introduction common otorhinolaryngological infections · 11/29/2019 2 the aerobic and anaerobic...
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PRINCIPLE OF APPROPRIATE AZITHROMYCINE & FLUCONAZOLE USE IN MANAGEMENT ENT INFECTION
Nugroho SuharsonoDepartment of Otorhinolaryngology Head and Neck Surgery
St. Vincentius A Paulo Hospital Surabaya
Tatalaksana Infeksi Saluran Nafas
di Layanan Primer
Hotel Mercure - Surabaya, Nov 30th 20191
Introduction
Infections of the ENT constitute a tremendous number of physician office visits
It is Crucial that the otorhinolaryngologist be familiar with that common infections and management of these disease processes
The antimicrobial especially fluconazole & azithromycin coverage is discussed in the management infections of the ENT
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Introduction
Fluconazole remains a first-line antifungal agent of choice for the treatment of C. albicans infections
Azithromycin are excellent alternatives to conventional agents in the treatment of infections of the respiratory tract.
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Common Otorhinolaryngological Infections
Oropharyngeal Candidiasis
Pharyngitis-Tonsilitis
Acute Otitis Media
Acute Bacterial Rhinosinusitis
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The aerobic and anaerobic bacteria isolated in upper respiratory tract and head and neck infections
Type of infection Aerobic and facultativeorganisms
Anaerobic organism
OMA Streptococcus pneumoniaeHaemophilus influenzaeMoraxella catarrhalis
Peptostreptococcus spp.
OMC , Mastoiditis Staphylococcus aureusEscherichia coli Klebsiella pneumoniaePseudomonas aeruginosa
Pigmented Prevotella and Porphyromonas sppBacteroides sppFusobacterium spp. Peptostreptococcus spp.
Peritonsillar and retropharyngealabscess
Streptococcus pyogenesS. AureusS. pneumoniae
Fusobacterium sppPigmented Prevotella and Porphyromonasspp
Recurrent tonsillitis S. pyogenesH. influenzaeS. aureus
Fusobacterium spp
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Brook I. Antibiotic-Resistant Pathogens in Ear, Nose, and Throat Infections. In: Infections of the Ears, Nose, Throat, and Sinuses . M. L. Durand, D. G. Deschler, eds. © Springer International Publishing AG, part of
Springer Nature 2018 , https://doi.org/10.1007/978-3-319-74835-1_1 , p: 15-30
The aerobic and anaerobic bacteria isolated in upper respiratory tract and head and neck infections
Type of infection Aerobic and facultativeorganisms
Anaerobic organism
Rhinosinusitis: acute H. influenzaeS. pneumoniaeM. catarrhalis
Peptostreptococcus spp
Rhinosinusitis: chronic S. AureusS. PneumoniaeH. influenzae
Fusobacterium sppPigmented Prevotella and Porphyromonas spp
Cervical lymphadenitis S. AureusMycobacterium spp
Pigmented Prevotella and Porphyromonas spp.aPeptostreptococcus spp
Deep neck space Streptococcus sppStaphylococcus spp
Fusobacterium sppPeptostreptococcus spp
Odontogenic complications Streptococcus sppStaphylococcus spp
Pigmented Prevotella and Porphyromonas sppPeptostreptococcus spp
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Brook I. Antibiotic-Resistant Pathogens in Ear, Nose, and Throat Infections. In: Infections of the Ears, Nose, Throat, and Sinuses . M. L. Durand, D. G. Deschler, eds. © Springer International Publishing AG, part of
Springer Nature 2018 , https://doi.org/10.1007/978-3-319-74835-1_1 , p: 15-30
Oropharyngeal CandidiasisFungal infection can occur:
immunosuppressed patients, HIV, transplant patients, chronic systemic or inhaled steroid use, broad-spectrum antibiotics, radiation therapy, and diabetes mellitus.
Candida albicans is most common isolated organism, leading to “thrush”—apseudomembranous candidiasis infection of the oral cavity, oropharynx, and possibly larynx and cervical esophagus.
Wein RO, O’leary M. Stomatitis. In: Johnson JT, Rosen CA, eds. Bailey’s Head and Neck Surgery Otolaryngology. Fifth edition. Lippincott Williams & Wilkins. Philadelphia. 2014. P:736-756.
