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Table 1. 
Profile of Pediatric Patients With Persistent Acute Otorrhea and Acute Otitis Media Caused by Community-Acquired Methicillin-Resistant Staphylococcus aureus
Profile of Pediatric Patients With Persistent Acute Otorrhea and Acute Otitis Media Caused by Community-Acquired Methicillin-Resistant Staphylococcus aureus
Table 2. 
Resistance Profile of Community-Acquired Methicillin-Resistant Staphylococcus aureus in Pediatric Patients With Persistent Acute Otorrhea and Acute Otitis Media
Resistance Profile of Community-Acquired Methicillin-Resistant Staphylococcus aureus in Pediatric Patients With Persistent Acute Otorrhea and Acute Otitis Media
1.
Freid  VMMakuc  DMRooks  RN Ambulatory health care visits by children: principal diagnosis and place of visit. Vital Health Stat 13 1998;1371- 23
PubMed
2.
Bondy  JBerman  SGlazner  JLezotte  D Direct expenditures related to otitis media diagnoses: extrapolations from a pediatric medicaid cohort. Pediatrics 2000;105E72
PubMedArticle
3.
Alsarraf  RJung  CJPerkins  JCrowley  CAlsarraf  NWGates  GA Measuring the indirect and direct costs of acute otitis media. Arch Otolaryngol Head Neck Surg 1999;12512- 18
PubMedArticle
4.
Gates  GA Cost-effectiveness considerations in otitis media treatment. Otolaryngol Head Neck Surg 1996;114525- 530
PubMedArticle
5.
Manolidis  SFriedman  RHannley  M  et al.  Comparative efficacy of aminoglycoside versus fluoroquinolone topical antibiotic drops. Otolaryngol Head Neck Surg 2004;130(suppl)S83- S88
PubMedArticle
6.
Nakamura  MMRohling  KLShashaty  MLu  HTang  YWEdwards  KM Prevalence of methicillin-resistant Staphylococcus aureus nasal carriage in the community pediatric population. Pediatr Infect Dis J 2002;21917- 922
PubMedArticle
7.
Hussain  FMBoyle-Vavra  SDaum  RS Community-acquired methicillin-resistant Staphylococcus aureus colonization in healthy children attending an outpatient pediatric clinic. Pediatr Infect Dis J 2001;20763- 767
PubMedArticle
8.
Santos  FMankarious  LAEavey  RD Methicillin-resistant Staphylococcus aureus: pediatric otitis. Arch Otolaryngol Head Neck Surg 2000;1261383- 1385
PubMedArticle
9.
Johnigan  RHPereira  KDPoole  MD Community-acquired methicillin-resistant Staphylococcus aureus in children and adolescents: changing trends. Arch Otolaryngol Head Neck Surg 2003;1291049- 1052
PubMedArticle
10.
Marcinak  JFFrank  AL Treatment of community-acquired methicillin-resistant Staphylococcus aureus in children. Curr Opin Infect Dis 2003;16265- 269
PubMedArticle
11.
Frank  ALMarcinak  JFMangat  PDSchreckenberger  PC Community-acquired and clindamycin-susceptible methicillin-resistant Staphylococcus aureus in children. Pediatr Infect Dis J 1999;18993- 1000
PubMedArticle
12.
Fergie  JEPurcell  K Community-acquired methicillin-resistant Staphylococcus aureus infections in south Texas children. Pediatr Infect Dis J 2001;20860- 863
PubMedArticle
13.
Leiberman  ALeibovitz  EPiglansky  L  et al.  Bacteriologic and clinical efficacy of trimethoprim-sulfamethoxazole for treatment of acute otitis media. Pediatr Infect Dis J 2001;20260- 264
PubMedArticle
14.
Dowell  SFButler  JCGiebink  GS  et al.  Acute otitis media: management and surveillance in an era of pneumococcal resistance: a report from the Drug-resistant Streptococcus pneumoniae Therapeutic Working Group. Pediatr Infect Dis J 1999;181- 9
PubMedArticle
15.
Iyer  SJones  DH Community-acquired methicillin-resistant Staphylococcus aureus skin infection: a retrospective analysis of clinical presentation and treatment of a local outbreak. J Am Acad Dermatol 2004;50854- 858
PubMedArticle
16.
Sattler  CAMason  EO  JrKaplan  SL Prospective comparison of risk factors and demographic and clinical characteristics of community-acquired, methicillin-resistant versus methicillin-susceptible Staphylococcus aureus infection in children. Pediatr Infect Dis J 2002;21910- 917
PubMedArticle
17.
Loeb  MMain  CWalker-Dilks  CEady  A Antimicrobial drugs for treating methicillin-resistant Staphylococcus aureus colonization [database online]. Cochrane Database Syst Rev 2003;4CD003340
PubMed
18.
Klein  JO In vitro and in vivo antimicrobial activity of topical ofloxacin and other ototopical agents. Pediatr Infect Dis J 2001;20102- 103, 120, 122
PubMedArticle
19.
Miro  N Controlled multicenter study on chronic suppurative otitis media treated with topical applications of ciprofloxacin 0.2% solution in single-dose containers or combination of polymyxin B, neomycin, and hydrocortisone suspension. Otolaryngol Head Neck Surg 2000;123617- 623
PubMedArticle
20.
Tong  MCWoo  JKvan Hasselt  CA A double-blind comparative study of ofloxacin otic drops versus neomycin-polymyxin B-hydrocortisone otic drops in the medical treatment of chronic suppurative otitis media. J Laryngol Otol 1996;110309- 314
PubMedArticle
21.
Jinn  THKim  PDRussell  PTChurch  CAJohn  EOJung  TT Determination of ototoxicity of common otic drops using isolated cochlear outer hair cells. Laryngoscope 2001;1112105- 2108
PubMedArticle
22.
Morpeth  JFBent  JPWatson  T A comparison of cortisporin and ciprofloxacin otic drops as prophylaxis against post-tympanostomy otorrhea. Int J Pediatr Otorhinolaryngol 2001;6199- 104
PubMedArticle
23.
Weber  SGGold  HSHooper  DCKarchmer  AWCarmeli  Y Fluoroquinolones and the risk for methicillin-resistant Staphylococcus aureus in hospitalized patients. Emerg Infect Dis 2003;91415- 1422
PubMedArticle
24.
Walsh  TJStandiford  HCReboli  AC  et al.  Randomized double-blinded trial of rifampin with either novobiocin or trimethoprim-sulfamethoxazole against methicillin-resistant Staphylococcus aureus colonization: prevention of antimicrobial resistance and effect of host factors on outcome. Antimicrob Agents Chemother 1993;371334- 1342
PubMedArticle
Original Article
September 2005

