The early recognition of acute bacterial skin infections (ABSIs) and their swift and adequate care are the major determinants of success. The features that can hamper or delay surgical and medical management can lead to ‘difficult-to-treat’ ABSIs.

Delayed diagnosis and belated management are the key obstacles to be overcome. Clinicians should be careful about underestimating the severity of ABSIs and overlooking comorbidities, especially immunosuppression. Many conditions can lead to delayed source control, including a misdiagnosis, interhospital transfers, delayed re-exploration, or extensive injuries. Difficult therapeutic issues can occur, including rapidly destructive infections from highly pathogenic microorganisms (Group-A-streptococci, Vibrio spp., Clostridium spp. and Staphylococcus aureus) or inadequate antibiotic therapy resulting from multidrug-resistant bacteria. Impaired pharmacokinetic capacities of antibiotic agents should also be considered as a source of clinical failure due to insufficient antimicrobial activity at the site of infection.

Microbiological samples should be used for guiding antimicrobial therapy. Risk factors for multidrug-resistant bacteria should be considered, including local epidemiology and comorbidities. The optimization of antibiotic therapy should be achieved. Optimized care should be achieved through multidisciplinary management involving professionals with sufficient and appropriate training.