Topical ofloxacin versus systemic amoxicillin/clavulanate in purulent otorrhea in children with tympanostomy tubes

doi:10.1016/S0165-5876(98)00150-5

International Journal of Pediatric Otorhinolaryngology

Volume 46, Issues 1–2, 15 November 1998, Pages 91-101

https://doi.org/10.1016/S0165-5876(98)00150-5 Get rights and content

Abstract

Acute otitis media (AOM) in children with tympanostomy tubes in place typically presents with otorrhea (draining ear). Because therapy is not standardized, various topical and systemic antibiotics of unproven efficacy and safety have been used in this indication. This study compared the safety and efficacy of ofloxacin otic solution, 0.3% (OFLX) with that of Augmentin® oral suspension (AUG) in pediatric subjects 1–12 years of age with tympanostomy tubes and acute purulent otorrhea. Subjects were randomized to receive 10d of OFLX, 0.25 ml topically bid, or of AUG, 40 mg/kg per day. Audiometry was performed in subjects ≥4 years of age. Overall cure rate for clinically evaluable subjects was 76% with OFLX (n=140) and 69% with AUG (n=146; P=0.169). Overall eradication rates for OFLX and AUG were similar for Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis and were superior with OFLX for Staphylococcus aureus and Pseudomonas aeruginosa (P<0.05 for both). OFLX had a greater overall pathogen eradication rate (96% vs. 67%; P<0.001). Treatment-related adverse event rates were 31% for AUG and 6% for OFLX (P<0.001). Neither treatment significantly altered hearing acuity. Topical ofloxacin 0.3% otic solution 0.25 ml bid was as effective and better tolerated than systemic therapy with Augmentin® oral suspension 40 mg/kg per day in treating AOM in children with tympanostomy tubes.

Introduction

When acute otitis media (AOM) occurs in children who have undergone tympanostomy tube insertion, its signs and symptoms as well as its pathogenic bacteria differ somewhat from those seen in children with intact tympanic membranes. Fever, systemic signs and otalgia are seldom seen in children with tympanostomy tubes unless there is a concomitant systemic infection. In children with tubes, otorrhea is the key symptom of AOM. It has been estimated to occur in 21–50% of all US patients with tympanostomy tubes 1, 2, 3.

Pathogens that cause AOM in children with intact tympanic membranes usually enter the middle ear from the pharynx via the Eustachian tube. In children with AOM and tympanostomy tubes, however, organisms that colonize the external auditory canal—such as Pseudomonas aeruginosa and Staphylococcus aureus—are often isolated from middle ear drainage in addition to those commonly associated with AOM in children with intact tympanic membranes 1, 4.

In 1997, ofloxacin otic solution, 0.3%, (OFLX) was approved by the FDA for treatment of AOM in pediatric patients of 1 year of age or older with tympanostomy tubes due to specified pathogens. The availability of OFLX offers a proven effective and safe alternative to nonstandardized treatment with other topical agents and to oral and intravenous antibiotics. Although many oral agents are generally effective in treating AOM in children with intact tympanic membranes, they may not be effective in children with tympanostomy tubes because of the different spectrum of pathogens associated with this disorder when tubes are present [5]. Use of topical agents that contain aminoglycosides is problematic, because they have caused ototoxicity in animals 6, 7.

In the United States, no oral antibiotic available for use in children is effective against P. aeruginosa and many of the available agents lack effectiveness against S. aureus, penicillin- and trimethoprim/sulfamethoxasole-resistant S. pneumoniae, or beta-lactamase producing strains of M. catarrhalis and H. influenzae 4, 8. Children with tympanostomy tubes may be at increased risk for resistant pathogens, since they are likely to have received several courses of oral antibiotics 9, 10, 11.

OFLX is effective in vitro against all pathogens associated with AOM in children with tympanostomy tubes, including P. aeruginosa, S. aureus, S. pneumoniae and beta–lactamase-producing strains of M. catarrhalis and H. influenzae. Topical administration of OFLX achieves high levels of ofloxacin in the middle ear, making the emergence of resistance unlikely. Because of its near-neutral pH (6.5) and lack of irritation in animal studies, OFLX is unlikely to irritate the middle ear mucosa. In an animal model study, topical OFLX was found to be nonototoxic [7].

The current study sought to compare the safety (especially with regard to ototoxicity) and the efficacy of OFLX to those of Augmentin® (AUG) oral suspension in the treatment of acute purulent otorrhea (draining ear) in pediatric subjects with tympanostomy tubes.