Trimethoprim-Sulfamethoxazole Plus Topical Antibiotics as Therapy for Acute Otitis Media With Otorrhea Caused by Community-Acquired Methicillin-Resistant Staphylococcus aureus in Children

Author Affiliations

Author Affiliations: Departments of Pediatrics (Dr Al-Shawwa) and Microbiology, Collaborative Laboratory Services (Dr Wegner), Ottumwa Regional Health Center, Ottumwa, Iowa.

Arch Otolaryngol Head Neck Surg. 2005;131(9):782-784. doi:10.1001/archotol.131.9.782
Abstract

Objective  To report our experience in identification and treatment of acute otitis media (AOM) with otorrhea secondary to community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA), which is seen in children at increasing rates.

Design  Clinical and laboratory records were retrospectively reviewed between January 2003 and December 2003.

Setting  Primary pediatric clinic.

Patients  Six pediatric patients who had AOM with otorrhea caused by CA-MRSA.

Main Outcome Measures  Clinical resolution of AOM with otorrhea.

Results  All patients had acute-onset otorrhea associated with their AOM. Five patients had tympanostomy tubes and 1 had perforation of the tympanic membrane. None of the patients were responding to treatment with oral antibiotics (amoxicillin sodium–clavulanate potassium, cefpodoxime proxetil, and cefprozil) or fluoroquinolone ear drops (ofloxacin, ciprofloxacin). Specimens were obtained from the ears for cultures, and MRSA was present in the cultures. The organisms were resistant to levofloxacin and erythromycin in all patients and resistant to clindamycin hydrochloride in 2 patients. The cultures were sensitive to trimethoprim-sulfamethoxazole, gentamicin sulfate, rifampin, and vancomycin hydrochloride. All patients were treated successfully with oral trimethoprim-sulfamethoxazole and ear drops (gentamicin sulfate or polymyxin B sulfate–neomycin sulfate–hydrocortisone [Cortisporin]).

