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Antibiotic that can cause c diff: C. difficile infection – Symptoms and causes

by alexxlab

Antibiotics that cause C.Diff (and which ones probably don’t)

The introduction of antibiotics to cure infections undoubtedly revolutionized medicine over the past century. But some of these “wonder drugs,” as they were once called, can also leave the body vulnerable to an infectious disease called C.Difficile. 

What is C.Diff?

Clostridioides difficile, formerly known as Clostridium difficile, or C.Diff, is a contagious bacteria that can cause severe diarrhea. Other common C.Diff symptoms include fever, nausea, loss of appetite, and abdominal pain.

It’s estimated to cause almost 500,000 illnesses in the United States and 15,000 deaths each year, according to the Centers for Disease Control and Prevention. It is currently classified by the CDC as an “Urgent Threat”—the Centers’ highest threat level—to human health from an infectious pathogen in the U.S. (The CDC plans to release an updated report regarding this data in fall 2019.) 

Which antibiotics cause C. Diff?

So how exactly does antibiotic usage make one susceptible to a life-threatening disease like C.Diff? When you take an antibiotic, it works to kill a bacterial infection in your body. In the process, these drugs can also destroy the healthy bacteria that keep invaders like C.Diff in check. It’s important to note, not all antibiotics cause C.Diff, and not everyone has the same risk. Although almost any antibiotic can cause it, the worst culprit, in this case, is often broad-spectrum antibiotics. Those most at risk are patients 65 or older who have been in a healthcare setting, such as a hospital or nursing home. 

“Broad-spectrum antibiotics have activity against a [large] range of bacteria that reside in the gut,” explains Dr. Hana Akselrod, assistant professor of medicine in the Division of Infectious Disease at the George Washington School of Medicine and Health Sciences. “It’s very important to have a healthy and diverse population of these bacteria.” When people are given broad-spectrum antibiotics, “their gut bacteria are depleted,” thereby allowing for a “pathogenic species,” such as C. Diff, to “essentially create overgrowth of aggressive bacteria that produce toxins that damage the bowel and create very severe illness.”

Erika Prouty, Pharm.D., former adjunct professor at Western New England University College of Pharmacy in Springfield, Massachusetts, breaks it down further: Broad-spectrum antibiotics can be potentially threatening for patients because they “not only target the bad bacteria we’re trying to eradicate, but they also kill a lot of the good bacteria that’s in our digestive system.” 

Both Dr. Akselrod and Dr. Prouty identify clindamycin and fluoroquinolones as some of the worst offenders. The list of antibiotics that could cause C.Diff includes:

  • cephalosporins
  • clindamycin (Cleocin)
  • ciprofloxacin (Cipro)
  • levofloxacin (Levaquin)
  • moxifloxacin (Avalox, Vigamox)
  • amoxicillin (Amoxil)

“It’s unfortunate,” says Dr. Akselrod, “because those antibiotics are in wide use for everything from pneumonia to urinary tract infections. ” The other issue is the necessity of certain IV antibiotics regularly used by physicians in hospital emergency rooms, which also fall under the “broad-spectrum” umbrella. These drugs include:

  • piperacillin/tazobactam (Zosyn)
  • meropenem (Merrem)

IV antibiotics are routine in an ER setting because they’re used as a “first-line therapy when patients come in sick and they’re not sure what’s causing the infection,” explains Dr. Akselrod. But as a medical professional immersed in this field, she is well-aware of the fine line physicians must walk in terms of both treating the illness at hand, while not introducing additional infection. “Over time we’ve become cognizant of the risks versus the benefits of this kind of broad-standard therapy,” she says. “It can be a tough call whether or not to start IV antibiotics. What helps us make the right decision is a judicious approach and trying to have a specific reason for giving antibiotics.”

Which antibiotics are less likely to cause C. Diff?

If you are at high risk for C.Diff, it’s worth talking to your doctor about choosing a lower-risk treatment. The antibiotics that are less likely to cause C.Diff include:

  • azithromycin (Zithromax, Z-Pak)
  • clarithromycin (Biaxin)
  • doxycycline (Oracea, Vibramycin)
  • erythromycin (Eryped)
  • fidaxomicin (Dificid)
  • minocycline (Minocin, Solodyn)
  • metronidazole (Flagyl)

What antibiotics treat C.Diff?

Although broad-spectrum meds are at the top of the list of C.Diff causes, there are only a few types of C.Diff antibiotics capable of curing this particular infection. Vancomycin is the most frequently used antibiotic for C.Diff, says Dr. Prouty, citing the importance of oral, as opposed to IV, treatment: “The IV doesn’t actually penetrate the gastro-intestinal system, so it’s pretty much useless.” And since all infections are caused by different microbes (a bacterium that causes disease), “not all antibiotics are going to target those microbes and kill them,” she says. Therefore,specific drugs must be used in C.Diff treatment. 

