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Since Halloween is coming up, we have teamed up with @ideasinmykitchen to discuss a scary subject, antibiotic-resistant bacteria, with these sweet microbe cookies!
What are superbugs?
Superbugs are bacteria that are genetically changed to withstand the effects of most antibiotics used to treat the infections they cause. Yet, the overuse of antibiotics continues to promote their growth. Each year, drug companies spend millions of dollars on research to develop new antibiotics that can combat these resistant strains of bacteria.
We will be reviewing 6 of the highest-ranked superbugs. The Center for Disease Control’s (CDC) Antibiotic Resistance Threats in the United States, 2019 (AR Threats Report), puts these superbugs at the top of their list for serious to urgent threats requiring immediate attention. Each year, at least 2 million people in the United States are reported to have antibiotic-resistant infections. An infection without an antibiotic to treat it can lead to poor prognosis and bad outcomes.
Methicillin-resistant Staphylococcus aureus (MRSA)
Staphylococcus aureus are gram-positive bacteria commonly found on the skin. The first-line antibiotic to treat staph infections was previously an anti-staphylococcal penicillin (methicillin) until the bacteria became resistant, hence the name methicillin-resistant Staphylococcus aureus. Methicillin resistance was developed by acquiring the mecA gene producing an altered penicillin-binding protein, PBP2a, with a lower affinity for beta-lactam antibiotics. The gene enables transpeptidase activity to continue in the presence of beta-lactam antibiotics, allowing the bacteria to replicate as normal.
Use of recreational IV drugs can increase the risk of developing severe and invasive MRSA infections, including endocarditis, bacteremia, and meningitis.
MRSA infections are divided into two categories by source: hospital-acquired (HA-MRSA) secondary to hospitalization, long-term care, dialysis, invasive device, surgery, etc. or community-acquired (CA-MRSA). The antibiotic of choice for MRSA infections varies by the type and site of infection.
|
Hospital-acquired MRSA |
Community-acquired MRSA |
|
Vancomycin Daptomycin Linezolid Ceftaroline Telavancin Dalbavancin Oritavancin |
Sulfamethoxazole/Trimethoprim Doxycycline Minocycline Clindamycin Linezolid |
Vancomycin-resistant Enterococci (VRE)
Enterococci are gram-positive bacteria that include Enterococcus faecalis and Enterococcus faecium, typically found in the human intestines and female genital tract. E. faecium accounts for more than 70% of VRE strains. Enterococci resistance develops through the gene van A, and leads to resistance to vancomycin, the mainstay antibiotic for Enterococci infections.
The most common infections caused by VRE include wound infections, bacteremia, and urinary tract infections (UTIs). Other serious infections include endocarditis and meningitis. Antibiotic treatment options vary by severity, site of infection, and susceptibilities.
|
Primary Antibiotic Treatments |
Alternative Antibiotic Treatments |
|
Ampicillin Gentamicin* Linezolid Daptomycin |
Doxycycline Nitrofurantoin+ Fosfomycin+ Chloramphenicol Tigecycline Quinupristin/dalfopristin |
ESBL-producing Enterobacteriaceae
Enterobacteriaceae (also called Enterobacterales) is a family of gram-negative bacteria that commonly cause infections in the healthcare setting. Examples of bacteria in this family include Escherichia coli, Proteus mirabilis, and Klebsiella pneumonia.
Enterobacteriaceae can develop resistance by producing enzymes called extended-spectrum beta-lactamases (ESBLs) that break down and destroy commonly used beta-lactam antibiotics such as penicillins and cephalosporins. Treatment of ESBL-producing Enterobacteriaceae can be challenging and depends on the site and severity of infection and local resistance patterns.
|
Antibiotic Treatments |
Clinical Notes |
|
Carbapenems |
Drug of choice*-ertapenem preferred |
|
Piperacillin-tazobactam |
Equivalent to carbapenems in UTI and biliary tract infections |
|
Amoxicillin-clavulanic acid |
Equivalent to carbapenems in UTI and biliary tract infections; convenient for oral switch |
|
Ceftolozone-tazobactam |
Reserved for multi-drug resistant P. aeruginosa infection |
Carbapenem-resistant Enterobacteriaceae (CRE)
Resistance to carbapenems occurs through multiple mechanisms, including carbapenemase enzyme production (enzymes that break down antibiotics), efflux pump-action (carbapenem pumped out of bacteria), and decrease bacteria cell membrane permeability to carbapenem.
Treatment of CRE depends on the site of infection, the type of gram-negative pathogen, resistance profiles. It is essential to consult an infectious disease specialist to assist with appropriate antibiotic regimens as optimal CRE treatment is mostly unknown and based on small retrospective studies. Typical treatment includes an antibiotic backbone coupled with other susceptible antibiotics.
|
Isolate susceptibility |
Drugs |
|
Susceptible to a Beta-lactam |
Backbone: ceftazidime-avibactam (preferred) or meropenem-vaborbactam; alternatively, meropenem (if MIC <8 mg/liter) or ceftazidime or aztreonam PLUS Accompanying drug: colistin, tigecycline, aminoglycoside, or fosfomycin (if isolate intermediate to the backbone drug, consider using 2 of these) |
|
Resistant to all Beta-lactam |
Backbone: colistin PLUS Accompanying drug: tigecycline, aminoglycoside, or fosfomycin |
|
Resistant to all Beta-lactam and colistin |
Backbone: tigecycline or aminoglycoside PLUS Accompanying drug: tigecycline, aminoglycoside, or fosfomycin |
|
Pandrug-resistant or susceptible to only one drug |
Meropenem plus ertapenem or ceftazidime-avibactam plus aztreonam; add any active drug; consider active investigational drug if available |
Pseudomonas aeruginosa
Pseudomonas aeruginosa are gram-negative bacteria common in the community and hospital setting. It is a ‘water-loving’ bug as it is common in swimming pools, whirlpools, hot tubs, sinks, mops, hydrotherapy pools, and humidifiers. As an opportunistic pathogen, it can cause severe infections in critically ill patients in the hospital. Some strains of Pseudomonas aeruginosa may be highly resistant to many antibiotics, including carbapenems. P. aeruginosa can develop antibiotic resistance through lower outer membrane permeability coupled with adaptive genes or mutational processes.