Conclusions  The rising rate of CA-MRSA as a cause for many pediatric infections is a major concern. It is very important to obtain cultures from patients with nonresponsive or persistent otorrhea with AOM to look for MRSA and determine the sensitivity of the pathogen to antibacterial therapy. Trimethoprim-sulfamethoxazole is a good choice for initial, empirical therapy when combined with a topical agent for AOM with otorrhea if CA-MRSA is suspected. Further studies are needed to determine whether there is a link between the overuse of topical fluoroquinolones in pediatric patients and the recent rising rate of CA-MRSA.

Acute otitis media (AOM) is the most common bacterial infection in children and accounts for as many as 30 million office visits to physicians annually.1 Proper treatment is critical because offending pathogens become increasingly resistant to antibiotics, and the cost of managing the disorder has exceeded 3 billion dollars per year.24 The microorganisms classically associated with AOM, Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis, account for a significant percentage of AOM that occurs in an ear with a tympanostomy tube (or with a perforation), especially in children younger than 2 years. However, Pseudomonas aeruginosa and Staphylococcus aureus also account for a significant percentage of infections (often >40%), especially in older children.5

Methicillin-resistant S aureus (MRSA) has been an emerging concern as a pathogen in the community in addition to hospitals and chronic care facilities and among drug abusers. Reports6,7 show that as many as 3% of healthy children carry MRSA in their nasopharynges. Most pediatric MRSA infections have been reported as skin infections. However, a few reports8,9 have mentioned MRSA as a cause of AOM. A recent article by Santos et al8 suggested that intravenous vancomycin hydrochloride treatment is necessary for the resolution of AOM caused by MRSA. Vancomycin is very expensive and requires 24-hour intravenous access and monitoring of its levels, which makes it inconvenient for the patient and the family. Linezolid is an oral alternative to vancomycin, but its cost, which is approximately $120 per day, limits its use to more severe and serious infections.

In this article, we report our experience in treating AOM with otorrhea caused by community-acquired MRSA (CA-MRSA) with oral trimethoprim-sulfamethoxazole and topical antibiotics.

METHODS

This study was conducted in a primary pediatric clinic in a rural community in the United States. We reviewed the laboratory and medical records for all patients younger than 18 years with cultures positive for MRSA between January and December 2003. Collected data included demographic information, anatomical sites of infection, clinical symptoms, treatment modalities, and the results of treatment. The sensitivity results of the antibiotic treatment were collected from the original laboratory records. Only patients who had cultures positive for CA-MRSA and who had AOM were included.

Swabs from the ears of patients were obtained for culture on sheep’s blood agar plates. Susceptibility testing of the S aureus isolates was performed using the Vitek 1 Legacy model automated instrument (BioMerieux Inc, Durham, NC), according to manufacturer’s instructions. Quality control of the instrument and susceptibility cards was conducted according to Clinical and Laboratory Standards Institute regulations. Confirmation of resistance to methicillin was accomplished by using the Kirby-Bauer cefoxitin disk (Remel Inc, Lenexa, Kan) diffusion method specified by the Clinical and Laboratory Standards Institute.

RESULTS

Eleven patients were found to be MRSA positive; 5 had soft tissue and skin infections rather than otitis media and therefore were excluded from the study. The remaining 6 patients did have otitis media (Table 1). None had been recently hospitalized, and all of the infections appeared to be community-acquired infection.

Five patients had tympanostomy tubes, and 1 patient had a preexisting tympanic membrane perforation. All patients had new onset of otorrhea that was not responding to oral antibiotics (amoxicillin sodium–clavulanate, cefpodoxime proxetil, cefprozil) and fluoroquinolone ear drops (ofloxacin, ciprofloxacin). Ear culture specimens were obtained only when there was no response to these antibiotics. The organisms were sensitive to trimethoprim-sulfamethoxazole, gentamicin sulfate, rifampin, and vancomycin in all patients (Table 2). All patients were treated successfully (ie, the otorrhea resolved within the treatment period of 10-14 days) with oral trimethoprim-sulfamethoxazole (8-10 mg/kg per day) plus a topical agent. The topical agents used were gentamicin sulfate (3 patients), polymyxin B sulfate–neomycin sulfate–hydrocortisone (2 patients), and ofloxacin (1 patient). The patient who received ofloxacin ear drops carried an MRSA isolate that was resistant to levofloxacin, which suggests that trimethoprim-sulfamethoxazole alone may have cleared the infection. Follow-up examinations were conducted after 2 to 3 weeks to document resolution of ear drainage. None of the patients needed tympanostomy tube removal or irrigation because they had new onset of drainage and responded to modified treatment.

