Considerations for antibiotic prophylaxis in head and neck cancer surgery
Introduction
The incidence of surgical site infections (SSI) in head and neck cancer patients undergoing microvascular free-tissue transfer remains high, despite routine peri/post-operative antibiotic prophylaxis (POABP) [1], [2]. While surgical excision and use of free flaps has become mainstay treatment in complex head and neck cancers, the technical components of surgery (e.g. tumor resection, neck dissection, flap harvest and revascularization) contribute to multiple wounds with diverse microbial flora at high risk for SSI [1], [3]. SSI in this setting add to significant patient morbidity and can include flap failure, fistula development, functional or cosmetic abnormalities, and death [4], [5]. SSI also contribute to elevated healthcare expenditure from prolonged patient hospitalizations, thus potentiating additional complications (e.g. post-operative pneumonia, deep-vein thrombosis) that can delay post-surgical chemo- or radiotherapy [6]. Discrepancies in optimal POABP regimens and wound classifications, in addition to difficult infectious risk assessment, are obstacles in the determination of appropriate antibiotic management and the long-term outcomes of head and neck cancer patients who receive free-tissue transfer.
Ketcham et al. were first to describe decreased SSI when using perioperative chloramphenicol in head and neck cancer patients after extensive surgical reconstruction [7]. Subsequent literature has supported POABP use in head and neck cancer surgery [8], [9], [10], [11], but few sufficiently describe best practices regarding spectrum and duration. The majority of published data are limited by comparisons of heterogeneous or obsolete antibiotic regimens, nonstandard wound or SSI endpoint definitions, and small patient samples. Furthermore, many studies were not designed to determine appropriate antibiotic spectrum or durations, or were performed without present-day advancements in surgical technique. These concerns ultimately make study results difficult to extrapolate to the general population. A summary of studies examining relevant antibiotic prophylaxis comparisons in head and neck cancer patients is described in Table 1.
Additional issues surround the potential for free-tissue wound misclassification and the subsequent impact on antibiotic prophylaxis trends. Surgical infection prophylaxis guideline recommendations fail to account for the complexity of wounds secondary to excising fungating tumors and free-tissue transfer relative to other head and neck surgeries [12], [13], [14], [15]. This may contribute to discordance in national antibiotic prophylaxis prescribing habits, irrespective of guideline recommendations [16]. Further, limited data are available regarding risk factors for SSI with multi-drug resistant organisms, such as methicillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa. This proves difficult for clinicians to guide informed therapeutic decisions and prevent potential antibiotic overexposure, which can ultimately lead to antibiotic resistance and other severe antimicrobial-related adverse effects [17].
This focused review provides updated information regarding evidence-based POABP use in head and neck cancer microvascular reconstruction. This includes SSI microbiology, POABP selection, dosing, and duration considerations, and challenges presented in the context of antimicrobial stewardship.
Section snippets
Literature search strategy
The following Medical Subject Headings terms were used to identify literature associated with this topic: “antibiotic prophylaxis”, “head and neck neoplasms”, “head and neck cancer”, “cancer of head and neck”, “cancer of the head and neck”, “free tissue flaps”, “free flap, microsurgical”. Subsequent broad key terms were searched using the PubMed database: “antibiotic prophylaxis head neck cancer”, “antimicrobial prophylaxis head neck cancer surgery”, “antibiotic prophylaxis free flap”. Other
Epidemiology of surgical site infections
Surgical site infections are the most common complication after extensive surgical resection of the head and neck, and occur in 13–51% of cases [2], [19], [20], [21], [22], [23]. SSI are formally defined as infections of the incision, organ, or space that occur after a surgical procedure [12]. While risk factors for SSI have been previously described [2], [4], [19], [24], [25], [26], the amount of inter-patient variability and disease severity complicates the approach of reliably predicting
Surgical site infection reporting and wound classification
Reporting standardized metrics is necessary to longitudinally track outcomes, provide quality assurance, and continually improve patient care. A common surgical metric of morbidity is SSI [30], [31]. SSI surveillance reporting is required in United States acute care hospitals [12], [32], [33] and is performed in accordance with the American College of Surgeons National Surgical Quality Improvement Program reporting standards (ACS NSQIP) and the Centers for Disease Control and Prevention’s (CDC)
Microbiology of the head and neck
The microbiome of the head and neck involves Gram-positive and facultative anaerobic bacteria that normally colonize the aero-digestive tract [37]. While not typically considered colonizers of the head and neck in healthy persons, the flora of head and neck cancer patients can also contain Enterobacteriaceae and other Gram-negative organisms [38]. Clinicians must also account for the introduction of different microorganisms from harvested flap tissue that contribute to the diverse bacteria
Spectrum of activity
Utilizing antibiotic prophylaxis with a spectrum targeted towards the organisms most likely to cause infection can prevent unnecessary patient harm. As the availability of specific antimicrobials varies based on institutional formulary restrictions, a more pragmatic approach is to quantify POABP by meaningful spectrum of activity. While POABP coverage for common Streptococcus and Staphylococcus spp. should be universal due to colonization of these organisms on human skin, the need for
Duration of POABP
National POABP duration prescribing practices vary significantly [16], irrespective of current surgical prophylaxis guideline recommendations for peri-operative antibiotic prophylaxis only [12], [13], [14]. Given the great variation in duration prescribing practices, POABP durations can be conveniently dichotomized to short (e.g. 24 h to 3 days), or prolonged (e.g. 4 to greater than 7 days) [2], [36], [52], [60].
Johnson et al. performed a randomized trial of one or five days of cefoperazone POABP
Antimicrobial stewardship and infection control considerations
Strategies to prevent antimicrobial misuse, a key component of antimicrobial stewardship, include using an appropriate antimicrobial spectrum, dosage, and duration needed to prevent or treat infection. Unnecessary antimicrobial use has contributed to significant antimicrobial resistance and subsequently, extremely limited therapeutic options to treat these infections. Antimicrobial stewardship programs (ASPs) are multidisciplinary organizations that utilize evidence-based recommendations to
Conclusions
Important considerations for appropriate POABP should be taken to decrease the incidence of SSI while minimizing the risks associated with antibiotic exposure. While the existing data is limited, the majority of evidence suggests the need to be cognizant of antibiotic selection, dose, and duration to ultimately improve patient outcomes and prevent significant patient morbidity. Based on existing evidence, short durations (e.g. less than 3 days) of broad-spectrum antibiotics that cover
Acknowledgements
None.
Author contributions
MPV, SLD, AMW, JEM, TAG: Contributions to manuscript draft and critical review.
Disclosures
Competing interests: The authors declare no competing interests.
Sponsorship: None.
Funding source: None.
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