Bacteriology andAntibiotic Resistancein ChronicRhinosinusitis

R. Peter Manes, MDa, Pete S. Batra, MDb,*

Key Points

� Through understanding of microbiology and drug resistance patterns of chronic rhinosinusitis isa requisite if the facial plastic surgeon contemplates concurrent rhinoplasty with FESS.

� The most common organisms assayed in acute rhinosinusitis include Streptococcus pneumoniae,Moraxella catarrhalis, and Haemophilus influenzae.

� The most common organisms cultured in chronic rhinosinusitis are Staphylococcus aureus, coagulase-negative Staphylococcus, and gram-negative rods.

� S aureus is the most common organism seen on chronic sinusitis; its presence during FESS is associatedwith postop S aureus infection and impaired mucosal healing.

� Pseudomonas aeruginosa is the most commonly cultured gram negative rod and can be a source ofrecalcitrance due to biofilm formation.

� Strenotrophomonas maltophilia is a multidrug resistant gram-negative microbe seen in patients withprevious FESS and prior antimicrobial treatment.

� Judicious usage of antimicrobial therapy is recommended for infectious exacerbations of chronicrhinosinusitis, ideally with endoscopically-guided cultures.

KEYWORDS

� Chronic rhinosinusitis � Bacteria � Microbiology of sinusitis� Antibiotics � Bacterial resistance

DILEMMAS IN CONCURRENT MANAGEMENTOF CHRONIC RHINOSINUSITIS IN THERHINOPLASTY PATIENT

Chronic rhinosinusitis (CRS) ranks among themost common health problems in the UnitedStates.1 The comprehensivemanagement algorithmfor CRS entails a variety of medical therapies, such

Disclosures: P.S.B: consultant (Medtronic, LifeCell), researR.P.M: research grant (MedInvent).a Section of Otolaryngology–Head and Neck Surgery,Medicine, 333 Cedar Street, PO Box 208041, New Havenb Comprehensive Skull Base Program, Department of OTexas Southwestern Medical Center, 5323 Harry Hines Bo* Corresponding author.E-mail address: pete.batra@utsouthwestern.edu

Facial Plast Surg Clin N Am 20 (2012) 87–91doi:10.1016/j.fsc.2011.10.0101064-7406/12/$ – see front matter � 2012 Elsevier Inc. All

as antibiotics, oral and/or nasal steroids, leuko-triene antagonists, and saline irrigations, withfunctional endoscopic sinus surgery (FESS) beingreserved for refractory cases. Current estimatessuggest that the number of sinus surgeries per-formed in the United States approximates250,000 annually.2 In some instances, patientsundergoing FESS may inquire about the possibility

ch grants (ARS, Medtronic, MedInvent, Xoran).

Department of Surgery, Yale University School of, CT 06520, USAtolaryngology–Head and Neck Surgery, University ofulevard, Dallas, TX 75390, USA

rights reserved. facialplastic.theclinics.com

Manes & Batra88

of concurrent reconstructive or cosmetic nasalsurgery.As our society becomes more concerned with

appearance and plastic surgery procedures aremore readily available and accepted, requests tocombine elective aesthetic surgery with medicalprocedures will not be uncommon. Patients mayview this as a means to decrease the numberof operations performed for their overall care.Furthermore, the patient mindset may rationalizethis approach with the thought that the surgeon“will be working on the nose anyway.”Diverging opinions exist on the concept of

concurrent FESS and rhinoplasty.

Arguments Against Concomitant FESS andRhinoplasty

Some experts have advocated against theseconcomitant procedures for several importantreasons.3 Intranasal inflammation and intranasalincisions as a result of rhinoplasty greatly add tothe postoperative discomfort and make anyattempt at effective debridement exceedingly diffi-cult. While the exact role of debridement is con-troversial, most rhinologists hold that timelydebridement starting 1 week after surgery isimperative to decrease the risk of synechiaeformation and to achieve optimally functioningpostoperative sinonasal cavities. Furthermore,nasal manipulation for debridement in the earlypostoperative period may alter the delicate posi-tion of the nasal osteotomies and compromisethe cosmetic and functional outcome. Anotherargument against concurrent rhinoplasty andFESS focuses on the possibility of infection, giventhat FESS often takes place in an infected sino-nasal space. Osteotomies performed during rhino-plasty breach the periosteum, creating a potentialroute for the spread of infection. The use ofsynthetic graft material in rhinoplasty adds anothercomplicating factor to the possible spread ofinfection, though avoidance of graft materialsmay worsen outcomes from rhinoplasty.

