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21 Intravenous Antimicrobial Therapy
223
Table 21.3
Suspected pathogens
Oral streptococci
Streptococcus pneumoniae
Haemophilus inuenzae
Moraxella catarrhalis
Enterobacterales (if resistance
is not suspected)
Enterobacterales (if resistance
IS suspected, e.g., extendedspectrum beta-lactamase
P. aeruginosa Ciprooxacin 400mg IV
**Mucorales/Zygomycetes Liposomal amphotericin
In the setting of increased severity of disease or highly complicated infections (e.g., intra-orbital
infections, empiric intravenous therapy should be initiated to ensure adequate tissue concentrations
of effective antibiotics. Intravenous antibiotic therapy should target suspected pathogens based on
individual host risk factors, prior cultures, and local antibiograms, which can indicate risk for
resistance. In the presence of invasive fungal disease, an infectious disease specialist should be
consulted to guide dose and duration, in conjunction with prompt surgical management. Patients
with ongoing symptoms indicating infection and pending microbiologic culture data may benet
from the initiation of empiric oral therapy if clinically stable in the outpatient setting. Again, the
selection of empiric therapy should be guided by prior culture data if available, as well as local
antibiograms. Clindamycin is not favored as empiric therapy due to inducible resistance in
S. aureus and potential difculties with tolerability. For critically ill patients, dosing adjustment
should be determined in consultation with pharmacists and infectious disease specialists.
*Renal dosing adjustments needed
**Infectious disease consultation strongly recommended. Oral agents for mucorales/zygomycetes
should not be used for acute, uncontrolled disease prior to surgical intervention.
(continued)
Intravenous therapy
Cefuroxime 750mg IV
q8h*
Ceftriaxone 1g IV q24h
Ampicillin/sulbactam 3g
IV q6h*
Levooxacin 500mg IV
q12h*
Moxioxacin 400mg IV
q24h
Ceftriaxone 1g IV q24h Cefpodoxime 200mg PO q12h
Ertapenem* 1g IV q24h
Meropenem* 1g IV q8h
q8h*
Levooxacin 750mg IV
q12h*
Cefepime 2g IV q8h*
Ceftazidime 2g IV q8h*
Piperacillin/tazobactam
3.375g IV q12h*
Meropenem 1g IV q8h*
Aztreonam 2gm IV q8h*
(if true penicillin/
cephalosporin allergy is
present)
5–10mg/kg IV q24h
Oral therapy
Amoxicillin/clavulanate*
875mg/125mg PO q12h
Cefuroxime 250mg PO q12h
Cefpodoxime 200mg PO q12h*
Levooxacin 500mg PO daily*
Moxioxacin 400mg PO q24h
Trimethoprim/sulfamethoxazole
160mg/800mg PO q12h
Ciprooxacin 500mg PO q12h
Trimethoprim/sulfamethoxazole
160mg/800mg PO q12h*
Ciprooxacin 500mg PO q12h*
Ciprooxacin 750mg PO q12h*
Levooxacin 750mg PO q12h*
Posaconazole
Isavuconazole
224
A. V. Dora and M. B. Goetz
Empiric Oral Antimicrobial Therapy
Whereas empiric intravenous therapy is justiable for persons with severe disease,
culture-directed therapy is strongly preferred in persons with non-severe disease for
whom, when there is an indication for antibiotics, oral antimicrobial therapy is usually appropriate. In the occasional circumstances that warrant empiric oral antimicrobial therapy without waiting for culture and susceptibility results, we recommend
following the choices listed in Table21.3 while taking into consideration prior culture results and historical risk factors as discussed in the previous section on intravenous antibiotic therapy. A synopsis of international guideline recommendations
for oral antibiotics in persons with chronic rhinosinusitis has been recently published [5].
Oral Versus Intravenous Therapy
Antimicrobial therapy, when tailored to the pathogen and anatomic location to
ensure tissue penetration, can be efcacious as either oral or intravenous therapy.
For example, recent studies have shown that oral antimicrobial therapy, when
selected on the basis of oral bioavailability and activity in the infected space, is noninferior to intravenous therapy in the treatment of endocarditis and osteomyelitis
[35, 36]. Thus, while appropriate for uncomplicated cases of infection, oral therapy
is also an important therapeutic option for patients with chronic rhinosinusitis complicated by osteomyelitis and other severe disease manifestations, who have
achieved clinical stability after an initial course of intravenous antibiotics and any
necessary surgical interventions.
