Trimethoprim lactate

Recurring infections and increasing resistances continue to complicate treatment of urinary tract infections. To investigate alternative treatment options, trimethoprim loaded micro- (D[4;3] of 1-9 µm) and nanoparticles (Z-Avg of 200-400 nm) were prepared from two types of poly(d,l-lactic-co-glycolic acid) (PLGA) for instillative therapy. While PLGA 503H microparticles could not be loaded with more than 2.6% trimethoprim, PLGA 2300 entrapped 22%. When preparing nanoparticles, both types displayed an even higher drug load of up to 29% using PLGA 2300, while PLGA 503H drug load stagnated at 10%. After eight hours, drug release from microparticles amounted to 55% (503H) and 35% (2300) whereas total drug release occurred after 8 (503H) and 9 days (2300). In case of nanoparticles, trimethoprim was liberated much faster with 60% after 2 h and a complete release after 24 h from both polymers. PLGA 2300 seems to be the better choice for entrapment of trimethoprim in microparticles considering the drug load. Both polymers, however, seem to be viable options for nanoparticles. Due to the higher overall drug load, nanoparticles seem to be advantageous over microparticles for instillative therapy, especially when prepared with PLGA 2300.

Propylene glycol (PG) is used as a solvent in numerous medications, including trimethoprim/sulfamethoxazole (TMP/SMX) and lorazepam, and is metabolized in the liver to lactic acid. Cases of lactic acidosis related to PG toxicity have been described and always involved large doses of benzodiazepines and PG. We present the first case of severe lactic acidosis after a 3-day course of TMP/SMX alone, involving allegedly safe amounts of PG.A 31-year-old female with neurofibromatosis and pilocytic astrocytoma, receiving temozolomide and steroids, was admitted to the intensive care unit for pneumonia and acute respiratory failure requiring intubation. Her initial hemodynamic and acid-base statuses were normal. She was treated with intravenous TMP/SMX for possible Pneumocystis jirovecii pneumonia and was successfully extubated on day 2. On day 3, she developed tachypnea and arterial blood gas analysis revealed a severe metabolic acidosis (pH 7.2, PCO2 19 mm Hg, bicarbonates 8 mEq/L) with anion gap of 25 mEq/L and lactate of 12.1 mmol/L. TMP/SMX was discontinued and the lactate decreased to 2.9 mmol/L within 24 hours while her plasma bicarbonates normalized, without additional intervention. The patient never developed hypotension or severe hypoxia, and her renal and liver functions were normal. No other cause for lactic acidosis was identified and it resolved after TMP/SMX cessation alone, suggesting PG toxicity.Although PG-related lactic acidosis is well recognized after large doses of lorazepam, clinicians should bear in mind that TMP/SMX contains PG as well and should suspect PG toxicity in patients developing unexplained metabolic acidosis while receiving TMP/SMX.

Pneumocystis jirovecii is a ubiquitous fungus, which causes pneumonia in humans. Diagnosis was hampered by the inability to culture the organism, and based on microscopic examination of respiratory samples or clinical presentation. New assays can assist in the diagnosis and even aid with the emergence of resistant infections. Areas covered: This manuscript will provide background information on Pneumocystis pneumonia (PcP). Diagnosis, from radiological to non-microbiological (e.g. Lactate dehydrogenase) and microbiological investigations (Microscopy, PCR, β-D-Glucan) will be discussed. Recommendations on prophylactic and therapeutic management will be covered. Expert commentary: PcP diagnosis using microscopy is far from optimal and false negatives will occur. With an incidence of 1% or less, the pre-test probability of not having PcP is 99% and testing is suited to excluding disease. Microscopy provides a high degree of diagnostic confidence but it is not infallible, and its lower sensitivity limits its application. Newer diagnostics (PCR, β-D-Glucan) can aid management and improve performance when testing less invasive specimens, such as upper respiratory samples or blood, alleviating clinical pressure. Combination testing may allow PcP to be both diagnosed and excluded, and molecular testing can assist in the detection of emerging resistant PcP.