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 �:	Current bacteriology and antibiotic management of acute suppurative parotitis in the hospitalized patient: A retrospective study and literature review.

Mark W Steehler
Lake Erie College of Osteopathic Medicine
Millcreek Community Hospital
Ear Nose & Throat Specialists of Northwestern Pennsylvania
3580 Peach Street�Erie, Pennsylvania, USA 16508
 HYPERLINK "mailto:marksteehler@gmail.com" marksteehler@gmail.com

Andrew W Agnew
Lake Erie College of Osteopathic Medicine
Erie, Pennsylvania, USA

Jack B Anon
Ear Nose & Throat Specialists of Northwestern Pennsylvania
Erie, Pennsylvania, USA



Running title: Acute bacterial suppurative parotitis

Key words: Acute  bacterial suppurative parotitis (ABSP), methicillin-resistant Staphylococcus aureus (MRSA), multi-drug resistant organisms (MDROs)

Summary:
Background
	Acute bacterial suppurative parotitis (ABSP) warrants prompt diagnosis and efficacious treatment with empiric broad spectrum antibiotics and maintenance of hydration. Patients can quickly deteriorate leading to increased morbidity and mortality. Bacterial parotitis has increasingly shown resistance to many traditionally recommended empiric antimicrobial agents.
Aim
	The aim of this study was to determine optimal empiric treatment for patients hospitalized with ABSP.
Methods
A retrospective chart review was conducted over a one year time period on all patients hospitalized with ABSP, analyzing patient demographics, bacterial cultures, and antibiotic sensitivities.
Findings
	Nine patients were identified over a one year time period hospitalized with ABSP. Fourteen cultures were isolated made up of eight unique bacterial species. Staphylococcus aureus (SA) made up 43% (6/14) of all pathogenic bacteria, four of which were methicillin-resistant Staphylococcus aureus (MRSA). Three patients in the cohort failed antibiotic treatment at some point due to bacterial resistance. Multi-drug resistant organisms (MDROs) made up 75% (6/8) of all isolates in which sensitivities were obtained.
Conclusion
As multidrug-resistant organisms (MDROs), specifically Staphylococcus aureus, continue to become more prevalent, empiric antibiotics must be appropriately selected to treat for these organisms until culture and sensitivity results become available. This study supports that all adults hospitalized with ABSP be started on IV vancomycin empirically, or linezolid if allergic to vancomycin.

Introduction:
The parotid gland is the largest salivary gland of the human body, and consequently, the most commonly affected by inflammation.1 The first known description of parotitis in the literature dates back to 800 BCE by Hippocrates, with the first English-language account of the disease coming in 1834 by Sir Benjamin Collins Brodie.2,3 Parotitis is characterized by facial pain, swelling, and erythema overlying the parotid gland. Acute bacterial parotitis can be differentiated from other diseases of the parotid by the ability to express purulent drainage from Stensen's duct through massage of the gland.1,4,5 Among adults, bacterial parotitis tends to occur more often in the elderly.1 Severe complications include deep neck space infection, Lemierre's syndrome, mediastinitis, necrotizing fasciitis, and death in some cases.4,5,6,7
The bacterial etiology of parotitis is thought to be from retrograde flow of oral flora through Stensen's duct, hematogenous seeding, or xerostomia.1,4,5,8 Xerostomia can be the result of dehydration, or from a multitude of drugs, including antidepressants, antihistamines, anticholinergics, and diuretics.1,4,5 Other risk factors include malnutrition, immunosuppression, surgery, and obstruction from either sialolithiasis, neoplasm, or stricture.1,2,4,5,9
Prevention remains key in the management of ABSP, especially among the elderly population. This includes, adequate hydration, good oral hygiene, and limiting offending medications whenever possible.1 Treatment includes volume repletion, sialogogues, warm compress, and frequent massage.1,4,5
Staphylococcus aureus is the most common bacterial pathogen causing ABSP, both historically and in recent studies.1,4,8,10 While antibiotics should be tailored to specific bacterial cultures and sensitivities once available, proper empiric antibiotic treatment is critical in successfully treating the disease.4 Traditionally a penicillin with a beta-lactamase inhibitor or first-generation cephalosporin has been recommended.1,4,5 Other antibiotic recommendations have included clindamycin.  Despite these recommendations, multidrug-resistant organisms (MDROs) are becoming more prevalent, rendering the aforementioned antibiotics useless.
The purpose of this study is to evaluate bacterial etiology and determine appropriate antibiotic management of acute suppurative parotitis. A retrospective chart review was conducted on all patients hospitalized at our institutions. Bacterial cultures and antibiotic sensitivities were analyzed in addition to clinicopathologic findings. A review of the literature is also presented.
 