Therapeutic Considerations forSpecific Pathogens
Staphylococcus
S. aureus is a commonly found pathogen in chronic rhinosinusitis that may form
biolms and cause recurrent infections [4, 37]. MRSA is a concern, especially in
patients with prior MRSA colonization or infection, repeated prior antimicrobial
use, or nosocomial infections. Active intravenous antimicrobials against MRSA
include vancomycin and daptomycin; decreased activity or resistance to either of
these agents is unusual and, when found, should prompt infectious disease consultation. Methicillin-susceptible S. aureus (MSSA) is best treated with either oxacillin
or a rst-generation cephalosporin such as cefazolin, though oxacillin is superior if
there is concern for intracranial infection.
Coagulase-negative staphylococci, e.g., Staphylococcus epidermidis, are common commensal organisms or “skin contaminants.” Recovery of these organisms
can represent sampling error or colonization. However, heavy growth of coagulasenegative staphylococci in multiple, appropriately obtained cultures may represent
21 Intravenous Antimicrobial Therapy
225
true infection and warrant treatment. Methicillin resistance among different coagulase-negative Staphylococcus spp. has become more prevalent over time, making
vancomycin or daptomycin appropriate treatment choices while awaiting denitive
susceptibility test results [38].
Streptococcus
Streptococcus pneumoniae is a common pathogen in acute bacterial sinusitis and
contributes to acute bacterial exacerbations of chronic rhinosinusitis as well.
Invasive disease is particularly a concern in persons with defects in antibody or
complement production (e.g., common variable hypogammaglobulinemia or complement deciency states), who are at an increased risk of meningitis and bacteremia. Fully vaccinated individuals have good protection against severe infection with
this organism. Resistance to penicillin as well as ceftriaxone is increasing, but in
most parts of the world, it is a concern primarily in intracranial infections [39];
although both vancomycin and linezolid remain active against S. pneumoniae,
infectious disease consultation should be obtained to assure appropriate dosing in
these complex infections.
Streptococcus pyogenes (i.e., group A streptococci) is part of the beta-hemolytic
streptococcus group. It is commonly a cause of pharyngitis, and its presence in the
oral ora can be a risk factor for sinus infection. Though it is reliably sensitive to
penicillin and cephalosporins, when complicated by necrotizing fasciitis or toxic
shock syndrome, the addition of clindamycin to halt toxin production is strongly
recommended.
Although often grouped with viridans streptococci, Streptococcus anginosus and
its similar counterparts, Streptococcus intermedius and Streptococcus constellatus,
are particularly virulent and invasive, with a tendency to metastasize to various
organ systems (typically the brain, lungs, and liver) and form abscesses should it
become a bloodstream infection [40]. The presence of these organisms on culture
should prompt a more thorough evaluation to conrm whether infection is localized
or complicated, as source control will impact treatment. S. anginosus is adequately
treated by penicillins or cephalosporins; most microbiology labs will not perform
susceptibility testing due to the reliability of antibiotic activity.
Other viridans group streptococci bacteria are associated with the oropharynx
and are a common cause of odontogenic infections and can be either commensals or
true pathogens [41]. These are sensitive to penicillins and cephalosporins.
Enterococcus
Although Enterococcus faecalis and E. faecium are rarely the root cause of ares of
chronic rhinosinusitis, they have the potential to result in invasive infection in
immunocompromised hosts. Susceptibility testing is essential for appropriate treatment, as vancomycin resistance is becoming increasingly common, particularly in
226
E. faecium. E. faecalis is more reliably sensitive to ampicillin; in penicillin-allergic
patients, vancomycin, daptomycin, and linezolid are alternative agents. When vancomycin resistance is detected, antimicrobials should be selected based on susceptibility data; generally, daptomycin and linezolid (available in both intravenous and
oral forms) are reliable options. Of note, the susceptibility to daptomycin can be
dose-dependent and may require very high doses (10–12mg/kg) in life-threatening
infections.
A. V. Dora and M. B. Goetz
Enterobacterales
Enterobacterales is a family of enteric organisms that includes Enterobacter spp.,
Citrobacter spp., Klebsiella spp., and Escherichia coli. Although uncommonly seen
in healthy sinus ora, these organisms are more common colonizers in chronic rhinosinusitis and have the propensity to cause infection [42]. Importantly, these
organisms along with Serratia marcescens and Acinetobacter baumannii can
develop inducible resistance by producing extended-spectrum beta-lactamases,
leading to cephalosporin resistance and necessitating treatment with broaderspectrum antibiotics, such as carbapenems [34].