Infections caused by Pseudomonas aeruginosa include pneumonia, bloodstream infections, urinary tract infections, and surgical site infections.
|
IV Antibiotic Treatments |
Oral Antibiotic Treatments |
|
Piperacillin/tazobactam (Zosyn) Ticarcillin/clavulanate (Timentin)* Cefepime Ceftazidime Meropenem Imipenem Tobramycin Gentamicin Amikacin Ciprofloxacin Levofloxacin Aztreonam Colistin |
Ciprofloxacin Levofloxacin Fosfomycin+ |
Clostridioides difficile
Clostridioides difficile (also known as C. diff) are gram-positive toxin-producing anaerobes that commonly causes diarrhea and severe inflammation of the colon (colitis). It is a normal bacterium in the intestines and colon, but can lead to C. diff infections in patients taking antibiotics. Antibiotics disrupt the normal gastrointestinal flora by killing good bacteria leading to an overgrowth of harmful bacteria, such as C. difficile. Higher incidences of C. difficile infection have been associated with antibiotics such as ampicillin, amoxicillin, cephalosporins, clindamycin, and fluoroquinolones.
Other risk factors for C. difficile infections include age greater than 65 years old, recent hospitalization for an extended period, residence in a nursing home, immunocompromise patients, and previous exposure to C. difficile.
The rate of resistance to antimicrobials has significantly increased with this pathogen, limiting treatment options. With these new developments, the Infectious Disease Society of America (IDSA) guidelines updated their recommendation for the treatment of C. difficile in 2018.
|
Clinical Definition |
Recommended Treatment |
|
Initial episode, non-severe* |
Vancomycin 125 mg 4 times a day x 10 days OR Fidaxomicin 200 mg twice daily x 10 days |
|
Initial episode, severe+ |
Vancomycin 125 mg 4 times a day x 10 days OR Fidaxomicin 200 mg twice daily x 10 days |
|
Initial episode, fulminant$ |
Vancomycin 500 mg 4 times a day by mouth or NG tube. If ileus, consider adding vancomycin rectally PLUS IV metronidazole 500 mg every 8 hours |
|
First reoccurrence |
Vancomycin 125 mg 4 times a day x 10 days if metronidazole was used for the initial episode OR Tapered and pulsed dose vancomycin regimen (e.g., 125 mg 4 times per day for 10-14 days; then 2 times per day for a week; and then every 2 or 3 days for 2-8 weeks) OR Fidaxomicin 200 mg twice daily for 10 days if vancomycin used for the initial episode |
|
Second or subsequent reoccurrence |
Vancomycin in a tapered and pulsed regimen OR Vancomycin 125 mg 4 times per day x 10 days followed by rifaximin 400 mg 3 times daily x 20 days OR Fidaxomicin 200 mg twice daily for 10 days OR Fecal microbiota transplantation |
*Leukocytosis with a WBC count <15,000 cells/mL and a serum creatinine level <1.5 mg/dL +Leukocytosis with a WBC count >15,000 cells/mL and a serum creatinine level >1.5 mg/dL $Hypotension or shock, ileus, megacolon
Some patients are colonized with strains of antibiotic-resistant bacteria but do not develop any symptoms. Consider withholding antibiotics in patients who are clinically stable and monitor to decreased the possibility of resistance to the remaining antibiotic options. To prevent the emergence of these multi-drug resistant bacteria, it is important to optimize antibiotic treatments and deescalate as soon as cultures return.
Need to take a break from studying? Find this sugar cookie recipe from @ideasinmykitchen to create your own scary good superbugs!
For more antibiotic study material, check out our Antibiotics Pharmacology Coloring Book!
References and further reading suggestions
- CDC. Antibiotic resistance threats in the United States, 2019. Accessed October 28, 2020. Link.
- Palchak M, Sahni J, Desai N, Randhawa A, Mcginty L, Skirvin JA. Vancomycin-Resistant Enterococcus. USPharmacist. Published August 20, 2014. Link.
- Lister PD, Wolter DJ, Hanson ND. Antibacterial-resistant Pseudomonas aeruginosa: clinical impact and complex regulation of chromosomally encoded resistance mechanisms. Clin Microbiol Rev. 2009;22(4):582-610. doi:10.1128/CMR.00040-09. Link.
- Banawas SS. Clostridium difficile Infections: A Global Overview of Drug Sensitivity and Resistance Mechanisms. Biomed Res Int. 2018;2018:8414257. Published 2018 Feb 21. doi:10.1155/2018/8414257. Link.
- Cho JM, Pardi DS, Khanna S. Update on Treatment of Clostridiodes difficile infection. Mayo Clin Proc. April 202;95(4):758-769. Link.
- Ng K. Updates in the Management of Clostridium Difficile for Adults. USPharmacist. Published April 19, 2019. Link.
- Smith H, Kendall B. Carbapenem-Resistant Enterobacteriacea. Statpearls. Updated July 31, 2020. Link.
- Singleton A, Cluck D. The Pharmacist’s Role in the Treating Extended-Spectrum Beta-Lactamase Infections. USpharmacist. Published April 18, 2019. Link.
