with critical processes in bacteria, killing the bacteria or stopping them from multiplying. Antibiotics have transformed modern medicine, making once deadly infections easily treatable. However, bacteria can evolve resistance to antibiotics through genetic mutations or by acquiring resistance genes from other bacteria. When an antibiotic is used, sensitive bacteria are killed but resistant bacteria can survive and multiply. Over time, resistant strains dominate the bacterial population.
How do superbugs spread?
Superbugs spread the same way as other bacteria – through direct contact with an infected person, contact with contaminated surfaces, consumption of contaminated food or water, or exposure in healthcare settings. However, superbugs tend to spread more easily because infections persist despite antibiotic treatment and standard hygiene and infection control practices. Patients in healthcare facilities are especially vulnerable because superbugs can be passed between patients on the hands of healthcare workers or via contaminated equipment. Poor sanitation and overcrowding facilitates transmission in communities. Global travel enables superbugs to spread between countries rapidly.
Methicillin-resistant Staphylococcus aureus (MRSA)
Staphylococcus aureus is a common type of bacteria that is present on the skin and mucous membranes of around a third of healthy people. It can cause minor skin infections but is also responsible for more serious illnesses such as pneumonia, meningitis and sepsis. Methicillin is an antibiotic that used to be effective against S. aureus but is now rarely used because resistance is so widespread. MRSA infections are resistant to multiple antibiotics, not just methicillin. MRSA was first detected in 1961 and is now prevalent worldwide both in healthcare facilities and the community.
How did MRSA become resistant?
S. aureus carries a gene called mecA that encodes an altered penicillin-binding protein (PBP2a). PBPs are involved in construction of the bacterial cell wall. The altered PBP2a does not bind methicillin or related antibiotics, allowing cell wall synthesis to continue unaffected. The mecA gene is carried on a mobile genetic element called the staphylococcal cassette chromosome mec (SCCmec) which can spread horizontally between S. aureus strains.
Diseases caused by MRSA
- Skin and soft tissue infections – boils, abscesses, infected wounds
- Pneumonia – often hospital-acquired
- Bloodstream infections – can lead to sepsis and shock
- Bone and joint infections – osteomyelitis
- Endocarditis – infection of the heart valves
Transmission
MRSA is spread by direct contact with infected people or surfaces/objects they have touched. Outbreaks occur in crowded settings such as schools, dormitories, military barracks and prisons. Patients can carry MRSA on their bodies without showing symptoms. In hospitals, MRSA spreads via contaminated hands of health care workers or equipment. Poor hygiene practices facilitate transmission.
Treatment
MRSA infections are treated with non-beta lactam antibiotics that the bacteria remains sensitive to, depending on laboratory testing. Options include clindamycin, doxycycline, vancomycin, linezolid and daptomycin. Drainage of abscesses or debridement of infected tissue may be necessary. MRSA decolonization with antiseptic washes and nasal ointment may be used to eliminate carriage and prevent recurrence.
Vancomycin-resistant Enterococci (VRE)
Enterococci are bacteria that naturally inhabit the gastrointestinal tract but can cause infections if they spread to other body sites. Vancomycin was previously effective against Enterococci but VRE strains have acquired resistance. VRE was first seen in 1986 and has become a major cause of healthcare-associated infections. The CDC estimates over 20,000 invasive VRE infections and 1,300 deaths occur in the US annually.
Mechanisms of vancomycin resistance in VRE
- Altered cell wall structure – Lower affinity for vancomycin
- Ligand substitution – Removal of vancomycin binding target
- Enzyme degradation of vancomycin
Diseases caused by VRE
- Urinary tract infections
- Intra-abdominal and pelvic infections
- Bloodstream infections
- Wound infections
- Endocarditis
Transmission
VRE spreads via contaminated hands of healthcare workers or contact with contaminated surfaces and medical equipment. Patients in long-term care facilities and those with long hospital stays are most at risk. VRE can persist for weeks on surfaces. Rates of VRE infection are higher in countries with higher levels of vancomycin use.
Treatment
Treatment options for VRE are limited but include linezolid, daptomycin or quinupristin/dalfopristin. Preventing spread via contact precautions is important. Reducing vancomycin use can help prevent development of resistance.
Multidrug-resistant Pseudomonas aeruginosa
Pseudomonas aeruginosa is a bacterium that can cause serious respiratory, bloodstream and urinary tract infections, particularly in hospital patients with weakened immune systems. It has an intrinsic resistance to many antibiotics and can acquire further resistance through mutation and horizontal gene transfer. Multidrug-resistant strains are a particular problem in ICUs and cystic fibrosis patients.