Section snippets

Study design

This was a multicenter, randomized, parallel-group, evaluator-blind study whose primary end point was overall clinical response (cure or failure, defined as the absence or presence of otorrhea). There were 36 study centers in the United States and one in Chile. Each center had an unblinded study coordinator who distributed medications, reviewed patient diaries and discussed compliance and adverse events with patients and parents. Physicians who served as evaluators performed physical

Results

A total of 474 intent-to-treat subjects were enrolled in the study, 228 treated with OFLX and 246 with AUG. The clinically evaluable subpopulation comprised 286 subjects, 140 treated with OFLX and 146 with AUG. Excluded from the clinically evaluable subpopulation were 88 intent-to-treat subjects in the OFLX arm and 100 intent-to-treat subjects in the AUG arm. The most common reasons for this exclusion were: baseline isolation of P. aeruginosa as the sole pathogen (20 OFLX-treated subjects and

Discussion

Recurrent AOM or chronic otitis media with effusion are common conditions presenting to the general pediatrician. The placement of a tympanostomy tube for drainage is usually looked upon as a solution to these conditions. Yet a significant number of patients develop AOM in the face of tube insertion, giving rise to troublesome otorrhea 1, 2, 3.

Current therapies used to treat AOM in children with tympanostomy tubes can be problematic. Aminoglycoside-containing topical treatments may result in

Conclusions

In this study, OFLX was as effective as AUG in effecting a clinical cure of AOM in children with tympanostomy tubes who did not have P. aeruginosa as a sole pathogen. OFLX was more effective than AUG in the eradication of S. aureus and P. aeruginosa and equally effective in the eradication of S. pneumoniae, H. influenzae and M. catarrhalis. Because P. aeruginosa as a sole pathogen is an important etiologic agent in this disorder—occurring in about 10% of subjects—coverage of this organism is an

Acknowledgements

This study was sponsored by the Daiichi Pharmaceutical Corporation. Additional data are available on request from Mindell Seidlin; Daiichi Pharmaceutical Corporation; One Parker Plaza; Fort Lee, NJ 07024.

References (14)

C.G Wright et al.
Ototoxicity of otic drops applied to the middle ear in the chinchilla
Am. J. Otol.
(1984)
M.K Zenni et al.
Streptococcus pneumoniae colonization in the young child: association with otitis media and resistance to penicillin
J. Pediatr.
(1995)
J.M Aran
Current perspectives on inner ear toxicity
Otolaryngol. Head Neck Surg.
(1995)
E.M Mandel et al.
Acute otorrhea: bacteriology of a common complication of tympanostomy tubes
Ann. Otol. Rhinol. Laryngol.
(1994)
F Herzon
Tympanostomy tubes: infectious complications
Arch. Otolaryngol. Head Neck Surg.
(1980)
C.A McClelland
Incidence of complications from use of tympanostomy tubes
Arch. Otolaryngol. Head Neck Surg.
(1980)
J.E Dohar et al.
Therapeutic implications in the treatment of aural Pseudomonas infections based on in vitro susceptibility patterns
Arch. Otolaryngol. Head Neck Surg.
(1995)

There are more references available in the full text version of this article.

Cited by (85)