It has been suggested that rates of C.diff have fallen in recent years at least partially due to antibiotic stewardship programs in hospitals, which seek to reduce the prescribing of unnecessary antibiotics. But when it comes to patients being proactive over C.Diff prevention, Dr. Akselrod says the number one thing they can do is have a frank conversation with their medical provider about whether or not they “really need that antibiotic, and to minimize the time spent on it.” 

Which Antibiotics Are Most Associated with Causing Clostridium difficile Diarrhea?

All antibiotics are thought to increase the risk of Clostridium difficile diarrhea, but current evidence suggests that particular drug classes are much worse than others in increasing this risk

Clostridium difficile (C difficile) is responsible for 20-30% of antibiotic-associated diarrhea cases and is the most common cause of infectious diarrhea in the healthcare setting. 1 Over the past decade, the overall incidence rate of C difficile has increased, outbreaks of virulent strains have been identified (such as the NAP1/BI/027), and the risk of community-acquired C difficile has become more common.2 Given that any antibiotic may theoretically increase the risk of C difficile infection, are certain antibiotics more associated with this risk than others?

Non-Modifiable Risk Factors for C difficile Infection

The Infectious Diseases Society of America (IDSA) guidelines clearly outline that the most significant risk factor for C difficile infection is older age, particularly in those 65 years of age and older.1 In addition, hospitalization and duration of hospitalization are also 2 significant risk factors for C difficile infection. While it is important to recognize that age and hospitalization are risk factors, these cannot be modified to reduce a patient’s risk of infection.

Antibiotics: the Most Important Modifiable Risk Factors for Infection

Nearly any antibiotic is capable of disrupting the normal gut microflora, which can allow for C difficile to flourish and produce toxin.1 Surprisingly, even single doses of antibiotics for surgical prophylaxis have been associated with an increased risk of C difficile infection. In general, a longer antibiotic duration and multiple antibiotics (versus a single antibiotic) are 2 risk factors that increase the risk of antibiotic-associated C difficile diarrhea. Aside from these 2 standard antimicrobial stewardship principles, the IDSA guidelines are relatively silent regarding specific antibiotic drugs or drug classes that may carry a higher risk of C difficile infection.

Multiple studies have been conducted to assess the comparative risk of different antibiotics for C difficile infection.3-5 Although there is heterogeneity in the studies available, multiple meta-analyses have concluded similar findings regarding which antibiotic classes are at the highest risk for C difficile infection.

Antibiotic Classes with Highest Risk of C difficile (odds ratio 5 or more)

Without a doubt, clindamycin carries the highest risk of C difficile infection with an odds ratio of about 17-20 compared to no antibiotic exposure.3-5 Fluoroquinolones, cephalosporins, aztreonam, and carbapenems carry a fairly high risk, all of which being associated with an odds ratio of approximately 5 compared to no antibiotic exposure.

Antibiotic Classes with Moderate Risk of C difficile (odds ratio 1 to 5)

Macrolides, sulfonamides/trimethoprim, and penicillins are associated with a moderate risk of C difficile infection with odds ratios between about 1.8 and 3.3.3-5 Within this group, penicillins are generally associated with a slightly higher risk (odds ratio about 50% higher) compared to macrolides and sulfonamides/trimethoprim.

Clinical Implications of C difficile Risk Data

On the basis of the available data, clindamycin should absolutely be avoided among patients who are at risk for C difficile infection, particularly in elderly patients and those with frequent antibiotic exposure or hospitalizations. Given the available data, it’s clear that clindamycin is a well-deserving candidate of its boxed warning specifically for C difficile risk.6

For community-acquired pneumonia, it has been suggested that a tetracycline may be substituted in place of azithromycin (or another macrolide) among elderly patients at higher risk for C difficile infection.7 In fact, data suggests that tetracyclines may NOT increased risk of C difficile infection at all, with a non-significant odd ratio of 0.9 versus no antibiotic exposure.3,4

In patients hospitalized with severe infections who require anti-Pseudomonal coverage, the available data suggests that penicillins (such as piperacillin/tazobactam) may have a lower risk of C difficile infection versus cephalosporins (such as cefepime) or carbapenems (such as meropenem). While this risk is certainly relevant to the selection of antimicrobials, local resistance patterns should also be considered when selecting an agent.