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Oropharyngeal CandidiasisClinical features :
Sign & symptom: creamy white, curd-like patches on the tongue and other oral mucosal surfaces. Dysphagia and odynophagia can be quite severe.
Diagnosis:
Gram stain or KOH preparation showing masses of hyphae, pseudohyphae & yeast form
Wein RO, O’leary M. Stomatitis. In: Johnson JT, Rosen CA, eds. Bailey’s Head and Neck Surgery Otolaryngology. Fifth edition. Lippincott Williams & Wilkins. Philadelphia. 2014. P:736-756.
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Treatment of Oropharyngeal Candidiasis (Cuesta CG, Pérez MGS, Bagán JV. Current treatment of oral candidiasis: A literature review. J Clin Exp Dent. 2014;6(5):e576-82)
Author/ Year
Article Sample Drug Conclusions
Manfredi et al. 2006
In vitro antifungal susceptibility to six antifungal agents of 229 Candida isolates from patients with diabetes mellitus
Clinical trialn=821
Itraconazole Miconazole Ketoconazole FluconazoleAmfotericin B
Those strains that were resistant to fluconazole also were resistant to other drugs.
Koray et al. 2005
Fluconazole and/or hexetidine for management of oral candidiasis associated with denture-induced stomatitis
Clinical trial n=61
Hexetidine rinseHeksoral® 0,1% FluconazoleZolax®
Supports the use of antiseptics or hexetidine as a first choice. Conservative intervention 9
Author/ Year
Article Sample Drug Conclusions
Koks et al. 2002
Prognostic factors for the clinical effectiveness of fluconazole in the treatment of oral candidiasis in HIV-1-infected individuals
Clinical trial n=28
Fluconazolecapsules Diflucan ®
Great efficacy of fluconazole
Lyon et al. 2006
Correlation between adhesion, enzyme production, and susceptibility to fluconazole in Candida albicans obtained from dentures wearers
Clinical trial n=99
FluconazolecapsulesItraconazole capsules
Fluconazole better result
Kuriyama et al. 2005
In vitro susceptibility of oral Candida to seven antifungal agents
Clinical trial n=521
Fluconazole Itraconazole Voriconazole Ketoconazole Miconazole Amfotericin b Nystatin
Some Candida species are resistant to antifungal drugs
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Author/ Year
Article Sample Drug Conclusions
Brito et al. 2011
In vitro antifungal susceptibility of Candida spp. Oral isolates from HIV-positive patients and control individuals
Clinical trial n=71 cepas de Cándida
Anfotericin b FluconazoleFlucytosine Nystatin Ketoconazole
Antifungal agents showed good activity against the strains
Ally et al. 2001
A randomized, double-blind, double-dummy, multicenter trial of voriconazole and fluconazole in the treatment of esophageal candidiasis in immunocompromised patients
Comparative clinical trial n=256
Fluconazole capsulesVoriconazole capsules
Voriconazole was at least as effective as fluconazole 11
Treatment of Oropharyngeal Candidiasis(based on four fundaments)
Making an early and accurate diagnosis of the infection
Correcting the predisposing factors or underlying diseases
Evaluating the type of Candida infection
Appropriate use of antifungal drugs, evaluating the efficacy / toxicity ratio in each case
Cuesta CG, Pérez MGS, Bagán JV. Current treatment of oral candidiasis: A literature review. J Clin Exp Dent. 2014;6(5):e576-82. 12
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Pharyngitis-TonsillitisPharyngitis-tonsillitis typically presents with
sore throat (odynophagia & dysphagia),fevers, hoarseness, nasal congestion, cough, halitosis, and malaise.
Viral infections are the most common cause(both children and adults).
Pediatric patients have a much higher rate of bacterial infection than adults (30% to 40% and 5% to 15%, respectively)
Hoff SR, Chang KW. Pharyngitis. In: Johnson JT, Rosen CA, eds. Bailey’s Head and Neck Surgery Otolaryngology. Fifth edition. Lippincott Williams & Wilkins. Philadelphia. 2014. P: 757-769.
