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Antibiotic-associated diarrhea (AAD) refers to antibiotic-related diarrhea
that occurs after antibiotics are applied.
Of the more than 700 known drugs that cause diarrhea, antibiotics account for 25%.
This article summarizes
the classification, diagnostic criteria, and treatment of AAD.
The incidence of classified
AAD varies depending on 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
according to different conditions.
- Patients with simple diarrhea only show loose stool 2~3 times / day, the duration is short, and there are no symptoms
of poisoning due to diarrhea.
- Patients with colitis have more clinical diarrhea, and may be complicated by enteric opportunistic infections (such as Proteus, non-typhoid Salmonella, Pseudomonas, etc.
), and red and white blood cells
may appear in the stool.
- Patients with pseudomembranous enteritis have severe clinical symptoms, diarrhea 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 patients will have severe abdominal pain, bloating, aggravated diarrhea, hypotension, dehydration, electrolyte imbalance, hypoproteinemia or sepsis, etc.
, and even toxic megacolon and high fever, nausea and vomiting and weakened bowel sounds, gastrointestinal failure, diarrhea may stop at this time, and intestinal perforation
may also occur.
What antibiotics can cause antibiotic-associated diarrhea?
Studies have shown that almost all drugs that fight bacteria, 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, these antibiotics either form high concentrations directly in the intestine after oral administration (such as cefixime, cefaclor), or can be excreted through the liver after intravenous drip, form high concentrations in bile and excrete into the intestinal lumen, thereby having a significant impact
on the structure of the intestinal flora.
Aminoglycosides are less common, and antimicrobials against tuberculosis, fungi, and parasites have not been reported
.
Diagnostic criteria
for clinical diagnosis: Diarrhea after recent use or use of antibiotics, loose or watery stools, or even mucous stools, pus and bloody stools, bloody stools, or patchy or tubular pseudomembranes, 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 the presence of intestinal dysbacteriosis is strong evidence
for clinical diagnosis.
Pathogenic diagnosis: If microbiological examination detects the dominant growing pathogenic bacteria, it can be directly diagnosed as the corresponding pathogenic enteritis, such as Candida albicans enteritis
.
Treatment of AAD is based on discontinuation of
existing antibiotics, symptomatic support, and metronidazole or vancomycin
depending on whether Clostridium difficile is cultured.
1.
Antibiotic therapy
For mild AAD, the most prudent approach is to stop 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 targeted when the etiology is clear
.
Metronidazole is suitable for mild and moderate patients, each time oral 500mg, TID, 10d
.
If you are allergic to metronidazole, drug resistant, the patient is pregnant or the causative bacterium is Staphylococcus aureus, vancomycin 125 mg, qid, 10 days
can be taken orally.
For patients with severe infection and 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, 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 goal of restoring the intestinal flora, but so far, clinical data on the use of probiotics in the treatment of AAD are limited
.
Commonly used probiotics are Saccharomyces boulardi, Lactobacillus rhamnosus, Bifidobacterium and so on
.
However, there are no specific recommended regimens
for specific strains, preparations and dosages.
3.
Fecal microbiota transplantation (FMT)
FMT refers to the colonization of functional flora in the feces of healthy donors to the gastrointestinal tract of patients through enemas, nasal feeding or endoscopic implantation to rebuild the homeostasis of
the patient's intestinal flora.
4.
Symptomatic supportive treatment
to correct water and electrolyte and acid-base imbalance
.
Patients with hypoproteinemia can be transfused with albumin or plasma
.
Intravenous gamma globulin is primarily directed at Clostridium difficile toxin and can be used in severe and recurrent CDAD cases
.
Intestinal mucosal protectors and zinc supplements may be used
.
Opioids and enterostatic agents 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
.
Strict control of the use of antibacterial drugs is the fundamental measure to prevent AAD, it is advisable to choose drugs
that have little or narrow impact on the intestinal flora 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 groups such as immunosuppression, critical illness, structural heart disease, and central venous catheterization
.
References:
1.
Fang Feng.
Prevention and diagnosis 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 Clostridium difficile infection diagnosis group criteria[J] .
Chinese Journal of Epidemiology, 2021, 42(1): 64-67.
4.
SONG Yuanyuan, GONG Xuepeng, 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's Handbook of Ward Rounds (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.
