C-diff and Broad-Spectrum Antibiotics
A Cautionary Tale
Infection is a leading cause of death in the complex treatment landscape of myeloma, making broad-spectrum antibiotics critical in combating severe infections. However, these powerful medications carry significant risks, including the potential to trigger Clostridioides difficile (henceforth referred to as “C-diff”) infections, especially in patients with a history of this challenging condition.
C Diff is a bacteria that can live in our guts, but for people treated with specific antibiotics (broad spectrum - capable of killing many different types of bacteria) - the delicate balance of bacteria can be disrupted, resulting in overgrowth of C-Diff and severe infection leading to diarrhea, inflammation, or hospitalization. C-Diff can be very difficult to eradicate completely, and people may continue to have symptoms for weeks to months even after the infection has been treated. More on this later.
Providers must consider a patient's history of C-diff when planning treatment and balance the need for aggressive antibiotic use against the risk of reactivating C-diff.
Patients must understand these risks and be empowered to discuss alternative treatments with their providers, using questions like: “I have a history of C-diff. Is this medication a broad-spectrum antibiotic? Are there safe alternatives available?” This approach ensures patients are actively involved in making informed decisions about their care.
It is essential to navigate this delicate balance to avoid compromising patient safety through unintended consequences.
Understanding C-Diff
C-diff is a bacterium that causes inflammation of the colon, typically triggered by the use of broad-spectrum antibiotics. These antibiotics disrupt the normal bacterial balance in the colon, disproportionately eliminating “good” bacteria.
This disruption allows C-diff to thrive in immunocompromised patients who already have reduced levels of protective flora. The bacteria produce toxins, leading to symptoms ranging from diarrhea that diminishes the quality of life to life-threatening colitis. C-diff is notoriously difficult to eradicate and frequently recurs, posing a persistent threat.
For immunocompromised patients, the stakes are even higher; a study in an intensive care setting showed a 90-day mortality rate of 56% for such patients, underscoring the critical need for vigilant management and targeted treatment strategies. [1]
Risk Mitigation Strategies
Careful antibiotic stewardship is crucial for patients with a history of C-diff. Stewardship practices include selecting the most appropriate antibiotic based on targeted diagnostics, adjusting the dosage and duration to minimize exposure while effectively treating the infection, and regularly reviewing the antibiotic regimen in response to patient progress and lab results. These measures help prevent the overuse and misuse of antibiotics, which is critical to controlling C-diff recurrence and reducing treatment resistance.
Use Targeting Antibiotics
Stewardship practices start by pinpointing the exact bacteria responsible through targeted diagnostic tests, such as cultures and sensitivity testing, and prescribing an antibiotic targeting the identified pathogen. This maximizes treatment efficacy while minimizing unnecessary exposure to broad-spectrum antibiotics and decreasing the likelihood of extensively disturbing the gut microbiome. This precision in treatment helps in quicker recovery and supports antibiotic stewardship efforts.
The American Society of Colon and Rectal Surgeons emphasizes that implementing an evidence-based antibiotic stewardship program can significantly decrease C-diff infection (CDI) rates by promoting appropriate antibiotic use and limiting the duration of treatment. This includes stopping unnecessary antibiotics and switching to lower-risk antibiotics when possible.[2]
Avoid High-Risk Antibiotics
The Infectious Diseases Society of America advises avoiding antibiotics associated with a high risk of CDI, such as fluoroquinolones, clindamycin, and cephalosporins, particularly in patients with a history of CDI or those at high risk.[3]
Adjunctive Therapies
For patients at high risk of recurrent CDI, adjunctive therapies such as bezlotoxumab, a monoclonal antibody against C. difficile toxin B, can be considered to reduce recurrence rates.[4]
Prophylactic Measures
In certain high-risk patients, secondary prophylaxis with oral vancomycin or fidaxomicin during systemic antibiotic treatment may be beneficial to prevent CDI recurrence.[5]
These strategies aim to balance the need for effective infection control while minimizing the risk of CDI, particularly in vulnerable populations with compromised immune systems and significant comorbidities.
Monitoring and early detection play crucial roles in managing potential C-diff cases. Regularly assessing the patient’s response to antibiotics and watching for early signs of C-diff, such as diarrhea and abdominal pain, enables timely intervention. Adjusting or discontinuing antibiotic therapy in response to these signs can prevent a full-blown CDI, improving patient outcomes significantly.
