Clindamycin Antibiotic Resistance Concerns

Introduction

Source: clindamycin
  • Overview of Clindamycin
    • Clindamycin is a potent Lincosamide antimicrobial that is approved by FDA to treat skin infections, intra-abdominal infections, bone infections, and gynecological infections. According to IDSA and ASHP, doctors also use clindamycin as prophylaxis in surgical procedures.
    • In general, antibiotics are important in treating bacterial infections that can be fatal if not treated in a timely manner. Unfortunately, overuse of these agents has led to resistance of these pathogens due to unwanted exposure. This article explores clindamycin antibiotics along with its resistance concerns.  

Understanding Antibiotic Resistance

  • What is Antibiotic Resistance?
    • Bacteria resist antibiotics through a mechanism known as antibiotic resistance. The antibiotics are used to kill (bactericidal) or inhibit the bacterial growth (bacteriostatic). 
    • Bacteria can develop resistance through: (1) Drug Efflux Pumps (2) Enzymatic Inactivation (3) Target Modification (4) Reduced Drug Uptake.
    • Global impact and statistics: In 2019, antibiotic resistance caused approximately 1.27 million deaths worldwide and contributed to 4.95 million deaths. By 2050, experts estimate it will cause around 10 million deaths annually.  
  • Factors Contributing to Antibiotic Resistance
    • Overuse and misuse of antibiotics in humans and animals has led to drug-resistant pathogens. 
    • Lack of new antibiotic development. There is inadequate research necessitating urgency for new drugs, and to ensure easy access to these drugs.

Clindamycin: Mechanism of Action

  • How Clindamycin Works
    • Bacteriostatic vs. bactericidal properties: Depending on concentration, site of infection, and organism involved clindamycin can be bactericidal or bacteriostatic. Lower concentration of Clindamycin has bacteriostatic action, and higher concentration exhibits bactericidal action. 
    • Common bacterial targets: Clindamycin works by reversibly binding to 50s ribosomal subunits thereby inhibiting peptide bond formation and protein synthesis. Clindamycin is used against Gram positive pathogens: Staphylococcus aureus (methicillin-susceptible strains), Streptococcus pneumoniae (penicillin-susceptible strains), and Streptococcus pyogenes.

Clindamycin Resistance: Current Concerns

  • Prevalence of Clindamycin Resistance
    • Statistics and trends: Globally Clindamycin resistance against S. aureus can range from 10-50 % depending on the region and specific bacterial strains.
    • Geographic variations: Northeast parts of the US have slightly higher rates of resistance to clindamycin than other parts of the US. Europe has differences in resistance patterns with some countries having higher resistance rates. Asia has higher resistance rates in certain regions due to widespread use of antibiotics in healthcare and agriculture.     
  • Mechanisms of Resistance
    • Genetic mutations: Mutations of 23s rRNA bases are responsible for bacterial resistance against Clindamycin. Clindamycin has been used to treat infections by Methicillin Resistant Staphylococcus Aureus (MRSA). However, emergence of resistance with clindamycin has reduced its use by physicians. 

Clinical Implications of Clindamycin Resistance

  • Impact on Treatment Efficacy
    • Case studies: In 1969, McGehee et al reported two cases of erythromycin-resistant S. aureus where clindamycin was used as an alternative but proved ineffective. Rao listed three case reports where clindamycin was initially effective but led to relapses, making it ultimately ineffective. Frank et al reported 33 cases of S. aureus resistance in pediatric patients, but clindamycin was used to treat only two of these cases and was found to be ineffective.
    • Alternative treatment options: Based on Infection types, bacterial strains, and patient factors:
  1. Antibiotics: Doxycycline (MRSA), Amoxicillin (Skin and respiratory infections), Trimethoprim/Sulfamethoxazole (UTI and Pneumonia), Azithromycin, Linezolid (MRSA), Ceftaroline (MRSA).
  2. Non-Antibiotics: Surgical Options (Incision and Drainage).
  • Challenges in Managing Resistant Infections
    • Increased healthcare costs: according to World Bank, the healthcare cost for management of antibiotic resistance can increase to 1 trillion $ by 2050, and  1 to 3.4 trillion $ in GDP losses per year by 2030
    • Longer hospital stays and recovery times: antibiotic resistance can be harder to treat thereby increasing the hospital stay and cost.

Strategies to Combat Clindamycin Resistance

  • Antibiotic Stewardship Programs
    • Guidelines for appropriate use: Antibiotic stewardship program (ASP) aims to optimize the use of antibiotics to combat resistance. The guidelines for appropriate use of antibiotics include: (1) Right drug, (2) Right dose, (3) Right duration, (4) Right route.
    • Role of healthcare providers: The hospital’s clinical pharmacists, microbiologists, infectious disease physicians, and nurses initiate the ASP. The major role of this team is to provide education and training, monitoring and feedback, patient education, and Infection control. 
  • Research and Development
    • New antibiotics and alternative therapies: latest technologies like machine learning and AI have paved the way for development of new agents for treatment. Abaucin is the latest antibiotic that is being developed through ML and AI. 
    • Innovations in diagnostic tools: AI integration into diagnostic machines helps technologists and physicians in accurately diagnosing diseases in a timely manner to ensure faster treatment especially in case of bacterial infections.

Conclusion

Clindamycin is a lincosamide antibiotic that is used to treat infections caused by gram positive bacterias like S. Aureus. However, unwanted use of this antibiotic has led to resistance of the bacterias (MRSA). Therefore, it is important to provide strategies like antibiotic stewardship programs to impart responsible use of antibiotics. Furthermore, research and development of new agents for treating the deadly resistant bacterias are necessary, demanding faster recovery and reducing cost of treatment.   

References

  1. Inducible Clindamycin Resistance in Staphylococci: Should Clinicians and Microbiologists be Concerned? | Clinical Infectious Diseases | Oxford Academic (oup.com)
  2. Clindamycin – StatPearls – NCBI Bookshelf (nih.gov)
  3. Antibiotic resistance | Definition, Mechanisms, Examples, & Facts | Britannica
  4. Antimicrobial resistance (who.int)
  5. Clindamycin: An overview – UpToDate
  6. ResistanceMap (onehealthtrust.org)
  7. Top clindamycin (Cleocin) alternatives and how to switch your Rx (singlecare.com)
  8. Core Elements of Antibiotic Stewardship | Antibiotic Prescribing and Use | CDC

Written By: Ayoob Mansoor, PharmD, RPh

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