COMMENT

The pathogen MRSA is increasingly found in children. Most of the reported cases of CA-MRSA in children are soft tissue and skin infections and rarely have been reported812 as a cause of AOM. In this study, we report CA-MRSA as a causative bacteria for AOM with persistent tube or perforation otorrhea. All patients were treated successfully with trimethoprim-sulfamethoxazole oral antibiotics and with either topical gentamicin sulfate or polymyxin B sulfate–neomycin–hydrocortisone (Cortisporin; Glaxo Wellcome Inc, Research Triangle Park, NC). Trimethoprim-sulfamethoxazole has lost its role in treating AOM empirically13,14 because of the resistance profile of S pneumoniae and H influenzae. However, most of the recent studies7,10,12,1517 and our sensitivity testing data show that CA-MRSA remains sensitive to trimethoprim-sulfamethoxazole.

One observation in our study is that all the patients were initially treated with ciprofloxacin or ofoxacin ear drops. Because of their safety profiles, fluoroquinolone ear drop preparations are replacing other otic antibiotics (ie, gentamicin sulfate, tobramycin, and polymyxin B sulfate–neomycin) in the treatment of otorrhea.5,1822 A recent study by Weber et al23 concluded that the exposure to ciprofloxacin and levofloxacin is a significant risk factor for increasing the prevalence of MRSA. Although ciprofloxacin and other fluoroquinolones are rarely used parenterally in pediatric patients, the topical use of these agents has been increasing. Further studies are needed to determine whether the recent rise of CA-MRSA in pediatric patients is linked to the overuse of fluoroquinolones as topical agents.

Community-acquired methicillin-resistant S aureus infection presents an increasing challenge in treating AOM with otorrhea. We have had success with oral therapy with trimethoprim-sulfamethoxazole plus topical gentamicin sulfate or Cortisporin. We are aware of studies showing that oral rifampin could be combined with trimethoprim-sulfamethoxazole in treating MRSA infection.15,24 However, to date, no studies have been performed in which this combination has been used to treat AOM with otorrhea.

This report identifies the importance of culturing otorrhea in any patient with persistent otorrhea (nonresponsive acute or chronic) because of the possibility of MRSA, a pathogen that may not come to mind and that may necessitate modifying therapy. Also, this study supports the use of trimethoprim-sulfamethoxazole with a topical antibiotic as initial, empirical therapy in suspected cases of CA-MRSA.

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Article Information

Correspondence: Baha A. Al-Shawwa, MD, Ottumwa Regional Health Center, 931 E Pennsylvania Ave, Ottumwa, IA 52501 (balshawwa@hotmail.com).

Submitted for Publication: December 20, 2004; accepted April 26, 2005.

Financial Disclosure: None.