What Patients Need to Know
If you have a medical history that includes C-diff, it is important to know that broad-spectrum antibiotics carry significant risks and to inform your healthcare providers about your history of C-diff.
Below is a list of antibiotics associated with an increased risk of triggering a C-diff infection because of their disruptive effects on the gut microbiome. [6-9]
Cephalosporins (such as Cefdinir and Cefpodoxime)
Fluoroquinolones (such as Ciprofloxacin, Levofloxacin, and Moxifloxacin)
Clindamycin (Cleocin Phosphate and Cleocin Hydrochloride)
Carbapenems (imipenem, meropenem, and ertapenem)
Broad-spectrum Penicillins (such as amoxicillin/clavulanic acid)
These antibiotics can lead to a marked loss of mucosal barrier and immune function, making the gut more susceptible to C-diff colonization and toxin activity.[10] Therefore, it is crucial to minimize the use of these high-risk antibiotics whenever possible.
Discuss Antibiotic Choices
Here are questions you can use in discussing caution with antibiotics with your doctor:
Is this an antibiotic?
Will it put me at undue risk of a C. difficile recurrence?
Can I avoid oral antibiotic therapy?
Are there other treatment options?
Will it compromise my care by delaying antibiotics and seeing if my condition improves?
When antibiotics are necessary, talk to your healthcare providers about possibly using lower-risk antibiotics, such as benzylpenicillin, gentamicin, or trimethoprim, which are less likely to promote CDI.[6]
Complete the Prescribed Course
Follow the prescribed antibiotic regimen fully to avoid incomplete treatment, which can contribute to resistance and recurrence.
Monitor for Symptoms
Be vigilant for symptoms of C-diff recurrence, such as diarrhea, and seek prompt medical attention if they occur.
Be Your Own Advocate
Understanding these risks and strategies can help you better manage your health and reduce the likelihood of CDI recurrence.
Case in Point: UTI to C-diff to PI-IBS
The patient, a 56-year-old woman with Multiple Myeloma in remission after autologous stem cell transplantation, presented with pain during urination, frequency of urination, and pressure. No fever, no chills, no blood in the urine, no discoloration of the urine.
A health care provider placed a lab order for urine test and prescribed ciprofloxacin 250 Mg once daily for four days. The patient had a history of C-diff; however, the risks of broad-spectrum antibiotics triggering C-diff infections were not discussed.
On day four, the patient still had symptoms. The Ciprofloxacin prescription was increased to 500 Mg twice daily for five days. Subsequent lab reports indicated a moderate amount of Gram-negative rod-shaped bacteria in the urine and a high concentration of E. coli bacteria. The patient was instructed to complete antibiotic treatment, and the symptoms resolved by the end of the treatment.
Five days after completing the antibiotic course, the patient had a diarrhea episode while traveling. Assuming she had eaten something that disagreed with her system, the patient took loperamide (Immodium) to reduce diarrhea during travels. The patient was unaware that the diarrhea could be symptomatic of a CDI, particularly in conjunction with the recent full-spectrum antibiotic treatment.
Diarrhea was intermittent for several days, so the patient notified her care team. The patient was scheduled for a routine follow-up colonoscopy and was advised to call the care team if the diarrhea returned following the colonoscopy.
Diarrhea did return and was now ten or more occurrences daily. A stool sample was obtained, and the patient tested positive for C-diff. The patient was prescribed a course of Vancomycin. After four days without symptom relief, the patient was switched to Metronidazole and given an infusion of Bezlotoxumab. The patient tested negative for C-diff on day 12 of treatment; however, there was no change in symptoms.
The patient was referred to the Infectious Disease (ID) department. The ID doctor could not offer treatment since the UTI and C-diff were resolved. However, she did instruct the patient to avoid broad-spectrum antibiotics if possible. She also suggested that Nitrofurantoin would be a good option if the patient experienced another UTI, and her provider would prescribe an antibiotic.
The diarrhea symptoms continued, and the patient consulted with a gastroenterologist, who diagnosed Post-Infectious Irritable Bowel Syndrome (PI-IBS). Twelve weeks after the initial onset of diarrhea, the patient had a Fecal Microbiota Transplant (FMT) to promote the restoration of the patient’s microbiota and to reduce the risk of recurrence of C-diff.
