Time to positivity of acute and chronic periprosthetic joint infection cultures

Introduction: A prolonged incubation time is generally recommended for diagnosing periprosthetic joint infections (PJI). However, in literature, no distinction is made between acute and chronic infections. Methods: All patients with a PJI that underwent surgical debridement between November 2015 and February 2019 with or without revision of the prosthesis were retrospectively evaluated. Synovial fluid, 5 intraoperative periprosthetic tissue samples, and the sonicated prosthesis were cultured. Results: Fifty-nine patients were analyzed, including 21 acute PJIs (33 isolates) and 38 chronic PJIs (46 isolates). In acute PJIs, all isolates grew within 5 days, while this took 11 days for chronic PJIs. Sonication fluid showed the shortest time to positivity (78% at day 2) for chronic PJIs, but no difference was observed for acute PJIs compared to tissue cultures. Conclusion: In contrast to cultures from chronic PJIs, acute PJIs do not need a prolonged incubation time and no clear benefit is observed for sonication. (C) 2020 The Authors. Published by Elsevier Inc

Influence of gender on the performance of urine dipstick and automated urinalysis in the diagnosis of urinary tract infections at the emergency department

BACKGROUND: Urinary tract infections (UTIs) are frequently encountered at the Emergency Department (ED). Given the anatomical differences between men and women, we aimed to clarify differences in the diagnostic performance of urinary parameters at the ED. METHODS: A cohort study of adults presenting at the ED with fever and/or clinical suspected UTI. Performance of urine dipstick (UD) and automated urinalysis (UF-1000i) were analysed for the total study population and men and women separately. We focused on 1) UTI diagnosis and 2) positive urine culture (UC, ≥105 CFU/ml) as outcome. RESULTS: In 360 of 917 cases (39.3%) UTI was established (men/women 35.1%/43.6%). Diagnostic accuracy of UD was around 10% lower in women compared to men. Median automated leucocyte and bacterial count were higher in women compared to men. Diagnostic performance by receiver operating analysis was 0.851 for leucocytes (men/women 0.879/0.817) and 0.850 for bacteria (men/women 0.898/0.791). At 90% sensitivity, cut-off values of leucocyte count (men 60/µL, women 43/µL), and bacterial count (men 75/µL, women 139/µL) showed performance differences in favour of men. In both men and women, diagnostic performance using specified cut-off values was not different between normal and non-normal bladder evacuation. UC was positive in 327 cases (men/women 149/178), as with UTI diagnosis, diagnostic values in men outperformed women. CONCLUSIONS: Overall diagnostic accuracy of urinary parameters for diagnosing UTI is higher in men. The described differences in cut-off values for leukocyte and bacterial counts for diagnosing UTI necessitates gender-specific cut-off values, probably reflecting the influence of anatomical and urogenital differences

Carboplatin- and cisplatin-induced potentiation of moderate-dose radiation cytotoxicity in human lung cancer cell lines.

The interaction between moderate-dose radiation and cisplatin or carboplatin was studied in a cisplatin-sensitive (GLC4) and -resistant (GLC4-CDDP) human small-cell lung cancer cell line. Cellular toxicity was analysed under oxic conditions with the microculture tetrazolium assay. For the platinum and radiation toxicity with the clinically relevant dose ranges applied, this assay was used to obtain information on cell survival after the treatments. Apart from effects on cell survival effects on DNA were also investigated. Configurational DNA changes could be induced by platinum drugs and thereby these drugs might change the frequency of DNA double-strand breaks (dsbs). DNA fragmentation assayed with the clamped homogeneous electric field (CHEF) technique was used as a measure for dsbs in DNA. The radiosensitising effect of the platinum drugs was expressed as enhancement ratio (ER) calculated directly from survival levels of the initial slope of the curve. The highest ER for cisplatin in GLC4 was 1.39 and in GLC4-CDDP 1.38. These were all at 75% cell survival. Carboplatin showed increased enhancement with prolonged incubation up to 1.21 in GLC4 and was equally effective as cisplatin in GLC4-CDDP. According to isobologram analysis, prolonged incubation with both platinum drugs showed at least additivity with radiation for both cell lines at clinically achievable doses. GLC4-CDDP showed cross-resistance to radiation. The radiosensitising capacity of both lung cancer cell lines was not dependent on their platinum sensitivity. The formation of dsbs in DNA directly after radiation was not influenced by pretreatment of either drug in the sensitive or in the resistant cell line. Drug treatment resulted in decreased DNA extractability in control as well as in irradiated cells. Modest enhancement ratio for radiosensitisation by platinum drugs cannot be explained on the level of dsb formation in DNA in both cell lines. Interaction of radiation with the clinically less toxic carboplatin can be improved by prolonged low-dose carboplatin exposure before irradiation and is as potent as cisplatin in the resistant lung cancer cell line. This suggests an advantage in combining radiation and carboplatin in lung cancer patients

Emerging pan-resistance in <i>Trichosporon </i>species:a case report

BACKGROUND: Trichosporon species are ubiquitously spread and known to be part of the normal human flora of the skin and gastrointestinal tract. Trichosporon spp. normally cause superficial infections. However, in the past decade Trichosporon spp. are emerging as opportunistic agents of invasive fungal infections, particularly in severely immunocompromised patients. Clinical isolates are usually sensitive to triazoles, but strains resistant to multiple triazoles have been reported. CASE PRESENTATION: We report a high-level pan-azole resistant Trichosporon dermatis isolate causing an invasive cholangitis in a patient after liver re-transplantation. This infection occurred despite of fluconazole and low dose amphotericin B prophylaxis, and treatment with combined liposomal amphotericin B and voriconazole failed. CONCLUSION: This case and recent reports in literature show that not only bacteria are evolving towards pan-resistance, but also pathogenic yeasts. Prudent use of antifungals is important to withstand emerging antifungal resistance

Mechanism of hyperthermic potentiation of cisplatin action in cisplatin-sensitive and -resistant tumour cells.

In this study, the mechanism(s) by which heat increases cis-diamminedichloroplatinum (cisplatin, cDDP) sensitivity in cDDP-sensitive and -resistant cell lines of murine as well as human origin were investigated. Heating cells at 43 degrees C during cDDP exposure was found to increase drug accumulation significantly in the cDDP-resistant cell lines but had little effect on drug accumulation in the cDDP-sensitive cell lines. DNA adduct formation, however, was significantly increased in all cell lines studied. Furthermore, ongoing formation of platinum (Pt)-DNA adducts after the end of cDDP treatment was enhanced and/or adduct removal was decreased in heated cells, resulting in relatively more DNA damage remaining at 24 h after the end of cDDP exposure. Correlation plots with survival revealed weak correlations with cellular Pt accumulation (r2 = 0.59) and initial Pt-DNA adduct formation (r2 = 0.64). Strong correlations, however, were found with Pt-DNA adducts at 6 h (r2 = 0.97) and 24 h (r2 = 0.89) after the incubation with the drug. In conclusion, the mechanism by which heat sensitizes cells for cDDP action seems to be the sum of multiple factors, which comprise heat effects on accumulation, adduct formation and adduct processing. This mechanism did not seem to differ between cDDP-sensitive and -resistant cells, emphasizing the potential of hyperthermia to reduce cDDP resistance