References
1.
Freid  VMMakuc  DMRooks  RN Ambulatory health care visits by children: principal diagnosis and place of visit. Vital Health Stat 13 1998;1371- 23
PubMed
2.
Bondy  JBerman  SGlazner  JLezotte  D Direct expenditures related to otitis media diagnoses: extrapolations from a pediatric medicaid cohort. Pediatrics 2000;105E72
PubMedArticle
3.
Alsarraf  RJung  CJPerkins  JCrowley  CAlsarraf  NWGates  GA Measuring the indirect and direct costs of acute otitis media. Arch Otolaryngol Head Neck Surg 1999;12512- 18
PubMedArticle
4.
Gates  GA Cost-effectiveness considerations in otitis media treatment. Otolaryngol Head Neck Surg 1996;114525- 530
PubMedArticle
5.
Manolidis  SFriedman  RHannley  M  et al.  Comparative efficacy of aminoglycoside versus fluoroquinolone topical antibiotic drops. Otolaryngol Head Neck Surg 2004;130(suppl)S83- S88
PubMedArticle
6.
Nakamura  MMRohling  KLShashaty  MLu  HTang  YWEdwards  KM Prevalence of methicillin-resistant Staphylococcus aureus nasal carriage in the community pediatric population. Pediatr Infect Dis J 2002;21917- 922
PubMedArticle
7.
Hussain  FMBoyle-Vavra  SDaum  RS Community-acquired methicillin-resistant Staphylococcus aureus colonization in healthy children attending an outpatient pediatric clinic. Pediatr Infect Dis J 2001;20763- 767
PubMedArticle
8.
Santos  FMankarious  LAEavey  RD Methicillin-resistant Staphylococcus aureus: pediatric otitis. Arch Otolaryngol Head Neck Surg 2000;1261383- 1385
PubMedArticle
9.
Johnigan  RHPereira  KDPoole  MD Community-acquired methicillin-resistant Staphylococcus aureus in children and adolescents: changing trends. Arch Otolaryngol Head Neck Surg 2003;1291049- 1052
PubMedArticle
10.
Marcinak  JFFrank  AL Treatment of community-acquired methicillin-resistant Staphylococcus aureus in children. Curr Opin Infect Dis 2003;16265- 269
PubMedArticle
11.
Frank  ALMarcinak  JFMangat  PDSchreckenberger  PC Community-acquired and clindamycin-susceptible methicillin-resistant Staphylococcus aureus in children. Pediatr Infect Dis J 1999;18993- 1000
PubMedArticle
12.
Fergie  JEPurcell  K Community-acquired methicillin-resistant Staphylococcus aureus infections in south Texas children. Pediatr Infect Dis J 2001;20860- 863
PubMedArticle
13.
Leiberman  ALeibovitz  EPiglansky  L  et al.  Bacteriologic and clinical efficacy of trimethoprim-sulfamethoxazole for treatment of acute otitis media. Pediatr Infect Dis J 2001;20260- 264
PubMedArticle
14.
Dowell  SFButler  JCGiebink  GS  et al.  Acute otitis media: management and surveillance in an era of pneumococcal resistance: a report from the Drug-resistant Streptococcus pneumoniae Therapeutic Working Group. Pediatr Infect Dis J 1999;181- 9
PubMedArticle
15.
Iyer  SJones  DH Community-acquired methicillin-resistant Staphylococcus aureus skin infection: a retrospective analysis of clinical presentation and treatment of a local outbreak. J Am Acad Dermatol 2004;50854- 858
PubMedArticle
16.
Sattler  CAMason  EO  JrKaplan  SL Prospective comparison of risk factors and demographic and clinical characteristics of community-acquired, methicillin-resistant versus methicillin-susceptible Staphylococcus aureus infection in children. Pediatr Infect Dis J 2002;21910- 917
PubMedArticle
17.
Loeb  MMain  CWalker-Dilks  CEady  A Antimicrobial drugs for treating methicillin-resistant Staphylococcus aureus colonization [database online]. Cochrane Database Syst Rev 2003;4CD003340
PubMed
18.
Klein  JO In vitro and in vivo antimicrobial activity of topical ofloxacin and other ototopical agents. Pediatr Infect Dis J 2001;20102- 103, 120, 122
PubMedArticle
19.
Miro  N Controlled multicenter study on chronic suppurative otitis media treated with topical applications of ciprofloxacin 0.2% solution in single-dose containers or combination of polymyxin B, neomycin, and hydrocortisone suspension. Otolaryngol Head Neck Surg 2000;123617- 623
PubMedArticle
20.
Tong  MCWoo  JKvan Hasselt  CA A double-blind comparative study of ofloxacin otic drops versus neomycin-polymyxin B-hydrocortisone otic drops in the medical treatment of chronic suppurative otitis media. J Laryngol Otol 1996;110309- 314
PubMedArticle
21.
Jinn  THKim  PDRussell  PTChurch  CAJohn  EOJung  TT Determination of ototoxicity of common otic drops using isolated cochlear outer hair cells. Laryngoscope 2001;1112105- 2108
PubMedArticle
22.
Morpeth  JFBent  JPWatson  T A comparison of cortisporin and ciprofloxacin otic drops as prophylaxis against post-tympanostomy otorrhea. Int J Pediatr Otorhinolaryngol 2001;6199- 104
PubMedArticle
23.
Weber  SGGold  HSHooper  DCKarchmer  AWCarmeli  Y Fluoroquinolones and the risk for methicillin-resistant Staphylococcus aureus in hospitalized patients. Emerg Infect Dis 2003;91415- 1422
PubMedArticle
24.
Walsh  TJStandiford  HCReboli  AC  et al.  Randomized double-blinded trial of rifampin with either novobiocin or trimethoprim-sulfamethoxazole against methicillin-resistant Staphylococcus aureus colonization: prevention of antimicrobial resistance and effect of host factors on outcome. Antimicrob Agents Chemother 1993;371334- 1342
PubMedArticle
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