Summary: | (1) Background: Healthcare-associated infections (HAIs) after head and neck free-flap reconstruction are a common postoperative complication. Risk factors for HAIs in this context and their consequences have not been adequately described. (2) Methods: Ongoing prospective multicentre study between 02/2019 and 12/2020. Demographic characteristics and outcomes were analysed, focusing on infections. (3) Results: Forty out of 65 patients (61.54%) suffered HAIs (surgical site infection: 52.18%, nosocomial pneumonia: 23.20%, bloodstream infection: 13% and urinary tract infection: 5.80%). Methicillin-resistant<i> Staphylococcus aureus</i> (MRSA) and resistant <i>Pseudomonas aeruginosa, Klebsiella pneumoniae</i> and <i>Enterobacter cloacae</i> were the most frequently implicated. The significant risk factors for infection were: previous radiotherapy (Odds ratio (OR): 5.42; 95% confidence interval (CI), 1.39–21.10), anaemia (OR: 8.00; 95% CI, 0.96–66.95), salvage surgery (eight out of eight patients), tracheostomy (OR: 2.86; 95% CI, 1.01–8.14), surgery duration (OR: 1.01; 95% CI, 1.00–1.02), microvascular reoperation <72 h (eight/eight) and flap loss (eight/eight). The major surgical complications were: a need to reoperate (OR: 6.89; 95% CI, 1.42–33.51), prolonged hospital admission (OR: 1.16; 95% CI, 1.06–1.27) and delay in the initiation of postoperative radiotherapy (OR: 9.07; 95% CI, 1.72–47.67). The sixth month mortality rate in patients with HAIs was 7.69% vs. 0% in patients without HAIs (<i>p</i> = 0.50). (4) Conclusions: HAIs were common after this type of surgery, many of them caused by resistant microorganisms. Some modifiable risk factors were identified. Infections played a role in cancer prognosis by delaying adjuvant therapy.
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