Methods:
With Institutional Review Board approval, we performed a retrospective review of all hospitalized patients diagnosed with acute bacterial parotitis seen in consultation from February 2013 to February 2014. Various data was gathered, including patient demographics such as age, race, and gender, along with hospital duration, discharge disposition, bacteremia, and consultation with Infectious Disease, bacterial etiology, antibiotic treatment, antibiotic sensitivities, and minimum inhibitory concentrations.

Results:
            A total of nine patients were hospitalized over a one year time period. The average age was approximately 75 years old. Infectious disease was consulted 78% of the time (7/9). Bacteremia from parotitis was found to be present in 50% of patients in which blood cultures were obtained (3/6). Discharge disposition varied greatly among the cohort, including home, skilled nursing facility, transitional care unit, home hospice, and palliative care arrest. The average length of hospital stay was 10 days (Figure 1).
Of the nine patients diagnosed with acute parotitis, fourteen bacterial cultures were isolated. These bacterial cultures were obtained from purulence expressed through Stensen�s duct. The fourteen cultures obtained were made up of eight unique bacterial species. Sensitivities with minimum inhibitory concentrations were obtained on eight of the fourteen bacterial cultures. Staphylococcus aureus (SA) made up 43% (6/14) of all pathogenic bacteria. Other bacteria identified were �-hemolytic Streptococcus groups B and F, viridans group Streptococcus, Lactobacillus species, Serratia marcescens, Stenotrophomonas maltophilia, and diptheroids. MDROs made up 75% (6/8) of all isolates in which sensitivities were obtained. SA made up 67% (4/6) of all MDROs; the other two being Serratia marcescens and Stenotrophomonas maltophilia. Of the SA strains identified as MDROs, 100% (4/4) were methicillin-resistant Staphylococcus aureus (MRSA) (Figure 2).
Among patients diagnosed with SA parotitis, 50% of SA showed resistance to at least one of the antibiotics used over the course of treatment (3/6). Two patients were treated with intravenous clindamycin as an inpatient, and one was treated with oral cephalexin as an outpatient, all of which were later found to be ineffective antibiotics based on sensitivities. Cultures of SA were found to be resistant to cefazolin 67% (4/6) of the time, clindamycin 33% (2/6), erythromycin 67% (4/6), oxacillin 67% (4/6) and tetracycline 17% (1/6) (Figure 3).
 
Discussion:
Our otolaryngology practice has noted an increasing number of hospitalized patients with MDRO parotitis. Over a 12 month span, we�ve identified nine adults seen in hospital consultation by our otolaryngology service with acute bacterial suppurative parotitis (ABSP), six of which were due to MDROs; MRSA being the most common bacterial etiology. Historically, MDROs have been a rare cause of parotitis. These findings have prompted us to further investigate the bacterial etiology of adults hospitalized with ABSP. To our knowledge, this is the first retrospective study analyzing sensitivities and minimum inhibitory concentrations of pathologic bacteria cultured from acute suppurative parotitis.
A review of the literature conducted for all English-language original research published over the last twenty years on the microbiology of adult parotitis, excluding case reports and articles related to mumps, revealed only one such study of more than three patients. Brooks et al reviewed 32 specimens collected from patients with ABSP.11 Fifty five bacterial isolates were identified, 25 being aerobic and 30 anaerobic, with the most common organism being Staphylococcus aureus. In our study, we found Staphylococcus aureus to make up nearly half of all isolated bacteria.
While Staphylococcus aureus is the most common bacterial pathogen causing acute suppurative parotitis, MRSA is of increasing prevalence.12 A literature review revealed twelve reported cases of adult ABSP caused by MRSA. Outcomes varied widely from complete resolution without sequelae to death.12,13,14,15,16,17,18,19,20,21
MRSA comprised 67% of all cultured Staphylococcus aureus in our study. Also of note, all MRSA strains were found to be resistant to multiple other antibiotics. While some have advocated the use of vancomycin or linezolid when MRSA is suspected, we argue that since Staphylococcus aureus is by far the most common cause of ABSP, and the majority of Staphylococcus aureus parotitis is found to be MRSA, one should always have a high level of suspicion for MRSA as the cause of parotitis and treat with empiric antibiotics as such.1,5,7
Traditionally, a penicillinase-resistant penicillin or first-generation cephalosporin has been recommended.1,4,5 Our previous practice was to treat hospitalized patients with parotitis empirically with intravenous ampicillin/sulbactam or clindamycin while awaiting cultures and sensitivities in order to cover for the most common pathogens. However, ABSP has increasingly shown resistance to many of these traditionally recommended empiric antimicrobial agents. Three bacterial isolates in this study showed resistance to at least one antibiotic used over the course of treatment, resulting in longer hospital stays, increased morbitidity, and in the case of one particular patient, transfer from a general floor to the intensive care unit. Due to this high prevalence of MDRO parotitis, we suggest a change in empiric antibiotic coverage on all adults hospitalized with acute parotitis to include IV vancomycin while awaiting more specific treatment tailored to culture and sensitivity results. If the patient is allergic to vancomycin, then IV linezolid should be considered.
While Brooks et al advocates needle aspiration of the parotid gland as the best method to identify the causative organism, the bacterial cultures obtained in this study were from purulence expressed through Stensen�s duct.1 It has been said that cultures from Stensen�s duct are certain to be contaminated with oropharyngel bacteria. However, we found that the cultures in this study correlated with blood cultures whenever bacteremia was present. Potential future research would include a larger sample size with increased geographic diversity. As there are only adults in our cohort, we limited the study and literature review to the adult population. However, microbial data may similarly hold true to the pediatric population as well. Further studies are needed to verify this. Lastly, this study analyzes only patients hospitalized with acute  parotitis. Obviously IV antibiotics are not a reasonable choice for empiric antibiotic therapy in the outpatient setting. Moreover, the bacterial etiology and resistance level of patients treated in an outpatient setting may be significantly different to those hospitalized with parotitis. Future studies in this area are merited as well.