Pseudomonas
P. aeruginosa is a gram-negative organism with diverse drug resistance mechanisms
including inducible resistance gene expression (beta-lactamases), efux pumps, and
altered permeability to antimicrobials [43]. The effectiveness of antibiotic therapy
is further adversely affected by biolm formation particularly in persons with
mucociliary disorders and/or multiple courses of prior antibiotic therapy. Due to the
frequency of resistance, the selection of therapy should be susceptibility-dependent.
Although piperacillin/tazobactam, cefepime, aztreonam, and meropenem can often
be used for P. aeruginosa, more resistant isolates may require consideration of ami-
noglycosides (e.g., tobramycin), colistin, or newer agents, as discussed below.
Other Gram-Negative Organisms
Haemophilus inuenzae and Moraxella catarrhalis are commonly implicated in
acute bacterial rhinosinusitis but can also cause acute exacerbations of chronic rhinosinusitis [42]. Although vaccination has reduced the incidence of H. inuenzae
type B, type A and other nontypeable strains are increasingly causes of invasive
infection [44]. For both H. inuenzae and M. catarrhalis, beta-lactamase presence
(indicating penicillin resistance) is common [45]. Beta-lactam/beta-lactamase
inhibitor combinations such as ampicillin/sulbactam or third-generation cephalosporins can be especially efcacious when susceptibility is unknown.
21 Intravenous Antimicrobial Therapy
Eikenella corrodens is present in the human oral ora and can be a source of
periodontal infections. In cases of odontogenic sources of rhinosinusitis ares, it is
important to consider this organism, as clindamycin resistance is frequently seen
[46]. Eikenella is usually seen in polymicrobial infections; therefore, thirdgeneration cephalosporins such as ceftriaxone and beta-lactam/beta-lactamase
inhibitor combinations (e.g., amoxicillin/clavulanate or ampicillin/sulbactam) can
be helpful here as well, as they are active against oral anaerobes.
227
Anaerobes
The altered microbiota in chronic rhinosinusitis includes diverse anaerobes such as
Prevotella, Porphyromonas, Peptostreptococcus, and Fusobacterium [7]. However,
when recovered on appropriately obtained (i.e., anaerobic) cultures, specic antibiotic therapy is usually not necessary, unless there is abscess formation or tissue
necrosis. Although penicillin, ceftriaxone, and clindamycin are suitable for some
mixed aerobic-anaerobic infections, the addition of metronidazole or the use of a
beta-lactam/beta-lactamase inhibitor combination (such as ampicillin/sulbactam
and piperacillin/tazobactam) or, much less often, a carbapenem (e.g., ertapenem) is
warranted in severe, complex infections. Monotherapy with metronidazole, an agent
which has activity against only anaerobes, is not appropriate, as anaerobes are
invariably part of a polymicrobial infection that requires antimicrobial coverage
beyond the anaerobic spectrum.
Multidrug-Resistant Organisms
The emergence of highly resistant organisms is an increasing societal problem
[47–49]. Some of these phenotypes are still rare, such as vancomycin-resistant
S. aureus; however, others are increasingly more prevalent, such as meropenemresistant Acinetobacter baumannii, Burkholderia cepacia complex (especially in
persons with cystic brosis), and carbapenemase-producing carbapenem-resistant
Enterobacterales (e.g., carbapenem-resistant K. pneumoniae). Recently developed
antibiotics, such as ceftolozane-tazobactam, meropenem-vaborbactam, ceftazidime-avibactam, eravacycline, and cederocol can be lifesaving, but resistance to
these antimicrobials has also occurred. The presence of multidrug-resistant organisms on cultures necessitates infectious disease consultation, as patients with true
infection may require combination therapy for treatment.
Candida andOther Fungal Pathogens
Often, in patients with a history of recent broad-spectrum antibiotics, or those with
specic immunodeciencies, bacterial cultures may yield growth of Candida
228
species, even though Candida is a fungus. In the absence of oral candidiasis (thrush),
or another complication (such as an abscess) where Candida may also be cultured,
it should be regarded as a colonizer or contaminate and not treated unless tissue
invasion is demonstrated by histopathology.
While fungal rhinosinusitis will not be discussed in detail, it is important to recognize when the clinical picture, cultures, or imaging studies indicate the presence
of other fungal organisms, such as Aspergillus and zygomycetes. When mycobacte-
ria are isolated, infectious disease consultation can aid in determining if these results
are contaminant, local infection, allergy-mediated disease, or invasive infection and
if therapy should be initiated.
