Antibióticos versus antisépticos tópicos para la otitis media supurativa crónica
Appendices
Appendix 1. Search strategies
| CENTRAL (the Cochrane Register of Studies) | MEDLINE (Ovid) | Embase (Ovid) |
|---|---|---|
| 1 MESH DESCRIPTOR Otitis Media EXPLODE ALL AND CENTRAL:TARGET | 1 exp Otitis Media/ 2 ("otitis media" or OME).ab,ti. 3 exp Tympanic Membrane Perforation/ 4 exp Tympanic Membrane/ 5 ("ear drum*" or eardrum* or tympanic).ab,ti. 6 4 or 5 7 (perforat* or hole or ruptur*).ab,ti. 8 6 and 7 9 1 or 2 or 3 or 4 or 8 10 exp Suppuration/ n 11 (suppurat* or pus or purulen* or discharg* or mucosal or otorrh* or otorh* or otoliquor* or active or weep* or moist or wet or mucopurulen* or discomfort or pain* or earach*).ab,ti. 12 10 or 11 13 exp Chronic Disease/ 14 exp Recurrence/ 15 (chronic* or persist* or recurr* or repeat*).ab,ti. 16 13 or 14 or 15 17 9 and 12 and 16 18 ((chronic or persist*) adj3 (ear or ears or aural) adj3 (suppurat* or pus or purulen* or discharg* or mucosal or otorrh* or otorh* or otoliquor* or active or weep* or wet or moist or mucopurulen* or pain* or discomfort)).ab,ti. 19 CSOM.ab,ti. 20 exp Otitis Media, Suppurative/ 21 (earach* adj6 (chronic or persist* or recurr* or repeat*)).ab,ti. 22 17 or 18 or 19 or 20 or 21 | 1 exp otitis media/ 2 ("otitis media" or OME).ab,ti. 3 exp eardrum perforation/ 4 exp eardrum/ 5 ("ear drum*" or eardrum* or tympanic).ab,ti. 6 4 or 5 7 (perforat* or hole or ruptur*).ab,ti. 8 6 and 7 9 1 or 2 or 3 or 8 10 exp suppuration/ 11 (suppurat* or pus or purulen* or discharg* or mucosal or otorrh* or otorh* or otoliquor* or active or weep* or moist or wet or mucopurulen* or discomfort or pain* or earach*).ab,ti. 12 10 or 11 13 exp chronic disease/ 14 exp recurrent disease/ 15 (chronic* or persist* or recurr* or repeat*).ab,ti. 16 13 or 14 or 15 17 9 and 12 and 16 18 exp suppurative otitis media/ 19 CSOM.ab,ti. 20 ((chronic or persist*) adj3 (ear or ears or aural) adj3 (suppurat* or pus or purulen* or discharg* or mucosal or otorrh* or otorh* or otoliquor* or active or weep* or wet or moist or mucopurulen* or pain* or discomfort or disease*)).ab,ti. 21 (earach* adj3 (chronic or persist* or recurr* or repeat*)).ab,ti. 22 17 or 18 or 19 or 20 or 21 |
| Web of Science (Web of Knowledge) | CINAHL (EBSCO) | Cochrane ENT Register (the Cochrane Register of Studies) |
| #1 TOPIC: ("otitis media" or OME) Indexes=SCI‐EXPANDED, SSCI, A&HCI, CPCI‐S, CPCI‐SSH, BKCI‐S, BKCI‐SSH, ESCI, CCR‐EXPANDED, IC Timespan=All years #2 TOPIC: (("ear drum*" or eardrum* or tympanic) AND (perforat* or hole or ruptur*)) Indexes=SCI‐EXPANDED, SSCI, A&HCI, CPCI‐S, CPCI‐SSH, BKCI‐S, BKCI‐SSH, ESCI, CCR‐EXPANDED, IC Timespan=All years #3 #2 OR #1 Indexes=SCI‐EXPANDED, SSCI, A&HCI, CPCI‐S, CPCI‐SSH, BKCI‐S, BKCI‐SSH, ESCI, CCR‐EXPANDED, IC Timespan=All years #4 TOPIC: ((suppurat* or pus or purulen* or discharg* or mucosal or otorrh* or otorh* or otoliquor* or active or weep* or moist or wet or mucopurulen* or discomfort or pain* or earach*) AND (chronic* or persist* or recurr* or repeat*)) Indexes=SCI‐EXPANDED, SSCI, A&HCI, CPCI‐S, CPCI‐SSH, BKCI‐S, BKCI‐SSH, ESCI, CCR‐EXPANDED, IC Timespan=All years #5 #4 AND #3 Indexes=SCI‐EXPANDED, SSCI, A&HCI, CPCI‐S, CPCI‐SSH, BKCI‐S, BKCI‐SSH, ESCI, CCR‐EXPANDED, IC Timespan=All years #6 TOPIC: (((chronic or persist*) NEAR/3 (ear or ears or aural) NEAR/3 (suppurat* or pus or purulen* or discharg* or mucosal or otorrh* or otorh* or otoliquor* or active or weep* or wet or moist or mucopurulen* or pain* or