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Infectius causes of Pharyngitis-TonsillitisGABHS :20-30% (children); 5-15% in adults
The incubation period :1 to 4 days Symptom Pharyngeal-tonsil examination
Sore throat & odynophagia FeversMalaise Headache Gastrointestinal symptoms
(abdominal pain, vomiting) Cough Coryza Nasal congestion
erythematous oropharyngeal mucosa
beefy red uvula soft palate petechiae Tonsils erythematous and
inflamed, and a whitish,creamy exudate
Hoff SR, Chang KW. Pharyngitis. In: Johnson JT, Rosen CA, eds. Bailey’s Head and Neck Surgery Otolaryngology. Fifth edition. Lippincott Williams & Wilkins. Philadelphia. 2014. P: 757-769.
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Diagnosis of GABHS
Depends on clinical judgment & laboratory testing
All guidelines recommend against further testing if the patient does not have symptoms typical of GABHS.
The gold standard laboratory test: pharyngeal swab, with culture on a blood-agar plate/“rapid-strep” (rapid antigen detection test: RADT, 90% to 99% sensitive)
Hoff SR, Chang KW. Pharyngitis. In: Johnson JT, Rosen CA, eds. Bailey’s Head and Neck Surgery Otolaryngology. Fifth edition. Lippincott Williams & Wilkins. Philadelphia. 2014. P: 757-769.
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Treatment of Pharyngitis-Tonsillitis
Tonsillitis should be treated in the same way as other causes of pharyngitis (with reassurance, rest and plenty of fluids)
The role of antibiotics is controversial
In a patient who is clinically deteriorating,antibiotics may be prescribed
Robson A. Infections of the pharynx Ed:Hussain SM. In: Logan Turner’s. Diseases of the Nose, Throat, Ear- Head and Neck Surgery. Elevent edition. Taylor & Francis Group, LLC. New York. 2016. P: 175-181.
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Treatment of Pharyngitis-TonsillitisSymptomatic therapy
Maintain adequate fluid intake
Warm salt water gargles
Soft food, flavored frozen desserts, warm liquids egg soup
Throat lozenges
Antipyretics & analgetics
Antibiotic therapy
Penicillin: drug of choice due to its proven efficacy & safety
Penicillin allergy, may be used:First-generation cephalosporins, azithromycin, or clindamycin
Azithromycin: the newer macrolides & better
tolerated. Has a higher concentrations in
pharyngeal tissue: only requires 5 days of treatment
– Tonsilopharyngitis Acute. In: MIMS Pharmacotherapy Guide to Infectious Diseases. UBC Medica. 2011. P: 136-146. 17
Acute Otitis Media
Otitis Media: general term used to describe inflamation of the middle ear, inflamation may be caused by an acute infection1
Symptoms: usually nonspecific,otalgia (pulling of ear in an infant), irritability , otorrhea, fever+/-, symptoms of URTI (cough, nasal discharge or stuffiness)1
Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis are the most common bacterial isolates from the middle ear fluid 2
1. Melvin TN, Ramanathan M. Microbiology, Infections, and Antibiotic Therapy. In: Johnson JT, Rosen CA, eds. Bailey’s
Head and Neck Surgery Otolaryngology. Fifth edition. Lippincott Williams & Wilkins. Philadelphia. 2014. P:131-140. 2. Ramakrishnan K, Sparks RA, Berryhill WE. Diagnosis and Treatment of Otitis Media. Am Fam Physician 2007;76:1650-8,
1659-60.18
Treatment Acute Otitis Media First-line treatment, simple analgesics,
paracetamol and/or ibuprofen (non-severe uncomplicated AOM)
Children < 6 months of age, all AOM cases should be treated with antibiotic
The first choice of antibiotic in primary care is usually penicillin
For penicillin allergic: erythromycin or azithromycin is prescribed
Morrison G. Acute otitis media and mastoiditis. Ed:Hussain SM. In: Logan Turner’s. Diseases of the Nose, Throat, Ear- Head and Neck Surgery. Elevent edition. Taylor & Francis Group, LLC. New York. 2016. P: 595-607.
