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Antimicrobials during Pregnancy
Published in “Bert” Bertis Britt Little, Drugs and Pregnancy, 2022
Two large studies of sulfonamides during pregnancy have produced different results. In a retrospective case-control study from the US, the frequencies of anencephaly, left side heart defects, coarctation of aorta, transverse limb deficiency, and diaphragmatic hernia were increased among infants born to women who used sulfonamides during the first trimester (Crider et al., 2009). In contrast, no birth defects were increased in frequency among 164 infants born to women who used sulfonamides during the first trimester. An association between sulfonamide exposure during the second trimester and cleft palate was reported (Mølgaard-Nielsen and Hviid, 2012). However, it is unlikely any causal relationship exists, although the authors suggested that an underlying condition may be related to the observed birth defect (cleft palate), but no analysis was done to ascertain whether or not this is the case. Recent analysis of 164 first trimester exposure found no increased risk in birth defects associated with sulfonamide use during organogenesis (Muanda et al., 2017).
Sulfanilamide
Published in Anton C. de Groot, Monographs in Contact Allergy, 2021
Sulfanilamide is a short-acting sulfonamide antibiotic. It is bacteriostatic against most gram-positive and many gram-negative organisms, but many strains of an individual species may be resistant. Sulfanilamide competes with p- aminobenzoic acid (PABA) for the bacterial enzyme dihydropteroate synthase, thereby preventing the incorporation of PABA into dihydrofolic acid, the immediate precursor of folic acid. This leads to an inhibition of bacterial folic acid synthesis and de novo synthesis of purines and pyrimidines, ultimately resulting in cell growth arrest and cell death. Sulfanilamide is used in vaginal cream for the treatment of vulvovaginitis caused by Candida albicans. The active agent sulfanilamide is present in a specially compounded base buffered to the pH (about 4.3) of the normal vagina to encourage the presence of the normally occurring Döderlein’s bacilli in the vagina (1). In Belgium (and probably other countries), it is also available in an ointment for wound treatment.
Anti-Infective Agents
Published in Radhwan Nidal Al-Zidan, Drugs in Pregnancy, 2020
Risk Summary: Taken all together, sulfonamides do not seem to pose a major teratogenic risk. One study has uncovered links with birth defects, but a causative link cannot be determined with this kind of study and they may have been caused by other factors, mainly if trimethoprim was used along with the sulfonamide. Verification is needed. Due to the possible toxicity to the newborn, sulfonamides must be avoided in the 3rd Trimester.
Successful treatment with amoxicillin-clavulanic acid: cutaneous nocardiosis caused by Nocardia brasiliensis
Published in Journal of Dermatological Treatment, 2023
Youqi Ji, Fang Su, Xin Hong, Mengyuan Chen, Yongze Zhu, Dongqing Cheng, Yumei Ge
Trimethoprim-sulfamethoxazole is the first-line antibacterial agent for years in initial therapy of nocardiosis, occasionally combines with amikacin, third-generation cephalosporins, linezolid or imipenem (1,2). However, sulfonamide-resistant or linezolid-resistant Nocardia strains have been isolated in clinical in recent years, which brings great challenges to the clinical treatment of Nocardia (3,4). In addition, Sulfonamides are of great toxicity and side effects (5–8), mainly including: (1) anaphylaxis, accompanied by skin itching, rash, dermatitis or angioneurotic edema; (2) jaundice, abnormal liver function, acute liver necrosis;(3) crystal deposition in the urine, causing hematuria and renal calculus; (4) granulopenia, thrombocytopenia, aplastic anemia; (5) sulfonamides enter the fetal circulation through the placenta and affect infant development. Therefore, non-sulfonamides treatment of nocardiosis should be emphasized. Here, we reported a case of cutaneous nocardiosis caused by Nocardia brasiliensis infection in an immunocompetent individual who was successfully treated with amoxicillin-clavulanic acid.
Dihydrofolate reductase inhibitors: patent landscape and phases of clinical development (2001–2021)
Published in Expert Opinion on Therapeutic Patents, 2022
Kavita Bhagat, Nitish Kumar, Harmandeep Kaur Gulati, Aanchal Sharma, Amandeep Kaur, Jatinder Vir Singh, Harbinder Singh, Preet Mohinder Singh Bedi
Recently in 2019, Hopper et al. published a patent on compounds exhibited higher DHFR inhibitory activity against both T. gondii DHFR (tgDHFR) and human DHFR (hDHFR) as compared to PYR. Pyrimethamine is used with the combination of sulfadiazine for the treatment of Toxoplasmosis caused by Toxoplasma gondii (T. gondii). These drugs showed some drawbacks such as nausea, bone marrow toxicity, leukopenia, teratogenicity, and central nervous system toxicity concerned with PYR while sulfonamides commonly responsible for allergic reactions. It was also found that PYR showed higher selectivity toward T. gondii DHFR (tgDHFR) than human DHFR (hDHFR). To overcome these drawbacks, researchers develop novel pyrimidine derivatives, among them compound 22 (Table 3) came forward from this patent that acts as a dual inhibitor against tgDHF and hDHFR as well as possessed superior inhibitory activity with lesser side effects. This compound 22 has IC50 values of 4.52 and 6.57 µM against hDHFR and tgDHFR respectively, which is considered better than PYR. Additionally, this compound also exhibited significant DHFR inhibitory activity against T. Cruzi DHFR, T. brucei DHFR, L. major DHFR, and P. falciparum DHFR [79].
Contemporary management of the pseudotumor cerebri syndrome
Published in Expert Review of Neurotherapeutics, 2019
A large study showed that patients with a sulfonamide antimicrobial allergy were about 10 times more likely to react to a non-antimicrobial than individuals without a sulfonamide antimicrobial allergy [41]. However, patients with an allergy to penicillin, having a completely different chemical structure, were even more likely to react to a sulfonamide non-antimicrobial (14.2% vs 9.9%) than those patients with a history of sulfonamide antimicrobial allergy [41]. Therefore, a hypersensitivity reaction to a sulfonamide antimicrobial or penicillin may be a non-specific indicator of a predisposition to allergic reactions in general. Drugs that end with ‘sulfate’ or ‘sulfite’ are different than sulfonamides. The likelihood of a patient with a prior allergy to sulfonamide antimicrobials having a life-threatening reaction to either oral (acetazolamide) or topical ophthalmic carbonic anhydrase inhibitors is very low [42].