Knowledge of high-risk and lower-risk antibiotics for C difficile infection is important, particularly in patients who are already at a higher risk for C difficile infection, such as elderly patients. Avoidance of these high-risk antibiotics when other first-line alternatives exist in certain patient populations should be an antimicrobial stewardship intervention for pharmacists to reduce the risk of C difficile infection both in the inpatient and outpatient settings.

References

  • Cohen SH, Gerding DN, Johnson S, et al. Clinical Practice Guidelines for Clostridium difficile Infection in Adults: 2010 Update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA). Infect Control Hosp Epidemiol. 2010;31(5):431-455. doi:10.1086/651706.
  • Collins CE, Ayturk MD, Flahive JM, Emhoff TA, Anderson FA, Santry HP. Epidemiology and outcomes of community-acquired Clostridium difficile infections in Medicare beneficiaries. J Am Coll Surg. 2014;218(6):1141-1147.e1. doi:10.1016/j.jamcollsurg.2014.01.053.
  • Deshpande A, Pasupuleti V, Thota P, et al. Community-associated Clostridium difficile infection and antibiotics: a meta-analysis. J Antimicrob Chemother. 2013;68(9):1951-1961. doi:10.1093/jac/dkt129.
  • Brown KA, Khanafer N, Daneman N, Fisman DN. Meta-Analysis of Antibiotics and the Risk of Community-Associated Clostridium difficile Infection. Antimicrob Agents Chemother. 2013;57(5):2326-2332. doi:10.1128/AAC.02176-12.
  • Vardakas KZ, Trigkidis KK, Boukouvala E, Falagas ME. Clostridium difficile infection following systemic antibiotic administration in randomised controlled trials: a systematic review and meta-analysis. Int J Antimicrob Agents. 2016;48(1):1-10. doi:10.1016/j.ijantimicag.2016.03.008.
  • Clindamycin [package insert]. Morgantown, WV: Mylan Pharmaceuticals Inc; 2013.
  • Bella SD, Taglietti F, Petrosillo N. Are There Reasons To Prefer Tetracyclines to Macrolides in Older Patients with Community-Acquired Pneumonia? Antimicrobial Agents and Chemother. 2013;57(8):4093. doi:10.1128/AAC.00828-13.

Clostridium difficile. ABC of antibiotic therapy. Vidal medicines guide

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The materials are intended exclusively for doctors and specialists with higher medical education. Articles are informational and educational in nature. Self-medication and self-diagnosis are extremely dangerous for health. The author of the articles does not give medical advice: a clinical pharmacologist is a doctor only and exclusively for doctors.

Author: Trubacheva E.S., clinical pharmacologist

A conversation about clostridium would be incomplete without the most nosocomial representative of them – Clostridium difficile . In addition, now is the most suitable occasion to recall it, since all kinds of schemes, including antibiotic therapy, in the treatment of viral pneumonia caused by SARS-CoV-2 in repurposed hospitals could further train the nosocomial microflora, which includes the aforementioned clostridium.

Toxigenic strains C. difficile are currently regarded as unambiguous causative agents of nosocomial infections. That is, the pseudomembranous colitis they cause is a disease associated with the provision of medical care, that is, iatrogenic. And we all know how the Investigative Committee treats this and, most importantly, is not going to stop (according to the last interview of the chairman of the Investigative Committee A. Bastrykin). Therefore, it is necessary to go into as much detail as possible about how this disease is caused, what provokes it, and how, if not avoided, then treat it as effectively as possible. This is what the current discussion will be about.

Microbiological aspects

C. difficile , like other clinically significant clostridia, is a strict anaerobe. The main damaging factor for her, as well as for other clostridia, are toxins, and just like other clostridia, C. difficile can form spores. The disease caused by toxigenic C. difficile , is called pseudomembranous colitis.

Now let’s note the particulars:

  1. C. difficile are widely distributed in nature – in natural reservoirs, soil, pools, but they do not have the ability to produce toxins and therefore have no clinical significance.
  2. C. difficile has natural antagonists that can and do suppress its uncontrolled reproduction in the large intestine. Such antagonists include enterococci, lactobacilli, bifidobacteria, non-sporogenous anaerobes and – suddenly – Pseudomonas aeruginosa. As long as this flora is intact, no problem C. difficile will not deliver.
  3. If the antagonists die for any reason or their number decreases sharply, then C. difficile receives a selective advantage and, in addition to rapid reproduction, no less rapid toxin formation begins. Clinically significant toxins C. difficile include enterotoxin A and cytotoxin B, which belong to the family of “big clostridia toxins”. Moreover, it must be borne in mind that toxins work exclusively in pairs, and C. difficile , does not have a full set of them, cannot cause classic pseudomembranous colitis (PMC).
  4. We should also note the phenomenon that concerns newborns and children under one year old. In the intestines of up to 70% of perfectly healthy children, C. difficile , can be found, moreover, they produce toxin A and at the same time do not cause absolutely any clinic, although they sometimes try to hang “sudden death of newborns” on them. But as long as there is no clinic, this phenomenon should be considered as a healthy carrier, especially since by the end of the first year of life the carrier level drops to 9%, and then it becomes the same with the adult population – no more than 3%. Why does the disease not develop? It is believed that this is due to the immaturity of the intestinal receptor apparatus, and he simply “does not see” the toxin, and therefore does not react.