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Acute Rhinosinusitis
Classification Duration of symptom The guidelines
Acute RS 4 weeks or less.less than 12 weeks
with complete resolution of symptoms
RI, JTFPP, and CPG:AS
EP3OS and BSACI
Meltzer EO, Hamilos DL. Rhinosinusitis Diagnosis and Management for the Clinician: A Synopsis of Recent Consensus Guidelines. Mayo Clin Proc. 2011;86(5):427-443
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Diagnosis Criteria of ARS
Signs & Simptoms Guideline
≥2 major symptoms, 1 ofwhich nasal discharge/ nasal blockage/ Congestion/obstruction; other symptoms can include facial pain/pressure/ reduction/ loss of smell
EP3OS (European Position Paper on Rhinosinusitis and Nasal Polyps 2007 & “2012”)
Meltzer EO, Hamilos DL. Rhinosinusitis Diagnosis and Management for the Clinician: A Synopsis of Recent Consensus Guidelines. Mayo Clin Proc. 2011;86(5):427-443 21
Etiology (Viral vs Bacterial)AVRS ABRS
ARS is most commonly viral in origin (eg, the commoncold), incidence AVRS is extremely high (2 to 5 times per year in an average adult)
Symptoms typically peak within 2 to 3 days of onset, decline gradually, and disappear within 10 to 14 days
Rhinovirus, influenza virus, and parainfluenza virus
Emphasis the duration, pattern, and/or severity of symptoms
Symptoms persisting for ≥10 days and/or showing a pattern of initial improvement followed by worsening (RI, JTFPP, CPG:AS, EP3OS)
Unusually severe symptoms (eg, high fever, unilateral facial/tooth pain, orbital cellulitis, intracranialexpansion) (RI, JTFPP, CPG:AS,BSACI)
Nasal mucus color, the presence of fever (JTFPP & CPG:AS)
Meltzer EO, Hamilos DL. Rhinosinusitis Diagnosis and Management for the Clinician: A Synopsis of Recent Consensus Guidelines. Mayo Clin Proc. 2011;86(5):427-443 22
Epidemiology of ARS ARS is highly prevalent, affecting 6-15% of the
population. ARS incidence and prevalence primary
care studies
Fokkens WJ, Lund VJ, Mullol J, Bachert C, et al. European Position Paper on Rhinosinusitis and Nasal Polyps 2012 . Rhinology Supplement 23, 2012. p: 9-53
Author, year Evidence
Uijen 2011 Incidence of ARS during 2002 to 2008:0-4 years: 2/1000 per year in all years5-14 years: 7/1000 in 2002 reducing to 4/1000 in 2008 (p<0.00112-17 years: 18/1000 per year in all years.
Oskarsson 2011 Incidence of ARS is 3.4 cases per 100 inhabitants per year, or 1 in 29.4patients visits their GP due to ARS
Wang 2011 6-10% of patients present at GP, otolaryngologist or paediatricoutpatient practices with ARS
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The Dynamics and Changes over time in The Microbiology of Bacterial Sinusitis (Maxillary)
Brook I. Microbiology of Sinusitis Proceedings of the American Thoracic Society vol 8 2011. P.90-100.
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Antibiotic Use in Acute Bacterial SinusitisIndications for
Antibiotic Treatment
Pathogen Antimicrobial Therapy
Antibiotic Guidelines Reviewed
When to Treat with
an Antibiotic:
symptoms of a viral
URI that have not
improved after 10 days or worsen after
5-7 days.
Streptococcus
pneumoniae
Nontypeable
Haemophilus
influenzae
Moraxella
catarrhalis
Antibiotic
Duration: 7 to 10
days
Failure to respond after 72
hours of
antibiotics:
Reevaluate
patient and
switch to
alternate
antibiotic.
1st Line:
• Amoxicillin
Alternatives:
• Amoxicillin-
clavulanate
• Oral cephalosporins:
not first generation
(i.e. cefpodoxime,cefuroxime, cefdinir,
etc.)
• Respiratory
quinolone
(levofloxacin,
moxifloxacin)
For ß-Lactam Allergy:
Trimethoprim-
sulfamethoxazole,
doxycycline,
azithromycin,clarithromycin
American Academy of
Allergy, Asthma &
Immunology (AAAAI)
American Academy of
Family Physicians (AAFP)American College of
Physicians (ACP)
Centers for Disease
Control and Prevention
(CDC)
Sinus and Allergy Health
Partnership (SAHP)
When NOT to Treat
with an Antibiotic:
Nearly all cases of
acute sinusitis
resolve without antibiotics.
