Trimethoprim synthesis pdf

Bone and joint infections BJIs are a real concern in the context of an increase of orthopedic device implantations in an aging population with comorbidities. In addition to surgery, adequate antimicrobial therapy is required to efficiently treat BJIs [ 1 ].

One drawback with rifampicin is the frequent gastrointestinal side effects and the interaction with the p cytochromes, in particular in polymedicated elderly patients. This makes them particularly attractive due to a broad spectrum of activity with good bone diffusion and the possibility of oral administration [ 2 ].

Moreover, FQs have been shown to be as effective as intravenous beta-lactams for the treatment of osteomyelitis [ 7 , 8 ]. Thus, FQs took a central place in the treatment of BJIs with a high rate of success well-known since the s [ 9 ].

However, in the last decades, resistance to FQs became increasingly prevalent [ 10 ]. Another drawback of FQ therapy is the subsequent risk of Clostridioides difficile infection, in particular in the elderly. Therefore, alternative drugs to FQs are needed. Cotrimoxazole Sulfamethoxazole-Trimethoprim, SXT , is an inhibitor of folinic acid synthesis and has bacteriostatic activity against susceptible bacteria.

Second, its bone diffusion is deemed to be adequate when high posologies are used, including when orally administered [ 17 , 18 ]. Recent studies reported its efficacy especially in association with rifampicin in staphylococcal BJI [ 20 , 21 ], leading to the suggestion of SXT as an alternative to FQs in staphylococcal BJIs in the American, British and French guidelines [ 22 — 24 ]. Despite these encouraging data, SXT use remains limited, partly because of the related risk of adverse events, in particular cutaneous rash and haematotoxicity but also renal and hepatic impairment [ 25 ].

Therefore, new data to evaluate the efficacy and safety of SXT in BJIs are necessary, especially when other recommended oral agents cannot be prescribed. The secondary objective was to assess SXT-related adverse events.

Those 2 teaching hospitals share common staff with weekly pluridisciplinary meetings with an infectious disease specialist, an orthopedic surgeon, a microbiologist and a pharmacist. In our local guidelines, patients undergoing surgery for a BJI were administered empiric broad spectrum intravenous antimicrobial therapy post-operatively combining daptomycin and piperacillin-tazobactam in case of orthopedic device infection ODI , or vancomycin and piperacillin-tazobactam in case of a native BJI, as appropriate.

Those centers managed BJIs during this period. Exclusion criteria were: age under 18 years, being infected by a microorganism non-susceptible to SXT, duration of SXT prescription of less than 10 days prescribed for the drainage of an abscess and a suppressive antimicrobial therapy more than a year of therapy or declining to participate in the study. Descriptive results were expressed using median and interquartile range IQR for the continuous variables when appropriate, and in number with percentage for the categorical variables.

The local Ethics Committee was contacted and there was a waiver of any need for consent, linked to the retrospective nature of this study, since data have already been collected and thereafter data analyzed anonymously.

Overall, patients were screened and are presented in the flow-chart Fig 1. Fifty-one patients were included in the study which represents 3. Population and infection characteristics are detailed in Table 1. Microorganisms are detailed in Table 2.

Overall, 25 patients had organisms which were resistant to fluoroquinolones and 5 patients were considered intolerant to the oral agents, notably among elderly patients related to confusional states. All patients underwent surgery during the course of therapy. The median duration of follow-up was days IQR 99— ; 5 9. Of note, No patient died nor was admitted to intensive care unit in the course of treatment.

Adverse events consisted of a mild hepatitis values up to 3 times above the normal , a short duration watery diarrhea, a cutaneous maculopapular skin rash and an isolated fever in 1 case each. No renal failure was diagnosed during follow-up.

Three of them were lost to follow-up at D We observed a favorable outcome at D90 in It is noteworthy that when used in dual therapy, the second agent combined with SXT did not impact the overall success rate. This rate is gratifying if we consider the higher proportion than usual of these particular prosthetic joint infections due to polymicrobial and Gram-negative bacteria [ 10 , 26 ].

Moreover it concerns elderly and fragile patients with frequent comorbidities who underwent previous surgeries which failed initial therapy as illustrated in Table 1 and therefore required the expertise of a reference center. Indeed, Fica et al. The invention relates to a synthetic method of a trimethoprim impurity 5- 3-bromine-4, 5- dimethoxy benzyl pyrimidine-2, 4-diamine TMP-F.

The synthetic method has the advantages that the trimethoprim impurity TMP-F is directionally designed and synthesized for the first time, the synthetic route is reasonable, raw materials are cheap and easy to obtain, the operation is simple and practicable, the yield is relatively high, and the purify meets the requirements.

A kind of synthetic method of trimethoprim impurity Technical field. The invention belongs to technical field of pharmaceutical chemistry, relate to the synthetic method of an impurity of trimethoprim. Trimethoprim Trimethoprim, TMP , chemical name is 5-[ 3,4,5-trimethoxyphenyl -methyl]-2,4-pyrimidinediamine TMP-F , is Tetrahydrofolate dehydrogenase DHFR inhibitor of miazines, by affecting DNA, the RNA of microorganism and synthesizing of protein, be commonly used for sterilant or sterilizing synergistic agent, the formulation of listing has tablet and injection liquid at present, is mainly used in ephrosis internal medicine, urinary tract infections.

China was once becoming main country of consumption and the supplier of TMP. In the face of the severe challenge of domestic and international market, improving domestic TMP quality is an important means that improves its competitive power.

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