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The Quantiferon-Cytomegalovirus (QF-CMV) assay was introduced to predict CMV infection and inform prophylaxis duration in our lung transplant recipients (LTR) from 2012. The aims of this retrospective cohort study were to review our QF-CMV experience, understand factors associated with positive results and further explore its predictive utility.LTR with QF-CMV testing performed at 5 months post-transplant were included. Patients receiving QF-directed prophylaxis (5 or 11 months) were compared to those receiving our prior standard of care (5 months). Outcomes were CMV infection1,000 IU/mL in blood and/or bronchoalveolar lavage fluid. Factors associated with positive QF-CMV results were identified. Patients were compared based on serostatus, QF-CMV results and prophylaxis duration.Our cohort included 263 LTR (59 D+/R-, 204 R+). QF-directed prophylaxis was used in 195 of 263 (74%) and was associated with reduced CMV infection (84/195, 43% vs 41/68, 60%, p.001). Patients receiving extended prophylaxis experienced less CMV if negative and/or indeterminate (43% vs 70%, p.01) or positive (10% vs 51%, p.01). Only 5 of 59 (8%) D+/R- patients were QF-CMV positive compared to 155 of 204 (76%) R+ patients (adjusted OR 0.03, 0.01-0.07, p.001). After controlling for prophylaxis duration, only D+/R- serostatus remained independently associated with CMV infection (adjusted HR 4.90, 95% CI 2.68-9.00, p.0001).QF-CMV results were strongly correlated with serostatus, with D+/R- patients unlikely to test positive while receiving prophylaxis. Extended prophylaxis was associated with delayed onset, reduced frequency and severity of CMV infection across all subgroups. After accounting for serostatus, the incremental predictive value of QF-CMV in this cohort was limited.

Purpose Recurrent driveline infections due to biofilm formation in the tissue tunnel are extremely challenging to manage. Efficacy of antimicrobials are greatly hindered by the presence of mature biofilms. TYRXTM Absorbable Antibacterial Mesh (TYRX) has been used as a local anti-infective prophylaxis for patients with cardiac implantable devices. The aim of this study was to assess the potential of TYRX in treating biofilm-related driveline infections using in vitro assays. Methods Reference strains and clinical isolates from patients with driveline infections were used, including Staphylococcus aureus, Staphylococcus epidermidis and Pseudomonas aeruginosa. Susceptibility testing was performed with rifampicin and minocycline (antibiotics impregnated in TYRX), their combination, and other local antibiotics, on bacteria grown as planktonic cells and biofilms in 96-well microplates. Minimum inhibitory concentration (MIC), minimum bactericidal concentration, and the minimum biofilm eradication concentration (MBEC) were determined. An interstitial biofilm assay that mimics the driveline tunnel was used to evaluate the activity of TYRX in killing biofilms on HMIII driveline smooth and velour sections. Results High concentrations (133-2600 x MIC) of local antibiotics were required to kill microplate-based biofilms. Rifampicin outperformed other antibiotics in eradicating staphylococcal biofilms, supported by the lowest MBECs (8-16 mg/L). Rifampicin and minocycline appeared to be synergistic, with a combination at MIC eradicating microplate-grown staphylococcal biofilms. A layer of TYRX in the tunnel for 24 h killed staphylococcal biofilms on smooth drivelines by 2.1-6.8 logs, and that on velour by 1.0-2.3 logs, more effective than local vancomycin at 2560 mg/L (Fig. 1). There was minimal antimicrobial activity of TYRX against P. aeruginosa biofilms. Conclusion TYRX may be useful in treating staphylococcal but not pseudomonal driveline infections.

Purpose Determining the optimal level of immunosuppression in lung transplant (LT) recipients is challenging. The Quantiferon®-Monitor (QFM) is a novel immune function assay that measures interferon-γ after stimulation with ligands for the innate & adaptive immune system. The aim of this prospective cohort study was to assess the relationships between immunosuppression and QFM results, and the clinical utility of QFM as a predictor of infection/rejection in LT. Methods QFM was tested pre & at 2, 6, 12, 24 & 52 weeks post-LT. Standard immunosuppression included tacrolimus , azathioprine , prednisone & basiliximab in patients with limited renal reserve. Patients were assessed over 1yr for rejection & infection. Results 80 LT patients were recruited from 2015-17 (median age 61, 60% male, 86% bilateral LT and 50% received basiliximab). Pre-transplant QFM results were lower in patients receiving glucocorticoids (median 67 IU/mL, IQR 9-244 vs. 314, 67-499, p=0.01) and those testing cytomegalovirus (CMV) seronegative (71, 5-262 vs. 230, 58-499, p=0.01). QFM values decreased significantly post-transplant then progressively increased (Figure). Trough tacrolimus levels & prednisone doses were associated with post-transplant QFM levels (p viremia occurred in 44% (>1000 copies/mL in 15%), respiratory viral infections in 40% & positive BAL bacterial cultures in 64%. 9 patients (11%) experienced rejection, 4 within 30 days post-transplant. 76% were readmitted & 5 died within 1 yr. QFM results at 2 & 6 weeks were not associated with any of these outcomes. Conclusion Our study demonstrated an association between tacrolimus levels, prednisolone dose & QFM results but was underpowered to detect differences in clinical outcomes. CMV serostatus appeared to have an impact on QFM results both pre- & post-transplant.

Purpose Medihoney is routinely applied to the exit site of Ventricular Assist Device (VAD) drivelines in patients in many Australian hospitals to prevent driveline infections. Its effectiveness as a prophylactic measure remains unclear. We performed a comprehensive in vitro study using microbiological assays that closely mimic the in vivo environment of the driveline exit-site to assess the effectiveness of medihoney in preventing biofilm-related driveline infections. Methods Antimicrobial efficacy testing of medihoney was performed against 24 clinically-relevant bacterial and fungal strains grown as planktonic and biofilm cells. The minimum inhibitory concentration (MIC), minimum biofilm inhibitory concentration, minimum eradication concentration of medihoney, and the activity of individual components of medihoney were assessed. A colony biofilm assay and a drip-flow biofilm reactor assay that mimic chronic wounds and the driveline exit site were used to evaluate medihoney activity in inhibiting early adherent organism monolayers and mature biofilms. Results Medihoney demonstrated activity against planktonic organism cells in 5/6 S. aureus strains, 6/6 of S. epidermidis strains, 1/6 of P. aeruginosa strains and 4/6 of Candida strains using a qualitative disk diffusion susceptibility assay and a quantitative broth microdilution assay [MICs, 10% weight/volume (W/V) medihoney concentrations]. Higher concentrations of medihoney (30-50%, W/V) were required to inhibit the growth of biofilm cells. Eradication of biofilms could not be achieved by medihoney, even at the highest concentration studied. The antibiofilm properties of medihoney were multi-faceted, including sugar content, pH, osmolality and the proposed active ingredient, methylglyoxal (MGO). MGO actually played a less important role than other medihoney characteristics. The colony biofilm assay and the drip flow biofilm reactor showed that medihoney was unable to prevent the maturation of biofilms after early organism adherence, and only had a weak activity against established biofilms. Conclusion Our work suggests a suboptimal effectiveness of medihoney in preventing driveline exit site infections due to biofilm development, warranting further clinical trials before its widespread use can be justified.