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Antibiotic-associated diarrhea (AAD) refers to antibiotic-related diarrhea
that occurs after antibiotics are applied.
Of the more than 700 drugs known to cause diarrhoea, antibiotics account for 25%.
This article summarizes the classification, diagnostic criteria, and treatment of AAD
.
The incidence of classified
AAD varies according to the population and the type of antibiotics, generally 5%~25%.
The clinical manifestations are mainly diarrhea, which can be divided into simple diarrhea, colitis or pseudomembranous enteritis
.
- Patients with simple diarrhea only showed loose stool 2~3 times/day, the duration was short, and there were no symptoms
of poisoning due to diarrhea.
- Patients with colitis have more frequent clinical diarrhea, and may be combined with intestinal opportunistic infections (such as Proteus, Salmonella non-typhi, Pseudomonas, etc.
), and red and white blood cells
may appear in the stool.
- Patients with pseudomembranous enteritis have serious clinical symptoms, diarrhea water samples can reach 10~20 times / day, floating pseudomembranes can be seen in the stool, accompanied by fever, abdominal pain, tenesmus, etc
.
A small number of extremely severe cases will have severe abdominal pain, abdominal distention, diarrhea aggravation, hypotension, dehydration, electrolyte imbalance, hypoproteinemia or sepsis, etc.
, and even toxic megacolon and high fever, nausea and vomiting and weakened bowel sounds, gastrointestinal failure, at this time diarrhea may stop, may also occur intestinal perforation
.
Which antibiotics can cause antibiotic-associated diarrhea?
Studies have shown that almost all antibacterial drugs, with the exception of vancomycin, can cause antibiotic-associated diarrhea
.
In clinical work, lincomycin, clincomycin, azithromycin, broad-spectrum penicillin (especially ampicillin) and second- and third-generation cephalosporins are more common, and these antibiotics either form high concentrations directly in the intestine (such as cefixime, cefaclor) after oral administration, or can be excreted through the liver after intravenous infusion, form high concentrations in bile and be excreted into the intestinal lumen, thus having a significant impact
on the structure of intestinal flora.
Aminoglycoside antibiotics occur less frequently, and antibacterial agents against Mycobacterium tuberculosis, fungi, and parasites have not been reported
.
Diagnostic criteriaClinical
diagnosis: Diarrhea loose or watery stools, or even mucous stools, pus-bloody stools, bloody stools, or flaky or tubular pseudomembranes after recent use or use of antibiotics, excluding other diarrhea with clear causes: (1) various primary infectious diarrhea such as bacterial dysentery, (2) intestinal organic diseases such as inflammatory bowel disease, (3) intestinal functional and allergic diseases, (4) gastrointestinal surgery within 1 year, etc.
, can be clinically diagnosed as AAD
.
Confirmation of dysbacteriosis is strong evidence
for clinical diagnosis.
Pathogenic diagnosis: If microbiological examination detects pathogenic bacteria with dominant growth, it can be directly diagnosed as corresponding pathogenic enteritis, such as Candida albicans enteritis
.
The treatment principle of
AAD is to discontinue existing antibiotics, symptomatic support, and metronidazole or vancomycin
according to whether Clostridium difficile is cultured.
1.
Antibiotic therapy
For mild AAD, the most prudent approach is to discontinue or switch to low-risk antibiotics and correct water and electrolyte abnormalities
.
Treatment of more severe AAD and Clostridium difficile-associated diarrhea (CDAD) should be treated with targeted antibiotics
, provided that the etiology is clear.
Metronidazole is indicated for mild to moderate patients, 500 mg orally each time, TID, 10 days
.
If metronidazole is allergic or resistant, the patient is pregnant or the causative organism is Staphylococcus aureus, vancomycin 125 mg, QID, 10 days
can be taken orally.
For patients with severe infection with complications, oral vancomycin 500 mg QID, intravenous metronidazole 500 mg, TID, vancomycin solution (vancomycin 500 mg plus 0.
9% sodium chloride solution 500 mL) enema, QID
.
In patients with recurrent infection, pulse metronidazole or vancomycin pulse regimens
can be repeated.
2.
Probiotic
intestinal dysbacteriosis is the main pathogenesis of all types of AAD, and restoring normal intestinal flora is the treatment of
the disease.
Theoretically, the use of probiotics can achieve the purpose of restoring the intestinal flora, but to date, clinical data on the use of probiotics for the treatment of AAD are limited
.
Commonly used probiotics include Saccharomyces boulardii, Lactobacillus rhamnosus, Bifidobacteria, etc
.
However, there are no specific recommendations for specific strains, formulations, and
dosages.
3.
Fecal microbiota transplantation (FMT) FMT
refers to the colonization of functional flora in the feces of healthy donors into the gastrointestinal tract of patients through enema, nasal feeding or endoscopic implantation to rebuild the homeostasis
of the patient's intestinal flora.
4.
Symptomatic supportive treatment
corrects water and electrolyte and acid-base balance imbalance
.
Patients with hypoproteinemia can be infused with albumin or plasma
.
Intravenous gamma globulin is primarily targeted against Clostridium difficile toxin and can be used in
severe and recurrent cases of CDAD.
Intestinal mucosal protectors and zinc supplementation
may be used.
Opioids and enteromotility inhibitors for pain control are not recommended.
5.
Other
treatment methods include surgery, monoclonal antibody therapy, traditional Chinese medicine, acupuncture, etc
.
Prevention
of AAD focuses on prevention
.
Strictly grasping the indications for the use of antibacterial drugs is the fundamental measure to prevent AAD, and it is advisable to choose drugs that have little impact on the intestinal flora or narrow spectrum or have a low risk of AAD according to the condition
.
Probiotics play an important role in preventing AAD, but should be used
with caution in high-risk populations such as immunosuppression, critical illness, structural heart disease, and central venous catheterization.
References:
1.
Fang Feng.
Prevention and treatment of antibiotic-associated diarrhea [J] .
Chinese Journal of Pediatrics, 2022, 60(7) : 735-737.
2.
ZHENG Yuejie, WU Qingbin, FANG Feng, et al.
Expert consensus on diagnosis, treatment and prevention of antibiotic-associated diarrhea in children [J] .
Chinese Journal of Practical Pediatrics, 2021, 36(6): 424-430.
3.
WU Yuan, LU Jinxing, YAN Zhongqiang, et al.
Interpretation of Group Standards for Diagnosis of Clostridium difficile infection [J] .
Chinese Journal of Epidemiology, 2021, 42(1): 64-67.
4.
SONG Yuanyuan, GONG Xueqian, Xiao Meng, et al.
Research progress on antibiotic-associated diarrhea[J].
Herald of Medicine, 2019, 38(11):5.
5.
ZHU Yueyong,ZHUANG Zehao,DONG Jing.
Gastroenterologist Ward Rounds Manual (2nd Edition)[M].
Beijing:Chemical Industry Press,2017.
6.
Kelly CR, Fischer M, Allegretti JR, et al.
ACG Clinical Guidelines: Prevention, Diagnosis, and Treatment of Clostridioides difficile Infections[J].
Am J Gastroenterol.
2021 Jun 1; 116(6):1124-1147.