Arguments for Concomitant FESS andRhinoplasty

Conversely, others have argued that with appro-priate and aggressive medical management ofCRS, including preoperative, intraoperative, andpostoperative antibiotic treatment, the risk ofpotential spread of infection to the nasal or facialtissues is greatly reduced.4 Moreover, the patientis spared an additional anesthetic and postopera-tive recuperative period, perhaps resulting in costsavings in the long term. However, within thatargument rests an important caveat: to provide

appropriate medical management of CRS, onemust understand both its bacteriology and antibi-otic resistance patterns.

BACTERIOLOGY OF RHINOSINUSITIS

Bacteria likely represent the main underlyingcause of acute rhinosinusitis (ARS), with the mostcommonly identified bacteria being Streptococcuspneumoniae, Moraxella catarrhalis, and Haemo-philus influenzae.5 By contrast, the central patho-physiology of CRS remains elusive to date. Avariety of possible etiologic mechanisms havebeen proposed, including microbes (viruses,bacteria, fungi), allergy, osteitis, biofilm, staphylo-coccal superantigen, and derangements in innateand adaptive immunity. Although the exact roleof bacteria in the disease process remains to befully elucidated, it is likely that bacterial infectionplays an important role in CRS, as either a causa-tive or an exacerbating factor.6

Differences in CRS and ARS Microbiology

Themicrobiology of CRS varies greatly from that ofARS. Nadel and colleagues7 evaluated 507 endo-scopically guided cultures in 265 patients. Thepredominant organisms identified included Staph-ylococcus aureus (31.3%), coagulase-negativeStaphylococcus (SCN) (44.2%), and gram-negative rods (34.3%). A multitude of gram-negative organisms were cultured, with the mostcommon being Pseudomonas aeruginosa, Steno-trophomonas maltophilia, Escherichia coli, andSerratia marcescens. Kingdom and Swain8

analyzed 182 total cultures with 257 isolates in101 patients at the time of sinus surgery. Themicrobiological yield was similar; the mostcommon isolates were SCN (45%), gram-negative rods (25%), andS aureus (24%). Compar-ative analysis between primary and revision sinussurgery cases demonstrated no differences in thebacterial yield or types. Bhattacharyya and Gopal9

have demonstrated that whereas approximatelyhalf of the bacteria cultured in CRS are found inisolation, the rest exhibit polymicrobial growth,with 2 or more bacterial species.

STAPHYLOCOCCUS AUREUS

S aureus is a ubiquitousmicroorganism, occupyingthe nasal vestibule of nearly one-third of the humanpopulation at any given time.S aureus has emergedas an important pathogen in community-acquiredand hospital-acquired infections, resulting insepsis, bacteremia, endocarditis, and soft-tissueinfections. S aureus is commonly assayed incultures performed for CRS.7,8,10,11 Nadel and

Bacteriology and Antibiotic Resistance in CRS 89

colleagues7 and Kingdom and Swain8 reported itspresence in 23.1% and 25%of all cultures, respec-tively. Though the exact role in pathogenesis isa matter of debate, the presence of S aureus infec-tion at the time of sinus surgery has been demon-strated to be a strong predictor of postoperative Saureus infection and impaired mucosal healing.