Antibiotic use should
be reserved for
moderate and severe
symptoms.
Mainly viral
pathogens
Acute Respiratory Tract Infection Guideline Summary. 2012. CMA Foundation AWARE25
Antibiotic Therapy for Acute Rhinosinusitis
(10-14 day usual course)
First Line Antibiotic: Amoxicillin, Trimethoprim/sulfamethoxazole
Alternative First Line: Doxycycline, Azithromycin, Cefuroxime axetil,Clarithromycin, Cefprozil, Cefdinir.
Second Line: Amoxicillin high dose, Amoxicillin/clavulanate potassium, Levofloxacin, Moxifloxacin
UMHS Rhinosinusitis Guideline August 2011 26
Targets for Macrolide AntibioticsTarget Macrolide action Reference
Cytokine production Decreased IL-5, IL-8, GM-CSFDecreased TGF-bDecreased IL-6, IL-8, TNF-a
Wallwork, 2002Wallwork, 2004Suzuki, 1997
Biofilm formation Altered structure and function of biofilm
Wozniak, 2004
Leukocyte adhesion Reduced expression of cell surfaceadhesion molecules
Lin, 2000Matsouka, 1996
Apoptosis Accelerate neutrophil apoptosis Inamura, 2000Aoshiba 1995
Oxidative burst Impaired neutrophil oxidative burst Hand, 1990
Mucociliary clearance Decreased secretionsImproved clearance
Rubin, 1997Nishi, 1995
Bacterial virulence Inhibited release of elastase, protease, phospholipase C, and eotaxin A by P aeruginosa
Hirakata, 1992
Cervin A, Wallwork B. Anti-inflammatory Effects of Macrolide Antibiotics in the Treatment ofChronic Rhinosinusitis. Otolaryngol Clin N Am 38 (2005) 1339–1350.
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Treatment evidence and recommendations for ABRS (EP3OS 2012)
Therapy Level Grade ofrecommendation
Relevance
Antibiotic Ia A Yes in ABRS
Topical steroid Ia A Yes mainly in post viral ARS
Additional of topical steroid to antibiotic
Ia A Yes in ABRS
Additional of oral steroid to antibiotic
Ia A Yes in ABRS
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The Top Three Drugs (First-line Treatment by Physicians)
Severity ARS
Antibiotics Oral antihistamines
Decongestants
Pain relief
Mild 29.5 % 39.2 % 33.6 % -
Moderate 45.9 % 37.2 % 32.5 % -
Severe 60.3 % 37.6 % - 38.4 %
Wang DY, Wardani RS, Singh K, et al. A Survey on Management of Acute Rhinosinusitis among Asian Physicians. Rhinology 49: 264-271, 2011
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Percentage (%) of Drugs Used Dependingon Disease Severity
Drug Md Mo Sv Md Mo Sv Md Mo Sv
Decongest
87.6 %
79.3 %
77.2 %
89.2 %
83.9 %
87.8 %
96.1 %
87.3 %
84.1 %
Antibiotics
72.8 %
87.0 %
92.0 %
89.1 %
96.5 %
96.8 %
68.1 %
83.2 %
97.3 %
Antihistamines
91.7 %
81.9 %
82.7 %
75.1 %
68.1 %
70.4 %
100 %
82.7 %
88.2 %
GP (51.8%) ENT (39.2%) Ped (9%)
Wang DY, Wardani RS, Singh K, et al. A Survey on Management of Acute Rhinosinusitis among Asian Physicians. Rhinology 49: 264-271, 2011
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Summary
Understanding of the management of ENT infections needs further improvement to minimize overuse of antibiotics.
Clinicians must take into consideration: as well as factors known to affect patient adherence to antibiotic therapy, such as taste, tolerability, dosing schedule, duration of therapy, and patient preferences, when prescribtion.
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Summary
Azithromycin is active against most common upper respiratory bacterial pathogens
Azithromycin is convenient, short-course dosing in 3–5 day regimens has led to increased use in the community
Fluconazole remains a first-line antifungal agent of choice for the treatment of C. albicans infections, because of its well-known efficacy and safety profile;
Fluconazole is suitability for use in children, the elderly and patients with impaired immunity
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