Epidemiological aspects

The main source of toxigenic C. difficile is either a diseased or healthy carrier. The route of distribution is fecal-oral or contact. Since disputes C. difficile safely persist up to 180 days, then some outbreaks can occur without an apparently identifiable source – rather poorly cleaned hospital toilets, as well as old or improperly treated mattresses. In addition, if suddenly an asymptomatic carrier of C. difficile from among the medical staff turned out to be in the department, and the rest are not particularly used to washing their hands, then these same disputes will be spread by every second employee of not the department, but of the entire hospital – on their hands, dressing gowns, smartphones, seating her on tables, railings and keyboards, completely asymptomatic for herself, but with catastrophic consequences for patients.

Why hospitals? Because it is here that the largest number of antibacterial drugs are used, including not always justified, and C. difficile can gain a selective advantage due to a decrease in the number of antagonist bacteria that previously restrained its reproduction and toxin release.

In which departments cases (or even whole outbreaks) of pseudomembranous colitis are most likely to occur?

  • Intensive care units due to maximum use of antibiotic therapy
  • Surgical departments of almost any profile
  • Burn units
  • Oncology departments using chemotherapy drugs

Therefore, if your patient in the recent past ended up for any reason in one of these departments, then you need to keep in mind the risk of possible carriage of toxigenic C. difficile and the development of MVP in case of prescription of antibiotics.

What antibiotics most often provoke an increase in the number of toskigenic C. difficile and the development of pseudomembranous colitis?

  • Clindamycin, third-generation cephalosporins (the most dangerous is ceftriaxone, especially in high doses), fluoroquinolones

    • are at high risk

  • Medium risk reported with narrow spectrum penicillins and cephalosporins (such as ceftazidime), carbapenems, macrolides, co-trimoxazole
  • Low risk metronidazole, tetracyclines, vancomycin, aminoglycosides
  • No risk with sulfonamides, nitrofurantoin and fosfomycin

Simply put, what knocks out the main competitors from the colon C. difficile , then provides high risks of developing MVP. But, in addition to antibiotics, MVP is also provoked by cytostatic drugs, such as, for example, platinum preparations and methotrexate.

Which patients are at risk of becoming infected with toxigenic C. difficile and developing MVP? Most often these are initially severe patients with burns, after operations on the large intestine, patients with renal insufficiency and any patients in intensive care and intensive care units. And for some reason, patients with HIV show statistics similar to the main population – no more and no less.

Based on the foregoing, the main thing in the containment of C. difficile is prevention, the cornerstone of which is epidemiological surveillance. Only the total cleanliness of hands, toilet rooms, both for patients and staff, as well as the strictest compliance with the requirements of SanPin, especially in medical institutions that have already encountered this beast, can prevent new cases. Let me remind you that mortality in pseudomembranous colitis is more than 50%, and with developed toxic megacolon – 100%.

Clinical aspects

The main problem with C. difficile is its diagnosis. On the one hand, everything is simple – there have long been commercial test systems that allow express tests to detect toxins, on the other hand, who, honestly, has ever seen them live? The author has never seen the work in 15 years. Microbiological diagnostics, on the other hand, requires the presence in the laboratory of not only an anaerobic analyzer, but also a specially trained bacteriologist. Where can you get all this luxury? So the practical doctor has to make a diagnosis based on clinical manifestations, not forgetting about differential diagnosis with other possible infectious diseases of the large and small intestines (which we have already written about in earlier articles: see here, here and here). In addition, it is necessary to think about nosocomial intestinal infections, which no one has canceled either (although they have not seen it for a long time).