Biofilms and Other Novel Mechanisms ofPathogenicity

A variety of novel mechanisms of pathogenicityhave also been implicated, including biofilmformation, intracellular residency, and toxin-mediated disease.12 Foreman and colleagues13

characterized bacterial biofilm by fluorescence insitu hybridization in 50 CRS patients. Biofilmswere detected in 36 of 50 patients, with S aureusbeing the most common biofilm forming organism.The capacity to form biofilms may confer the abilityto create a recalcitrant infectious milieu unrespon-sive to conventional antimicrobial therapies.Further, enterotoxins derived from S aureus havebeen implicated in the pathophysiology of nasalpolyps as disease-modifying factors.14

Methicillin-Resistant S aureus in ARS and CRS

An increase in the recovery of methicillin-resistantS aureus (MRSA) has recently been noted inacute and CRS and anterior nares of normal indi-viduals. Brook and colleagues15 comparedMRSA rates in chronic maxillary sinusitis betweentwo time periods. S aureus was found in 15 (15%)of the patients between 2001 and 2003, 4 (27%)of which were MRSA. S aureus was cultured in23 (20%) of the patients between 2004 and2006, with 14 (61%) being MRSA. Indeed,MRSA represents a treatment challenge in thesetting of CRS, given the paucity of optimal treat-ment options.Oral antibiotics thatmaybeeffectiveinclude doxycycline, trimethoprim/sulfamethoxa-zole, and clindamycin. Topical mupirocin irriga-tions may also serve as an important adjunct inthe postoperative CRS patient.16 This scenariosuggests that a high index of suspicion must bemaintained for the presence of MRSA sinusitis;endoscopically guided cultures are imperative inguiding targeted oral and/or topical antimicrobialtherapy.

COAGULASE-NEGATIVE STAPHYLOCOCCUS

The exact role of SCN in CRS remains to beelucidated, as its reported incidence varieswidely.8 It has been posited to be a contaminant,supported by previous work that found SCN inthe middle meatus of 56% of healthy patients

and in only 20% of patients with CRS.17 More-over, the microbe is ubiquitous on human skin,thus contamination may occur readily in theabsence of proper sterile precautions duringculture technique. However, different strains ofSCN may have differing abilities to causedisease.

Recent studies evaluating SCN in indwellingdevices have shown that bacterial pathogenicityis dependent on genes associated with biofilmformation, which are only found in certainstrains.18 The presence of SCN may not indicateinfection, as a specific strain may be necessaryfor such an infection to develop. Nonetheless,endoscopically acquired cultures have consis-tently identified SCN in multiple studies in CRS.Bolger10 found SCN in 17%, Hsu and colleagues11

found SCN in 42%, and Nadel and colleagues7

found SCN in 35% of cultures.10,11

One possible method to ascertain the signifi-cance of SCN culture is based on the quantitativegrowth on culture, along with presence of leukocy-tosis on the Gram stain result. Scant or lightgrowth, especially with paucity of gram-positiverods or white blood cells (WBCs) on Gram stain,likely represents contamination. By contrast,moderate to heavy growth, with a large numberof WBCs on Gram stain, should alert the clinicianof the possibility of a true infection.

PSEUDOMONAS AERUGINOSA

Gram-negative rods are often identified in CRScultures, more commonly in patients who haveundergone endoscopic sinus surgery.7,10,11 How-ever, their role in patients with CRS withoutprevious surgery should also not be underesti-mated. Kingdom and Swain8 found gram-negativerods in 31% of cultures in a group of patients atthe time of primary sinus surgery. Nadel andcolleagues7 found gram-negative rods in 9.5% ofcultures taken from patients without previous sinussurgery. P aeruginosa has long been recognizedas an important pathogen in the upper and lowerairway in patients with cystic fibrosis. It also re-presents a common and problematic organism inCRS. Rates of assay in CRS cultures have been re-ported as between 9% and 16%.7,8 Nadel andcolleagues7 noted that that P aeruginosa wasmost commonly cultured in patients with previousFESS and irrigation usage. P aeruginosa also hasthe capability of biofilm formation, which may inpart contribute to its refractory nature in CRSpatients. Furthermore, thepresenceofPaeruginosabiofilm has been associated with poor evolutionafter FESS.19 Fluoroquinolones are the only orallyadministered antibiotic group with efficacy against

Manes & Batra90

P aeruginosa. Quinolone resistance has becomemore problematic, with limited alternative provenoral antimicrobial therapies for Pseudomonasrhinosinusitis.

