Herpes simplex virus (HSV) and cytomegalovirus (CMV) are DNA viruses that are common among humans. Severely immunocompromised patients are at increased risk of developing HSV or CMV disease due to a weakened immune system. Antiviral therapy can be challenging because these drugs have a narrow therapeutic window and show significant pharmacokinetic variability. Above that, immunocompromised patients have various comorbidities like impaired renal function and are exposed to polypharmacy. This scoping review discusses the current pharmacokinetic (PK) and pharmacodynamic (PD) knowledge of antiviral drugs for HSV and CMV treatment in immunocompromised patients. HSV and CMV treatment guidelines are discussed, and multiple treatment interventions are proposed: early detection of drug resistance; optimization of dose to target concentration by therapeutic drug monitoring (TDM) of nucleoside analogs; the introduction of new antiviral drugs; alternation between compounds with different toxicity profiles; and combinations of synergistic antiviral drugs. This research will also serve as guidance for future research, which should focus on prospective evaluation of the benefit of each of these interventions in randomized controlled trials.

Background: Antibiotic use prior to biopsy acquisition in people with diabetes and osteomyelitis of the foot (DFO) might influence bacterial yield in cultures or induce bacterial resistance. Obtaining reliable culture results is pivotal to guide antibiotics for conservative treatment of DFO. Methods: We prospectively analysed cultures of ulcer bed and percutaneous bone biopsies of people with DFO and investigated if antibiotics administered prior to (<2 months up to 7 days) biopsy acquisition led to more negative cultures or increased resistance in virulent bacteria. We calculated relative risks (RR) and 95% confidence intervals (CIs). We stratified analyses according to biopsy type (ulcer bed or bone). Results: We analysed bone and ulcer bed biopsies of 64 people, of whom 29 received prior antibiotics, and found that prior antibiotics did not lead to a higher risk of at least one negative culture (RR 1.3, (CI 0.8–2.0), nor did prior treatment increase the risk of a specific type of negative culture (RR for bone cultures 1.15, (CI 0.75–1.7), RR for ulcer bed cultures 0.92 (CI 0.33–2.6)) or both cultures (RR 1.3 (CI 0.35–4.7), and neither did it increase the risk of antibiotic resistance in the combined bacterial results of ulcer bed and bone cultures (RR 0.64, (CI 0.23–1.8)). Conclusions: Antibiotics administered up to 7 days before obtaining biopsies in people with DFO do not influence culture yield regardless of biopsy type, nor are they associated with more antibiotic resistance.

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