At the same time, one should also remember about antibiotic-associated diarrhea, which has nothing to do with MVP and C. For example, diarrhea associated with amoxicillin/clavulanate is caused by amoxicillin/clavulanate metabolites stimulating colonic motility, or macrolides acting on motilin receptors and causing exactly the same diarrhea. And when these two drugs are prescribed in combination, as they like to do in outpatient practice, then antibiotic-associated diarrhea will not fly only to the most resistant patients. By the way, if you still do not warn patients about this extremely laxative effect, then start. But, again, by C. difficile this is completely irrelevant. Almost always, outpatient conditions are resolved by replacing the drug with something less aggressive towards the intestines and reviewing concomitant therapy (for example, there may also be NSAIDs that can also provoke diarrhea).

How does diarrhea during infection C. difficile differ from everything else? A clear connection with hospitalization and the start of antibiotics, especially if the patient had been hospitalized in the previously indicated departments a couple of months before falling into our hands. If on the third day after the appointment of, for example, ceftriaxone, such a patient develops diarrhea, an alarm bell should immediately sound. If there is access to express tests – to determine the presence of toxins, if not, then immediately cancel the antibiotic. If antibiotic therapy is still needed, change it to a drug on the safe list. Do not prescribe beta-lactams! None! Before finding out what is happening with the patient. The patient himself at this time (a day, a maximum of two) must be observed very carefully and in no case should any drugs that reduce intestinal motility be prescribed.

If the change of the antibacterial drug did not change anything in the patient’s condition, the number of episodes of diarrhea also increases or a tense colon begins to be palpated, then we can already talk about pseudomembranous colitis, which can be confirmed by endoscopic methods, where the conclusion will indicate the presence of characteristic pseudomembranes on individual areas or throughout the colon, available for inspection.

What and how to treat?

  • Firstly, such a patient needs to be isolated, otherwise he will re-infect everyone around
  • Secondly, it all depends on the severity of symptoms, with mild and moderate we use oral metronidazole (we need to deliver the drug into the intestinal lumen), with severe – vancomycin, and also orally, the main thing is that there is no toxic megacolon, since this case, the patient has a maximum of a day, and the lethal outcome in this condition is one hundred percent

What is the advantage of metronidazole? It does not cause the selection of resistant strains of enterococci (we discussed enterococci here), it is more accessible and many times cheaper than even the cheapest vancomycin. At the same time, due to its uncontrolled use for any case of diarrhea, it has already formed a fairly decent pool of strains C. difficile, resistant to it, therefore, metronidazole should not be prescribed to patients who have already experienced episodes of nosocomial diarrhea, treated by him, since it is not a fact that you will not have a patient with an already transferred episode of MVP who has vegetative C. difficile was knocked out, and the spores of stable forms have just now waited in the wings.

In conclusion, we note that hospitals that were “covidaria” have now begun to return to service, in which everything was used, and after long months of being in special protection, employees can sharply relax in order to comply with sanitary and epidemiological rules, and this is why we and reminded about C.difficile , which, like a time bomb, can explode where it was not expected at all. Therefore, it is better not to relax.

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  • Subsection introduction

Clostridium difficile infection

Clostridium difficile, or C. difficile, a bacterium that infects the colon (colon) and causes diarrhea

Spread of C. difficile infection 9 0026

Clostridium difficile occurs in stool and is transmitted by accident contact of people with objects contaminated with feces. This is common in hospitals. Accordingly, the likelihood of infection with C. difficile is higher in hospitalized patients or those who have recently been hospitalized. For this reason C. difficile is called a healthcare-associated infection.

Taking antibiotics (to treat other infections) is one of the main factors that increases the likelihood of C. difficile infection. Antibiotics can kill natural, “good” bacteria in the gastrointestinal tract, giving C. difficile the ability to multiply and start releasing toxic substances. These toxins cause diarrhea and other symptoms of infection.

Older people and people taking acid-reducing drugs for heartburn or acid reflux are more likely to get C. difficile.

Symptoms

Some patients infected with C. difficile have mild symptoms, while others have severe symptoms requiring hospitalization. Such symptoms may include the following

• Diarrhea with watery stools, which in severe cases can lead to dehydration

• Fever

• Abdominal pain and cramps

• Nausea and loss of appetite

Diagnosis and treatment

Infection caused by Clostridium difficile is diagnosed by fecal analysis. In most cases, C. difficile infection is treated with short-term (2 weeks or less) courses of antibiotic tablets. However, some strains of C. difficile are resistant to such antibiotics, and in such cases it is necessary to treat with other antibiotics for a longer period.

Sometimes an infection can be extremely difficult to treat with antibiotics alone. Fecal microbiota transplantation (stool transplantation) is one experimental procedure that has been shown to be effective in some patients with treatment-resistant C. difficile infection. This procedure involves selecting “good” bacteria from a stool sample from a healthy person who does not have a C.