STENOTROPHOMONAS MALTOPHILIA

S maltophilia is a multidrug-resistant gram-nega-tive bacillus most often encountered as a nosoco-mial pathogen in immunocompromised andintensive care unit patients. Infection with S malto-philia most frequently involves the respiratorytract, bloodstream, wounds, and genitourinarytract. S maltophilia has also been cultured fromthe paranasal sinuses, often in the setting of priorantimicrobial treatment and sinus surgery. Theexact implication of S maltophilia cultures in theparanasal sinuses is unclear. Whether this repre-sents a true infection by an atypical microorganismor colonization that surfaces after eradication ofother microbes by antimicrobial therapy deservesadditional research. Despite its multidrug-resistant nature, the use of trimethoprim/sulfame-thoxazole and fluoroquinolone monotherapy hasshown improvement of symptoms and endo-scopic findings in CRS patients.20

TRENDS IN BACTERIAL RESISTANCE

Antibiotic therapy is often used as an essentialcomponent of the comprehensive managementstrategy in the initial treatment of CRS and recur-rent acute exacerbations of CRS. However,increased antibiotic exposure results in the poten-tial for antibiotic resistance, which is especiallyproblematic in patients with a chronic diseaseprocess, not infrequently requiring long-termmedical therapy. As such, it is important to under-stand trends in antibiotic resistance in CRS, as thismay have important clinical consequences in theability to manage CRS.Bhattacharyya and Kepnes21 retrospectively re-

viewed a microbiological database to extract allendoscopically obtained cultures in adult patientswith CRS from 2001 to 2005. A total of 701 bacterialisolates were reported. S aureus was the mostcommonly isolated organism (19%). Overall, antibi-otic resistance significantly increased for erythro-mycin throughout the study, with a maximumresistance rate of 69.7%. Resistance remainedunchanged for methicillin, clindamycin, levofloxa-cin, and sulfamethoxazole. Overall, 19% of Saureus species expressed methicillin resistance.MRSA species exhibited statistically significantlyhigher rates of resistance to other antibiotics testedcomparedwith non-MRSAbacteria. The increasingresistance to erythromycin may have been due to

the trend to use macrolide antibiotics for theirimmunomodulatory, as well as antimicrobial,effect. This possibility does not necessarily indi-cate a resistance to macrolides as a class, butindicates poor effectiveness of erythromycin itself.While the rate of methicillin resistance amongall bacteria evaluated (not only S aureus) remainedstable, it still averaged greater than 30%,showing declining efficacy of first-generationcephalosporins.These results are further corroborated in the

previous work by Kingdom and Swain,8 who notedhigh rates of quinolone resistance for SCN (21% ofpatients) and S aureus (21% of patients). Also, thehigh rate of resistance to methicillin was furtherexemplified among S aureus isolates in 21% ofpatients. Lastly, P aeruginosa isolates showeda 27% resistance rate to quinolones and 36%resistance rate to aminoglycosides.Guss and colleagues22 retrospectively reviewed

all bacterial sinus cultures from a tertiary care rhi-nology practice that yielded P aeruginosa over a 5-year period. A total of 689 culture results from 324patients were examined. Overall, 13% of all P aer-uginosa cultured were resistant to levofloxacin,with 5% intermediately sensitive. Moreover, 5%were resistant to ciprofloxacin while 7% wereintermediately sensitive. The resistance rates re-mained stable throughout the 5-year study period.The use of endoscopically derived cultures wascrucial in ascertaining this high rate of fluoroquino-lone resistance, supporting the use of culture-specific therapy.

SUMMARY

This snapshot of bacteriologic data highlights theinherent difficulties in managing the infectiousaspects of CRS. Although SCN, S aureus, and Paeruginosapredominate inmicrobiological studies,a multitude of gram-negative rods and other atyp-ical organisms may also be cultures in refractoryCRS, especially in the setting of previous sinussurgery. Selective pressures posed by antimicro-bial therapy and the emergence of antibiotic resis-tance further add to the complexity of themanagement strategy. Thus, indiscriminate use ofbroad-spectrum antibiotic therapy should bediscouraged. Targeted use of antibiotic therapy,specifically for infectious exacerbations of CRSbasedon endoscopically guided cultures, is prefer-able. A careful, judicious strategy will optimize thecare of the aesthetic and reconstructive surgerypatients when medical and surgical managementof CRS is required concurrently with rhinoplastyor in a staged manner.

Bacteriology and Antibiotic Resistance in CRS 91

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