"Let's Increase the Use of Tetracyclines to Decrease C. difficile colitis" by Steven P. LaRosa, M.D.

Physicians are quite comfortable with the use of the tetracycline antibiotics Doxycycline and Minocycline in tickborne infections and acne. Short of these two indications this class of antibiotics is rarely reached for. A new study by Raseen Tariq and colleagues in Clinical Infectious Disease 2018;66(4):514-522 should change that. A meta-analysis of 6 studies demonstrated that tetracyclines were associated with a decreased risk of C diff Infection (CDI) (odds ratio 0.62, 95% CI , 0.40-0.81; p < .001. This decreased risk held when just Doxycycline was examined. There are at least 2 potential biologic explanations for this observed effect. The first is that tetracycyclines cause fewer and shorter lasting perturbations to the fecal microbiota than other classes of antibiotics. The second is that enteral delivery of tetracyclines has inhibitory effect on Clostridium difficile. In fact, Tigecycline, a glyclcycline relative of tetracyclines, has been used successfully as a salvage therapy in cases of severe C diff colitis.

How then can we leverage this beneficial effect of tetracyclines on the development of C diff infection into clinical practice? In patients with a recent history of C diff colitis or recurrent C diff colitis who have a need for "abdominal coverage" for a concomitant infection I have used Tigecycline. For upper respiratory infections including sinusitis and COPD exacerbations one can successfully prescribe Doxycycline instead of antibiotics commonly associated with development of CDI including Amoxicillin-clavulanic acid, cephalosporins and respiratory fluoroquinolones. In Community acquired pneumonia (CAP) coverage of pathogens including Mycoplasma pneumoniae, Chlamydiophila pneumoniae and Legionella pneumophila can be accomplished with Doxycycline rather than Azithromycin or respiratory fluoroqinolones. In hospitalized patients I have often given doxycycline + Ampicillin/Sulbactam thereby avoiding the high risk third generation Cephalosporin Ceftriaxone as well. In skin and soft tissue infections, minocycline is very effective in the treatment of abscesses due to MRSA and can be used instead of Clindamycin, a high risk agent for the development of CDI.

An additional under appreciated area that tetracycline use can be increased is in the treatment of non-systemic urinary tract infections. The credit for bringing attention to this area needs to go to Burke Cunha ( Eur J Clin Microbiol Infect Dis 2012;31:2865-2868). In this paper Dr. Cunha points out that MICs and susceptibility testing done for common urinary pathogens including Pseudomonas and enteric Gram negative rods (E. coli, Klebsiella, Proteus and Enterobacter) are based upon serum levels of drugs and not urine concentrations. As such these organisms are either reported as resistant to Tetracyclines or the test is not done. The urinary concentrations however of doxycycline in a patient with reasonable renal function are far in excess of what is needed for microbial killing of these organisms. It is not unreasonable to use doxycline in non-systemic UTIs and follow the patient clinically and for resolution of pyuria on UA and thus avoid the use of Fluoroquinolones and Cephalosporins. One additional caveat is that patients should receive a loading dose of either Doxycline or Monocycline to avoid failure associated with needing 5 1/2 lives to achieve steady state levels.

So remember, Tetracyclines are not just for tickborne infections and acne and can be a good friend in preventing infections due to Clostridium difficile infections!