The necessity and effect of prophylactic quinolone ear drops after ventilation tube insertion for otitis media with effusion
2022, American Journal of Otolaryngology - Head and Neck Medicine and Surgery
Citation Excerpt :
Pseudomonas aeruginos and Staphylococcus aureus are among the most common pathogens associated with post-tympanostomy tube otorrhea, and are robust biofilm formers [14]. Goldblatt et al. showed that topical ofloxacin was more effective than oral amoxicillin/clavulanate in the treatment of post-tympanostomy tube otorrhea when Pseudomonas aeruginos or Staphylococcus aureus was present, and was equally effective in the eradication of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis [9]. In the literature, the most common postoperative complication of tube insertion is otorrhea, with an incidence of 6–83% [15–18].
Otitis media with effusion (OME) is a condition where non-infective fluid builds up in the middle ear. Long-term OME can cause damage to the middle ear and hearing impairment. Ventilation tube insertion (VTI) is an efficient procedure to drain persistent OME. However, the effect of prophylactic ear drops after VTI remains controversial because no infection is present. This study investigated the need for and effect of quinolone ear drops in patients with OME after VTI.
Between July 2018 and July 2021, 272 patients (436 ears with OME) who underwent VTI were enrolled. Prophylactic quinolone ear drops (ofloxacin) were used in 271 OME ears and not used in 165. The clinical findings and effect of the ear drops were assessed.
The group with postoperative ofloxacin had less postoperative otorrhea (p < 0.001). In univariate analysis, age ≥ 13 years (odds ratio [OR] = 1.499, 95% confidence interval [CI]: 1.003–2.238, p = 0.046) was significantly associated with recovery to normal middle ear functioning (type A on postoperative tympanometry). No adenoid hypertrophy (OR = 1.692, 95% CI: 1.108–2.585, p = 0.014) and no postoperative otorrhea (OR = 2.816, 95% CI: 1.869–4.237, p < 0.001) were significant independent factors associated with middle ear recovery in both univariate and multivariate analysis. After VTI, 65% of tympanic membranes in the group with postoperative ofloxacin recovered to normal, while in 67% of tympanic membranes in the group without ofloxacin scarring remained.
Patients who received prophylactic postoperative ofloxacin had less postoperative otorrhea. No adenoid hypertrophy and no postoperative otorrhea were significant independent predictors of middle ear recovery to normal function in both univariate analysis and multivariate analysis. However, prophylactic ofloxacin was not an independent predictor of normal middle ear functioning after VTI. After VTI, most OME patients who had used ofloxacin postoperatively had eardrums that were in better condition than those of patients who had not used ofloxacin. In this study, we confirmed the advantages and limitations of OME after VTI with prophylactic ofloxacin, thus providing clinicians with some guidance regarding the decision to administer prophylactic ofloxacin.
Evidence-based telehealth clinical pathway for pediatric tympanostomy tube otorrhea
2020, International Journal of Pediatric Otorhinolaryngology
Citation Excerpt :
AAO-HNSF Guidelines state that clinicians should prescribe topical antibiotic eardrops only, without oral antibiotics, for children with acute, uncomplicated AOMT. Topical treatment is supported by randomized trials that demonstrated superior microbiologic eradication, clinical efficacy, and patient satisfaction with drops such as ofloxacin, ciprofloxacin, or ciprofloxacin-dexamethasone compared with systemic antibiotics such as amoxicillin or amoxicillin-clavulanate [2–4]. AAO-HNSF guidelines define acute AOMT as less than 4 weeks in duration, and uncomplicated by the absence of fever of 102° Fahrenheit or greater, signs of illnesses such as Group A streptococcal pharyngotonsillitis or bacterial sinusitis that may require systemic antibiotics, signs of cellulitis behind the ear, or immunocompromise [5].
As healthcare moves away from volume-based to value-based delivery models, evidence based clinical pathways detail essential steps in patient care to reduce the costs and utilization of health care resources. Ideal pathways lead towards standardized, patient-centered care through an algorithm that is evidence-based, interventions with criteria-based progression, and measurable endpoints or quality indicators. Using these standards, a clinical pathway for managing tympanostomy tube otorrhea beginning with phone triage was developed in accordance with AAO-HNSF Guidelines.
A retrospective case series of all consecutive patients calling the otolaryngology nurse's line at a tertiary pediatric hospital 3/2018-11/2018 regarding otorrhea was performed. Nurses completed a standardized and evidence-based form based on parent responses regarding purulence, tympanostomy tubes/perforation, fever>102°, ear redness, bacterial rhinosinusitis, sore throat, and immunodeficiency, which was sent to the advanced practice providers (APPs) to assess for antibiotic drops. Otorrhea form information and tympanostomy tube history, subsequent phone calls, clinic visits, and antibiotic prescriptions for otorrhea were extracted.
