Search

For many years, the University of Chicago administered sulfamethoxazole-trimethoprim sulfate (SMZ-TMP) oral suspension to select immunocompromised mouse colonies via the drinking water. In 2014, SMZ-TMP oral suspension was placed on back-order and medicated diet with a different sulfonamide, sulfadiazine-trimethoprim (SDZ-TMP) was used as a replacement. Months after this transition, sentinel mice from the same room as one of the remaining immunocompromised colonies on this diet were found dead or appeared sick. Necropsies revealed cardiomegaly, and histology confirmed myocardial fibrosis in the first 4 sentinel mice examined, consistent with cardiomyopathy. Subsequent sequential monitoring of 2 sentinel mice via echocardiography showed their progression toward decreased cardiac function. Investigation of the housing room revealed that the sentinel mice had been accidently placed on SDZ-TMP diet upon entering the colony housing room. This case report describes cardiomyopathy in 6 ICR mice after long term consumption of SDZ-TMP medicated feed.

Septic arthritis (SA) shows improper response to antibacterial therapy. This study evaluates the effect of prophylactic vitamin C administration on the efficiency of sulfadiazine-trimethoprim (SDT) or florfenicol (FF) in broilers with experimental SA. Broilers (210) were randomly allocated into 7 equal groups: I. Negative control (NC) (normal birds). II. Positive control (PC) that rendered arthritic by injection of multi drug resistant S. aureus in tibiotarsal joint at the age of 35 days. III. Vehicle control (injected with sterile medium). IV. Arthritic FF-treated (20 mg/kg/day). V. Arthritic vitamin C+FF-treated (as above+vitamin C at 15g/100L of D.W. from day 25 of age). VI. Arthritic SDT-treated (35 mg/kg/day). VII. Arthritic vitamin C+SDT-treated. Antibacterials started at day 39 of age and lasted for 5 days. Samplings were performed at the age of 44 and 54 days. A long lasting SA with severe fibrinoheterophilic synovitis and reduced body weights developed in PC broilers as compared to NC group (p

Potentiated sulfonamides, such as sulfadiazine-trimethoprim (SDZ-TRIM), are frequently used antimicrobials in both human and veterinary medicine. To optimise their use in relation to the emerging problem of resistance selection, this paper studied the impact of dose and administration route of SDZ-TRIM on the exposure of the gut microbiota to these antimicrobials. An animal experiment was conducted with 36 pigs, divided into six different treatment groups (n = 6). Three different administration routes were outlined: oral (PO) gavage, intramuscular (IM) injection and medicated feed, with 5-day therapy duration. Conventional dosing (30 mg SDZ-TRIM/kg bodyweight [BW]) and half dosing (15 mg SDZ–TRIM/kg BW) was performed for the oral routes in two applications per day. For the IM route, a conventional dose of 15 mg SDZ-TRIM/kg BW or a double dose of 30 mg SDZ–TRIM/kg BW was administered once daily. After daily collection of blood and faeces, the intestinal content of all animals was sampled in different gastrointestinal tract (GIT) segments, and SDZ and TRIM were quantified. Remarkably, SDZ accumulated in distal GIT segments, independently of the administration route. High concentrations (mean ± standard deviation) up to 26.93 ± 8.36 µg/g, 11.15 ± 3.78 µg/g and 19.36 ± 1.86 µg/g after PO gavage, IM administration and medicated feed, respectively, were measured for SDZ. In contrast, TRIM concentrations decreased from proximal to distal segments and were mostly below the limit of quantification (0.025 µg/g). The high oral bioavailability of SDZ indicates gastrointestinal secretion is a substantial elimination route for SDZ.

A number of drugs of miscellaneous class are capable of producing various degrees of renal damage and will be reviewed in this Chapter. Some have been used extensively in the past for the treatment of general infections (sulfonamides), others have had specific indications (pentamidine, dapsone), and others such as quinolones are of more recent application. Many of these, however, have become currently important because of their use in the various complications occurring in patients with acquired immunodeficiency syndrome (AIDS). Table 1 lists drugs commonly used in patients with AIDS that are known to be nephrotoxic, whereas Table 2 lists those that are known not to be toxic to the kidneys.

The pharmacokinetics of a combination of sulfadiazine and trimethoprim has been studied in 16 patients with varying degrees of reduced renal function. In normal renal function, the serum half-life (t1/2) of active sulfadiazine, total sulfadiazine, and trimethoprim were quite close: 7.7, 9.6, and 12.1 hr, respectively. There was a gradual increase in serum t1/2 with reduction in renal function for both active and total sulfadiazine and for trimethoprim. With accurate determinations of endogenous renal clearance, t1/2 estimates may be made from regression curves presented. The relative distribution in the body was unrelated to renal function. It was similar for the two fractions of sulfonamide and higher for trimethoprim. The means were 0.371, 0.176, and 1.104 L/kg, respectively, for active and total sulfadiazine, and trimethoprim.

132 female hospital employees (mean age 32 years) with uncomplicated, bacteriologically verified acute lower urinary tract infection were included in a randomized study. The patients were treated for 3 or 10 days with a sulfadiazine-trimethoprim combination (500 mg + 150 mg) b.i.d. or for 3 or 10 days with pivmecillinam (500 mg) t.i.d. The first follow-up evaluation was performed 3-5 days after the treatment. In both sulfadiazine-trimethoprim groups the cure rate was 97% and in both pivmecillinam groups 80%. This difference was mainly due to the occurrence of pivmecillinam-resistant Staphylococcus saprophyticus strains. 109 patients attended the second follow-up visit about 4 weeks after treatment. The prevalences of reinfections and relapses were 18% in both 3-day regimens and 4-7% in both 10-day regimens. No side-effects were reported in the 3-day sulfadiazine-trimethoprim group, while about 20% in the corresponding 10-day group had side-effects. Side-effects were not common in patients treated with pivmecillinam.

The authors treated acute flare-ups of chronic bronchitis with a combination of sulfadiazine (SDZ) and trimethoprim (TMP) (cotrimazine). They treated thirty patients for a week, with daily dosages of 900 mg SDZ and 300 mg TMP, in an open trial in comparison with ampicillin 2 g daily. The result of treatment (course and duration of the acute episode, fever, cough, dyspnoea, sputum amount and description, chest sounds, ESR, and WBC count), tested by suitable statistical methods, showed that cotrimazine had excellent therapeutic activity and was readily tolerated; over-all results compared closely with those obtained with ampicillin. In their concluding remarks the authors state that in addition to being effective in the morbid condition selected for trial, cotrimazine offers some advantages over similar combinations of TMP and other sulfonamides, both because of the intrinsic physicochemical and pharmacological properties of SDZ and because of its lower dosage in this combination.

In a clinical double-blind study on 198 patients with a urinary tract infection, no differences were found between comparable groups treated with either sulfadiazine (SD) 1,000 MG/trimethoprim (TM) 320 mg or sulfamethoxazole (SM) 1,600 mg/trimethoprim 320 g daily for 2 weeks. The favorable results were obtained according to the bacteriological control in 85 and 79%, respectively. Also the incidence of side effects was the same (22 and 24%, resp.). The number of cases within which the treatment had to be discontinued did not differ percentually, either (6.6 and 8.4%, resp.). Based on the bacteriological sensitivity tests and the clinical trial, the authors conclude that TM can be combined with SD as well as with SM. Pharmacokinetic advantages, like a lower protein-binding and a lesser metabolism, may even make SD more preferable.