Mechanisms of antibiotic resistance
- Efflux pumps remove antibiotics from bacterial cells
- Outer membrane porins selective for nutrients over antibiotics
- Chromosomal mutations alter antibiotic target sites
- Biofilm formation makes bacteria less susceptible to antibiotics
Diseases caused by drug-resistant P. aeruginosa
- Ventilator-associated pneumonia
- Catheter-related urinary tract infections
- Surgical site infections
- Infections in cystic fibrosis patients – chronic and difficult to eradicate
Transmission
P. aeruginosa thrives on moist surfaces. In hospitals it colonizes sinks, taps, ventilators, respiratory equipment and cleaning solutions. Patients with weakened immunity are more susceptible to infection. Multi-drug resistant strains easily spread between hospital patients.
Treatment
Combination antibiotic therapy guided by susceptibility testing is used but options are becoming limited. Strict infection control measures are required. Vaccine development is ongoing but challenging due to the bacterium’s adaptability.
Carbapenem-resistant Enterobacteriaceae (CRE)
Enterobacteriaceae are gram-negative bacteria that include Klebsiella, E.coli, Enterobacter, Serratia and Proteus species. They are normal gut bacteria but can cause infections if they spread to other sites. Carbapenems are powerful antibiotics considered last-resort for multi-drug resistant infections. CRE refers to Enterobacteriaceae that produce carbapenemase enzymes that break down carbapenems.
Mechanism of carbapenem resistance
Resistance is mediated by acquired carbapenemase genes, most commonly:
- KPC – Klebsiella pneumoniae carbapenemase
- NDM – New Delhi metallo-beta-lactamase
- VIM – Verona integron-encoded metallo-β-lactamase
- OXA-48 – Oxacillinase-48
Infections caused by CRE
- Bloodstream infections
- Wound infections
- Urinary tract infections
- Pneumonia
- Meningitis
Transmission
CRE readily spread between hospitalized patients on hands of healthcare workers or via contaminated medical equipment. Poor hand hygiene and contact precautions facilitate spread. CRE is difficult to eradicate from hospital environments once established.
Treatment
Colistin is often the only antibiotic still effective against CRE but resistance is rising. Strict infection control and isolation of carriers is crucial. Prevention through antimicrobial stewardship and prudent carbapenem use is paramount.
Extensively drug-resistant Mycobacterium tuberculosis (XDR-TB)
Mycobacterium tuberculosis causes tuberculosis (TB), a disease that most commonly affects the lungs. It is spread by aerosol droplets from infected individuals. XDR-TB strains are resistant to isoniazid and rifampicin (defining MDR-TB) as well as fluoroquinolones and second-line injectable antibiotics.
Mechanisms of drug resistance
- Spontaneous chromosomal mutations
- Overexpression of drug efflux pumps
- Disruption of prodrug activation
- Drug inactivation or modification
Risk factors for XDR-TB
- Failure to complete full course of TB treatment
- Improper prescriptions by providers
- Substandard or counterfeit medications
- Poor disease control programs
Transmission
Airborne transmission through coughing, sneezing or spitting. Prolonged exposure in crowded or poorly ventilated spaces facilitates spread. HIV coinfection accelerates progression to active TB disease.
Treatment
Treatment is difficult and expensive. Older drugs like cycloserine and ethionamide must be used in lengthy regimens. Mortality rates approach 50% in some settings. Prevention through prompt diagnosis and proper treatment adherence is a priority.
How are superbugs being tackled?
The increasing prevalence of superbugs is a major concern for global health. A multi-pronged strategy is required to control their spread and impact:
- Improve sanitation and hygiene to prevent infections
- Introduce stringent infection control in healthcare facilities
- Develop new antibiotics and alternative therapies
- Reduce unnecessary antibiotic use in healthcare and agriculture
- Implement antimicrobial stewardship programs
- Educate healthcare professionals and patients on proper antibiotic use
- Conduct surveillance to monitor resistance trends
- Fund research into new diagnostics, vaccines and treatments
- Increase epidemiological tracking to trace spread of infections
Conclusion
Antibiotic resistance is an evolutionary process whereby antibiotic use selects for strains with defensive mechanisms. Misuse and overuse of antibiotics provides ideal conditions for superbugs to develop. Superbugs threaten modern healthcare as common infections could become untreatable and minor procedures too risky. Concerted efforts are needed to prolong the efficacy of existing antibiotics while new therapies are developed. Responsible use of antibiotics and prudent infection control are the best defences against superbugs. Continual research, surveillance and education are crucial to counter the ever-evolving threat of antibiotic resistance.