Conclusion:
ABSP warrants prompt diagnosis and efficacious treatment with empiric broad spectrum antibiotics and maintenance of hydration. Patients can quickly deteriorate leading to increased morbidity and mortality. Bacterial parotitis has increasingly shown resistance to many traditionally recommended empiric antimicrobial agents. As multidrug-resistant organisms (MDROs), specifically Staphylococcus aureus, continue to become more prevalent, empiric antibiotics must be appropriately selected to treat for these organisms until culture and sensitivity results become available. Thus, it�s recommended, based on the findings in this study, that all adults hospitalized with ABSP be started on IV vancomycin empirically, or linezolid if allergic to vancomycin.


References:
1.	Brook I. Acute bacterial suppurative parotitis: Microbiology and management. J Craniofac Surg 2003; 14: 37-40.

2.	Hippocrates, Adams F. Of the Epidemics. Whitefish, MT: Kessinger Publishing 2010.

3.	Brodie BC. Inflammation of the parotid gland and salivary fistulae. Lancet 1834; 23: 450-2.

4.	Fattahi TT, Lyu PE, Van Sickels JE. Management of acute suppurative parotitis. J Oral Maxillofac Surg 2002; 60: 46-8.

5.	Al-Dajani N, Wootton SH. Cervical lymphadenitis, suppurative parotitis, thyroiditis, and infected cysts. Infect Dis Clin North Am 2007; 21: 523-41.

6.	Lemierre A. On certain septicemias due to anaerobic organisms. Lancet 1936; 2: 701-3.

7.	Knepil GJ, Fabbroni G. A life-threatening complication of acute parotitis. Br J Oral Maxillofac Surg 2008; 46: 328-9.

8.	Bradley PJ. Microbiology and management of sialadenitis. Curr Infect Dis Resp 2002; 4: 217-224.

9.	Belczak SG, de Cleva R, Utiyama EM, Cecconello I, Rasslan S, Parreira JG. Acute postsurgical suppurative parotitis: Current prevalence at Hospital das Clinicas, Sao Paulo University Medical School. Rev Inst Med trop S Paulo 2008; 50: 303-5.

10.	Petersdorf RG, Forsyth BR, Bernake D. Staphylococcal Parotitis. N Engl J Med 1958; 259: 1250-1254.

11.	Brook I. Aerobic and anaerobic microbiology of suppurative sialadenitis. J Med Microbiol 2002; 51: 526�529.

12.	Enoch DA, Kara JA, Emery MM, Borland C. Two cases of parotid gland infection with bacteraemia due to methicillin-resistant Staphylococcus aureus. J Med Microbiol 2006; 55: 463-5.

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