Eighty-two patients were included. Median child age at phone call was 2.5 years (range 0.3–20.2 years), and 45.1% were female. All patients had prior tubes and active purulent otorrhea. No parents reported cellulitis or immunodeficiency. One patient had symptoms of bacterial rhinosinusitis and a sore throat but had already been seen by their primary care provider (PCP) for systemic antibiotics. Antibiotic drops were prescribed by an APP in 96.3% of cases [ofloxacin (n = 57), ciprofloxacin (n = 17), or ciprofloxacin with dexamethasone (n = 5)]. The remaining patients already had drops (2.5%) or were referred to their PCP (1.2%). Twenty (24.4%) received another antibiotic prescription and 17.1% had a subsequent clinic or urgent care visit for otorrhea.
This pathway obviated clinic visits in 82.9% of patients with a 75.6% treatment cure.
Topical versus oral antibiotics, with or without corticosteroids, in the treatment of tympanostomy tube otorrhea
2016, International Journal of Pediatric Otorhinolaryngology
Antibiotic treatment is the standard of care for tympanostomy tube otorrhea. This meta-analysis aims to evaluate the efficacy of topical antibiotics with or without corticosteroids versus oral antibiotics in the treatment of tube otorrhea in children.
MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and ProQuest.
The above databases were searched using a search strategy for randomized controlled trials for optimal treatment of tube otorrhea in the pediatric population. PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines were followed. Primary outcome was cure (i.e. clearance of otorrhea) at 2–3 weeks. Secondary outcomes were microbiological eradication and complications such as dermatitis and diarrhea. The incidence of these events was defined as dichotomous variables and expressed as a risk ratio (RR) and number needed to benefit (NNTB) in a random-effects model.
We identified 1491 articles and selected 4 randomized controlled trials which met our inclusion criteria. Topical treatment had better cure (NNTB = 4.7, pooled RR = 1.35, p < 0.001) and microbiological eradication (NNTB = 3.5, pooled RR = 1.47, p < 0.001 among 3 of the studies) than oral antibiotics. Oral antibiotics had higher risk of diarrhea (pooled RR = 21.5, 95% CI 8.00–58.0, p < 0.001, Number needed to harm (NNTH) = 5.4) and dermatitis (pooled RR = 3.14, 95% CI 1.20–8.20, p = 0.019, NNTH = 32). The use of topical steroids in addition to topical antibiotics was associated with a higher cure rate (pooled RR = 1.59, p < 0.001 vs pooled RR = 1.57, p = 0.293).
Topical antibiotics should be the recommended treatment for management of tympanostomy tube otorrhea in view of its significantly improved clinical and microbiological efficacy with lower risk of systemic toxicity as compared to oral antibiotics. Further research is necessary to confirm the benefits of topical corticosteroids as an adjunct to topical antibiotics.
Contemporary concepts in management of acute otitis media in children
2014, Otolaryngologic Clinics of North America
Office Management of Tympanic Membrane Perforation and the Draining Ear
2010, Otologic Surgery
Current bacteriology of chronic otitis media with effusion: High rate of nosocomial infection and decreased antibiotic sensitivity
2009, Journal of Infection
Citation Excerpt :
Recently, however, atypical strains, including Staphylococcus aureus and Pseudomonas aeruginosa, have also been isolated from PTTO. These include antibiotic-resistant strains, including multi-drug resistant S. aureus (MRSA)5,6 and S. pneumoniae strains with high resistance to penicillin and trimethoprim/sulfamethoxazole (TMP/SMX).7,8 Changes in bacterial strains present and their antibiotic sensitivity may be caused by nosocomial infection or pre- and post-operative treatment with antibiotics.
Otitis media with effusion is a common disease entity in children, which is frequently managed surgically by insertion of a tympanostomy tube. Children who develop posttympanostomy tube otorrhea (PTTO) can be treated by administration of antibiotics. The abuse and misuse of antibiotics, however, has led to the emergence of resistant bacterial strains. We therefore examined the antibiotic sensitivity of bacterial strains collected from middle ear effusion fluid (MEEF) and PTTO. We also evaluated treatment outcomes in these patients.
This study was conducted in 289 patients who underwent tympanostomy tube insertion for chronic otitis media with effusion between March 2004 and February 2008.
Bacterial culture tests during the insertion of tympanostomy tubes showed a high frequency of coagulase(-) Staphylococcus (CNS), followed by Pseudomonas, methicillin resistant Staphylococcus aureus (MRSA) and methicillin-susceptible S. aureus (MSSA). Patients with PTTO had a high frequency of CNS and MRSA, followed by MSSA and Streptococcus pneumoniae. Overall antibiotic sensitivity was lower in postoperatively collected than in intraoperatively collected bacterial strains.
The bacterial strains detected in MEEF, and their antibiotic sensitivity profiles, differed somewhat from those of PTTO. Antibiotic sensitivity was decreased in bacteria from PTTO compared with those in MEEF.

View all citing articles on Scopus

View full text

Topical ofloxacin versus systemic amoxicillin/clavulanate in purulent otorrhea in children with tympanostomy tubes

Abstract

Introduction

Section snippets

Study design

Results

Discussion

Conclusions

Acknowledgements

Am. J. Otol.

J. Pediatr.

Otolaryngol. Head Neck Surg.

Acute otorrhea: bacteriology of a common complication of tympanostomy tubes

Ann. Otol. Rhinol. Laryngol.

Tympanostomy tubes: infectious complications

Arch. Otolaryngol. Head Neck Surg.

Incidence of complications from use of tympanostomy tubes

Arch. Otolaryngol. Head Neck Surg.

Therapeutic implications in the treatment of aural Pseudomonas infections based on in vitro susceptibility patterns

Arch. Otolaryngol. Head Neck Surg.