ESBL Extended-spectrum beta-lactamases HIV Human immunodeciency virus IV Intravenous MRSA Methicillin-resistant Staphylococcus aureus MSSA Methicillin-sensitive Staphylococcus aureus NGS Next-generation sequencing PO Per os

• Colonization of the sinuses, in addition to host risk factors such as immune com-

When considering further antibiotic therapy for persons with recalcitrant chronic rhi­nosinusitis, it is important to consider the reasons for failure of prior antibiotic therapy and whether symptom ares are due to infectious or noninfectious causes. Failure of antimicrobial therapy in an infection may be due to (1) failure to identify the patho­genic organism, (2) pathogen resistance to antimicrobial therapy, (3) anatomic com­plications of infections (e.g., osteomyelitis), (4) inadequate source control, (5) suboptimal antimicrobial bioavailability or dosing, or (6) insufcient duration of therapy. Notably, despite microbial colonization of the sinuses, recalcitrant disease need not be due to infection, rendering any antimicrobial therapy ineffective in symp­tom abatement [5]. The overlap between chronic rhinosinusitis, chronic recalcitrant rhinosinusitis, and chronic infectious rhinosinusitis is shown in Fig.21.1.

Altogether, compromised host defenses, whether due to tissue disruption, immu­nologic factors, or impaired mucociliary clearance, increase the risk of recurrent infections, progression to complicated infection, and repeated antimicrobial therapy exposure, accompanied by sinus colonization with resistant organisms and subse­quent difcult-to-treat infections.

Underlying chronic diseases also impact the microbial composition of the sinus ora. In cystic brosis, the upper airways can be colonized with MRSA, P. aerugi- nosa, or Burkholderia species, which can lead to infection [11]. Patients with poorly controlled diabetes, chronic steroid use, or malignancy not only have frequent, recurrent bacterial infections but are also at risk for more rare invasive fungal dis­eases of the sinuses, similar to patients with hematopoietic stem cell transplants [12]. A high index of suspicion for Mucorales infection is important, as it is

extremely destructive and rapidly progressive, and aggressive treatment can be life­saving. Rarely, atypical mycobacteria [13, 14], Nocardia spp. [15], or even protozoa [16] can be the responsible pathogens and require specialized microbiological pro­cessing and cultures. Concern for infection by these pathogens should prompt con­sultation with infectious disease pharmacists to guide antibiotic selection, given the potential for breeding further resistance.

optimal specimen, method of collection, and specimen transport details are enumer­ated in the Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2018 Update by the Infectious Diseases Society of America and the American Society for Microbiology [19]. Although fresh tissue or uid is necessary for culturing organisms for denitive identication and susceptibility testing, histologic examination of formalin-xed tissues using specialized stains (e.g., Grocott’s Methenamine Silver stain for fungi) can still aid in diagnosis [20].

Due to the variability of host factors and presentation of disease, our belief is that the best approach in treatment includes careful identication of anatomic involve­ment and causative organism by obtaining the results of cultures prior to initiating therapy. If the patient with suspected infection is clinically stable, it is appropriate to defer antimicrobial treatment and to expedite obtaining cultures for true culture­directed therapy.

The severity of illness; the likelihood of infectious complications, e.g., intracra­nial infection; and the presence of impaired host defenses that may predispose patients to rapid clinical progression should be the main considerations in deciding when and whether to start empiric antimicrobial therapy in chronic rhinosinusitis. Empiric antibiotic therapy is necessary in patients who have severe presentations (i.e., symptoms noted in Table21.2) or life-threatening or complicated infections, such as meningoencephalitis, orbital involvement, epidural or subdural empyema, brain abscess, or bacteremia. Notably, individuals meeting at least two of the sys­temic inammatory reaction syndrome criteria (fever >38.0 °C or hypothermia <36.0°C, tachycardia >90 beats/minute, tachypnea >20 breaths/minute, leukocyto­sis >12×109/l, or leukopenia <4×109/l) may have developed sepsis, complicating one of the above infections [31]. When accompanied by hypotension or end-organ system dysfunction, these ndings indicate the presence of septic shock and should prompt urgent initiation of antibiotics; consultation with infectious disease is highly recommended. Host risk factors may lower the threshold for treatment given the potential risk for complications. Special populations such as those with cystic bro­sis, those with primary ciliary dyskinesia, and those who are profoundly immuno­suppressed (e.g., organ transplantation, poorly controlled diabetes, and primary immunodeciency) have an increased risk for severe, extensive infection with risk for progression with secondary complications and catastrophic consequences including hospitalization, transplant organ loss, or death. The prevention of these outcomes is essential.