Summary: Use Broad-Spectrum Antibiotics Prudently in Those with a History of C Diff
Many articles clearly outline how broad-spectrum antibiotics disrupt gut microbiota and significantly increase the risk of C diff infection.
The real issue isn't the lack of information but the need to integrate this knowledge into clinical practice. Greater awareness and education regarding the impacts of antibiotic use and effective antibiotic stewardship are needed.
With infection being such a significant issue and with the high potential for life-threatening consequences for immunocompromised patients with a history of C diff, there is a chilling reality akin to the plot twist in "When a Stranger Calls"—sometimes, the threat comes from within, initiated by treatments meant to protect the patient.
By fostering an environment where every prescription is given with a complete understanding of its implications, we can safeguard against such overlooked risks and ensure that treatments do not inadvertently become threats.
Patients must proactively inform healthcare providers of their C diff history and inquire about the necessity and risks of prescribed antibiotics. Healthcare providers, on their part, must practice stringent antibiotic stewardship, opting for targeted treatments and minimizing the use of broad-spectrum antibiotics that disrupt gut microbiomes and increase the risk of C diff recurrence. Monitoring for early signs of infection, using targeted diagnostic tools, and employing prophylactic measures are crucial in mitigating these risks.
Together, patients and healthcare providers can work to manage these risks through informed decision-making and careful monitoring, ultimately ensuring safer treatment outcomes. Collaboration and vigilance between healthcare providers and patients are essential to manage broad-spectrum antibiotics and protect patients from potential severe complications associated with C diff.
1. Clostridioides Difficile Infections in the Intensive Care Unit: A Monocentric Cohort Study.
Aguilar RC, Salmanton-García J, Carney J, et al.
Infection. 2020;48(3):421-427. doi:10.1007/s15010-020-01413-8.
2. The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Management of Clostridioides Difficile Infection.
Poylin V, Hawkins AT, Bhama AR, et al.
Diseases of the Colon and Rectum. 2021;64(6):650-668. doi:10.1097/DCR.0000000000002047.
3. Strategies to Prevent Clostridioides Difficile Infections in Acute-Care Hospitals: 2022 Update.
Kociolek LK, Gerding DN, Carrico R, et al.
Infection Control and Hospital Epidemiology. 2023;44(4):527-549. doi:10.1017/ice.2023.18.
4. How Can Patients With Clostridioides Difficile Infection on Concomitant Antibiotic Treatment Be Best Managed?
Fitzpatrick F, Safdar N, van Prehn J, Tschudin-Sutter S.
The Lancet. Infectious Diseases. 2022;22(11):e336-e340. doi:10.1016/S1473-3099(22)00274-2.
5. Prevention of Clostridium Difficile Infection in Critically Ill Adults.
Leedahl DD, Personett HA, Nagpal A, Barreto EF.
Pharmacotherapy. 2019;39(3):399-407. doi:10.1002/phar.2200.
6. The Role of Antimicrobial Agents in the Aetiology of Clostridium Difficile-Associated Disease.
Spencer RC.
The Journal of Antimicrobial Chemotherapy. 1998;41 Suppl C:21-7. doi:10.1093/jac/41.suppl_3.21.
7. Critical Care Management of the Patient With Clostridioides Difficile.
Adelman MW, Woodworth MH, Shaffer VO, Martin GS, Kraft CS.
Critical Care Medicine. 2021;49(1):127-139. doi:10.1097/CCM.0000000000004739.
8. Antibiotic Exposure and Risk for Hospital-Associated Clostridioides Difficile Infection.
Webb BJ, Subramanian A, Lopansri B, et al.
Antimicrobial Agents and Chemotherapy. 2020;64(4):e02169-19. doi:10.1128/AAC.02169-19.
9. Common Questions About Clostridium Difficile Infection.
Winslow BT, Onysko M, Thompson KA, Caldwell K, Ehlers GH.
American Family Physician. 2014;89(6):437-42.
10. Clostridioides Difficile-Associated Antibiotics Alter Human Mucosal Barrier Functions by Microbiome-Independent Mechanisms.
Kester JC, Brubaker DK, Velazquez J, et al.
Antimicrobial Agents and Chemotherapy. 2020;64(4):e01404-19. doi:10.1128/AAC.01404-19.
This is such a well-written, thoroughly researched article…and in your case “experienced.” The medical community owes you a depth of gratitude.
Thank you for such an in-depth explanation. It's important for people with multiple myeloma to have an understanding of the options, and that those options are changing.