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


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


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


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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)


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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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introduction common otorhinolaryngological infections · 11/29/2019 2 the aerobic and anaerobic...

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