Evaluation of treatment with two weeks of doxycycline on macrolide-resistant strains of Mycoplasma genitalium: a retrospective observational study.

BACKGROUND: Increasing macrolide resistance makes treatment of Mycoplasma genitalium infections challenging. The second-line treatment is moxifloxacin, an antibiotic drug best avoided due to the potential of severe side effects and interactions. This study evaluates the effects of treatment with doxycycline 100 mg twice daily for 2 weeks as an alternative to moxifloxacin. METHODS: This retrospective observational study examined the medical records of patients testing positive for macrolide resistant Mycoplasma genitalium from January 1st, 2016 to September 1st, 2019 in Trondheim, Norway. Information regarding symptoms as well as clinical and microbiological cure was collected. RESULTS: 263 infections from 259 patients (161 females/98 males) were examined. 155 (58.9%) had a negative test of cure following treatment. 34.7% of symptomatic patients not achieving microbiological cure experienced symptom relief or clearance. There was no statistical difference between bacterial loads in symptomatic versus asymptomatic patients. The mean difference was 1.6 × 105 copies/ml (95% CI - 1.4 × 105-4.8 × 105, p = 0.30) for women and 1.4 × 106 copies/ml (95% CI -4.0 × 105-3.2 × 106, p = 0.12) for men. CONCLUSIONS: The cure rate of doxycycline in this study is higher than previously reported. This adds support to doxycycline's role in treatment before initiating treatment with less favorable drugs such as moxifloxacin.

Cytotoxicity and effect on wound re-epithelialization after topical administration of tranexamic acid.

Background: Topical administration of tranexamic acid (TXA) reduces bleeding from surgical wounds similarly to intravenous use, but with negligible risk of adverse systemic events. Topical use is expanding, but is off-label. Surgeons lack guidelines regarding safe topical dosages and modes of administration. The effects of topical TXA on skin cells and wound healing are unknown. This study investigated whether topical TXA might be cytotoxic or affect wound re-epithelialization. Methods: Human keratinocytes and fibroblast cell cultures and an ex vivo human skin wound model were subjected to both short (limited) and long (chronic) exposure to various clinically relevant concentrations of TXA to mimic different modalities of topical administration. Cytotoxicity and effects on wound re-epithelialization were evaluated. Results: In cell culture, toxicity from chronic exposure was associated with increasing concentration and exposure time. Limited exposure to TXA did not cause significant cytotoxicity even at high concentrations. Re-epithelialization was completely absent in wounds chronically exposed to TXA concentrations of 25 mg/ml or above, and 50-100 mg/ml induced epidermolysis of normal epithelium, possibly by a non-toxic mechanism. Wound re-epithelialization was slightly delayed, but not impaired, by limited exposure to 100 mg/ml or chronic exposure to 6·25 mg/ml. Conclusion: Although short exposure to even high concentrations of topical TXA seems well tolerated in vitro, prolonged exposure can be cytotoxic and may affect wound re-epithelialization. Surgeons should adjust the TXA concentration to the planned mode of topical administration in clinical practice.

Antecedentes: La administración tópica de ácido tranexámico (tranexamic acid, TXA) reduce la hemorragia de las heridas quirúrgicas de forma equivalente a su uso endovenoso, pero con un riesgo insignificante de eventos adversos sistémicos. El uso tópico se está expandiendo, pero se realiza fuera de indicación. Los cirujanos no disponen de directrices sobre las dosis para uso tópico seguras y las formas de administración. Se desconocen los efectos del TXA tópico sobre las células de la piel y sobre la curación de las heridas. Nos propusimos investigar si el TXA tópico puede ser citotóxico o afectar la reepitelización de la herida. Métodos: Los cultivos de queratinocitos humanos y fibroblastos y un modelo ex vivo humano de herida en la piel se sometieron a una exposición corta (limitada) y larga (crónica) de varias concentraciones clínicamente relevantes de TXA para simular diferentes modalidades de administración tópica. Se evaluaron la citotoxicidad y los efectos sobre la reepitelización de la herida. Resultados: En los cultivos celulares, la toxicidad de la exposición crónica se correlacionó con el incremento de la concentración y el tiempo de exposición. La exposición limitada al TXA no causó toxicidad significativa incluso a elevadas concentraciones. No se observó reepitelización en heridas expuestas de forma crónica a concentraciones de TXA de 25 mg/ml o superiores, y 50­100 mg/ml provocó epidermólisis del epitelio normal, posiblemente por un mecanismo no tóxico. La reepitelización de la herida se retrasó ligeramente, pero no se deterioró por una exposición limitada de 100 mg/ml o exposición crónica de 6,25 mg/ml. Conclusión: Mientras que la exposición corta, incluso hasta concentraciones elevadas, de TXA tópico parecen ser bien toleradas in vitro, la exposición prolongada al TXA tópico puede ser citotóxica y afectar la reepitelización de la herida. Los cirujanos deben ajustar la concentración de TXA al modo previsto de administración tópica en la práctica clínica.

Bacterial Load in Daily Urine Samples of Patients Infected with Mycoplasma genitalium, Mutation Analysis, and Response to Treatment.

Objective. Increasing macrolide resistant strains of Mycoplasma genitalium is a challenge, and to differentiate between treatment failure and reinfection a timely test of cure (TOC) is warranted. The aim of this study was to evaluate the best time for TOC after five days' treatment of Mycoplasma genitalium infection with azithromycin. Methods. Nineteen patients with positive PCR for Mycoplasma genitalium in urine provided urine samples daily for 2 weeks and on days 21, 28, and 35. Samples were tested by a commercial qPCR and by sequencing of the 23S rRNA gene. Results. Eight patients with a wild type of Mycoplasma genitalium responded successfully within four days after treatment initiation. Eleven patients had a mutation in the 23S rRNA gene. These samples exhibited high variations in bacterial load, and some patients tested negative at several time points during the observation period. Conclusions. Day-to-day fluctuations in the mutation samples allow for false negative TOC during the first 5 weeks after start of treatment. Due to increasing macrolide resistance of Mycoplasma genitalium, pretreatment mutation analysis is recommended. When a wild type is verified, TOC performed one week after initiation of treatment is suggested.