A. V. Dora and M. B. Goetz
Treatment Duration andOther Complicating Factors
For a bacterial are of chronic rhinosinusitis without complications such as abscess,
osteomyelitis or other disease extending beyond the sinuses, a reasonable treatment
duration is 7–10days, especially if adequate drainage of the sinuses is achieved and
an appropriate clinical response to antibiotics is demonstrated. Complicating factors
such as osteomyelitis, abscess formation, or invasive disease such as bacteremia,
ocular/orbital involvement, or extension to the brain may require further imaging,
surgical debridement, and/or source control prior to determining the antibiotic
course duration. Any concern for possible prolongation of therapy may warrant further discussion with an infectious disease consultant for guidance.
The role of extended antimicrobial therapy duration to decrease inammation by
altering the composition of the sinus microbiota in chronic rhinosinusitis remains to
be fully dened. Macrolides, typically administered orally, are considered to have
an anti-inammatory effect. There may be a role for these antibiotics for this antiinammatory effect rather than for pathogen-directed therapy [5].
Antimicrobial Stewardship
Antimicrobial stewardship is of utmost importance given that antibiotic overuse
drives the emergence of drug-resistant organisms and can greatly limit treatment
choices that require the use of less convenient and/or more toxic antibiotics; in
worst case scenarios, there is no effective therapy. The rst step in stewardship is to
ensure the accuracy of the diagnosis of infection and the identity of the responsible
microorganism(s). Next is the prudent selection of empiric antibiotic therapy to
avoid unnecessarily broad-spectrum therapy. When the pathogen is identied,
prompt de-escalation of broad-spectrum antimicrobial therapy in favor of pathogendirected therapy is strongly recommended. These measures, combined with limiting
the duration of therapy to decrease perturbation of the normal sinus microbiome,
can mitigate the emergence of resistant organisms and the risk of individual treatment side effects (such as eosinophilic pneumonia from daptomycin or
21 Intravenous Antimicrobial Therapy
229
tendinopathy with uoroquinolone usage) or the emergence of Clostridium difcileassociated diarrheal illness [50].
Although long-term therapy is needed in complex cases such as osteomyelitis,
prescribing long-term intravenous antibiotic therapy is fraught with its own complications. Administration of intravenous therapy often requires prolonged hospitalizations, with prolonged length of stay due to either coordination for home health
delivery of antibiotics or due to potential delays in obtaining a peripherally inserted
central catheter for home administration. Peripherally inserted central catheters
carry their own risk of complications such as associated thrombosis, line infection,
or cellulitis. Home intravenous antibiotic administration also requires consideration
of antimicrobial cold storage, patient education and health literacy, coordination of
durable medical equipment, and home health nursing for laboratory monitoring of
drug levels and safety, as well as possible administration of antimicrobial therapy if
the patient or caregivers are unable to do so. Intravenous antibiotics administered at
home should always be monitored by a physician, and ideally a pharmacist and
nursing staff to assist in coordination of care delivery and safety monitoring, as the
potential longer-term complications of home intravenous antibiotics include eosinophilia, acute kidney injury, transaminase elevation, or other medication-specic
complications. When appropriate, oral therapy should be used to avoid many of
these complications.
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231
Topical Corticosteroid Therapy
inRecalcitrant Chronic Rhinosinusitis
DanielR.Romano, DanielP.Lander, andJohnS.Schneider
Key Points
• Glucocorticoids have long been a cornerstone of therapy in the treatment of
chronic rhinosinusitis (CRS), and nasal steroid sprays remain a rst-line treatment in many consensus statements.
• A number of CRS patients will experience continued or recurrent symptoms
despite appropriate surgical management and medical maintenance therapy with
intranasal saline irrigations and simple nasal steroid sprays.
• While short courses of oral steroids may lead to temporary symptom control in
these patients, the numerous side effects of systemic steroids make this an unattractive option for long-term CRS management.
• Alternative delivery mechanisms for topical steroid therapy, including intranasal
steroid irrigations and the exhalation delivery system with uticasone propionate
(EDS-FLU), have demonstrated improved paranasal sinus medication distribution in the treatment of CRS.
• Though local factors, systemic conditions, and/or steroid resistance may contrib-
ute to refractory CRS, studies have shown that improved outcomes are often
possible in these patients with improved topical steroid delivery.
22
D. R. Romano · D. P. Lander · J. S. Schneider (*)
Department of Otolaryngology-Head & Neck Surgery, Washington University School of
Medicine, St. Louis, MO, USA
e-mail: d.r.romano@wustl.edu; daniel.lander@wustl.edu; jsschnei@wustl.edu
© The Author(s), under exclusive license to Springer Nature
Switzerland AG 2025
J. T. Lee et al. (eds.), Advances in Surgical and Medical Interventions for
Recalcitrant Chronic Rhinosinusitis,
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