discomfort))) Indexes=SCI‐EXPANDED, SSCI, A&HCI, CPCI‐S, CPCI‐SSH, BKCI‐S, BKCI‐SSH, ESCI, CCR‐EXPANDED, IC Timespan=All years #7 TOPIC: ((earach* NEAR/3 (chronic or persist* or recurr* or repeat*))) Indexes=SCI‐EXPANDED, SSCI, A&HCI, CPCI‐S, CPCI‐SSH, BKCI‐S, BKCI‐SSH, ESCI, CCR‐EXPANDED, IC Timespan=All years #8 #7 OR #6 OR #5 Indexes=SCI‐EXPANDED, SSCI, A&HCI, CPCI‐S, CPCI‐SSH, BKCI‐S, BKCI‐SSH, ESCI, CCR‐EXPANDED, IC Timespan=All years | S21 S17 OR S18 OR S19 OR S20 S20 TX ((chronic or persist*) N3 (ear or ears or aural) N3 (suppurat* or pus or purulen* or discharg* or mucosal or otorrh* or otorh* or otoliquor* or active or weep* or wet or moist or mucopurulen* or pain* or discomfort)) S19 TX (earach* N3 (chronic or persist* or recurr* or repeat*)) S18 TX csom S17 S9 AND S12 AND S16 S16 S13 OR S14 OR S15 S15 TX chronic* or persist* or recurr* or repeat* S14 (MH "Recurrence") S13 (MH "Chronic Disease") S12 S10 OR S11 S11 TX suppurat* or pus or purulen* or discharg* or mucosal or otorrh* or otorh* or otoliquor* or active or weep* or moist or wet or mucopurulen* or discomfort or pain* or earach*) S10 (MH "Suppuration+") S9 S1 OR S2 OR S3 OR S8 S8 S6 AND S7 S7 TX perforat* or hole or ruptur* S6 S4 OR S5 S5 TX "ear drum*" or eardrum* or tympanic S4 (MH "Tympanic Membrane") S3 (MH "Tympanic Membrane Perforation") S2 TX "otitis media" or OME S1 (MH "Otitis Media+") | 1 ("otitis media" or OME):AB,EH,KW,KY,MC,MH,TI,TO AND INREGISTER 2 (("ear drum*" or eardrum* or tympanic)):AB,EH,KW,KY,MC,MH,TI,TO AND INREGISTER 3 (perforat* or hole or ruptur*):AB,EH,KW,KY,MC,MH,TI,TO AND INREGISTER 4 #2 AND #3 AND INREGISTER 5 #4 OR #1 AND INREGISTER 6 (suppurat* or pus or purulen* or discharg* or mucosal or otorrh* or otorh* or otoliquor* or active or weep* or wet or moist or discomfort or earach* or mucopurulen*):AB,EH,KW,KY,MC,MH,TI,TO AND INREGISTER 7 (pain):AB,TI,TO AND INREGISTER 8 #6 OR #7 AND INREGISTER 9 (chronic* or persist* or recurr* or repeat*):AB,EH,KW,KY,MC,MH,TI,TO AND INREGISTER 10 #5 AND #8 AND #9 AND INREGISTER 11 (csom):AB,EH,KW,KY,MC,MH,TI,TO AND INREGISTER 12 (((chronic* or persist* or recurr* or repeat*) and (ear or ears or aural) and (suppurat* or pus or purulen* or discharg* or mucosal or otorrh* or otorh* or otoliquor* or active or weep* or wet or moist or mucopurulen* or pain* or discomfort or disease*))):AB,EH,KW,KY,MC,MH,TI,TO AND INREGISTER 13 ((earach* and (chronic or persist* or recurr* or repeat*))):AB,EH,KW,KY,MC,MH,TI,TO AND INREGISTER 14 #10 OR #11 OR #12 OR #13 AND INREGISTER |
| ClinicalTrials.gov | ICTRP (WHO Portal) | Other |
| Search 1 (clinicaltrials.gov): (chronic OR persistent OR recurrence OR recurrent) AND (suppuration OR pus OR discharge OR otorrhea or active OR mucopurulent) AND Condition: "Otitis Media" OR OME AND Study type: interventional Search 2 (clinicaltrials.gov): (chronic OR persistent OR recurrence OR recurrent) AND (earache OR "ear ache" OR "ear pain" OR "ear discharge" OR "wet ear" OR "moist ear" OR "weeping ear") AND Study type: interventional Search 3 (clinicaltrials.gov): ("ear drum" OR eardrum OR "tympanic membrane") AND (hole OR perforation OR rupture) AND Study type: interventional Search 4 (the Cochrane Register of Studies): 1 ("otitis media" or OME):AB,EH,KW,KY,MC,MH,TI,TO AND INSEGMENT 2 (("ear drum*" or eardrum* or tympanic)):AB,EH,KW,KY,MC,MH,TI,TO AND INSEGMENT 3 (perforat* or hole or ruptur*):AB,EH,KW,KY,MC,MH,TI,TO AND INSEGMENT 4 #2 AND #3 AND INSEGMENT 5 #4 OR #1 AND INSEGMENT 6 (suppurat* or pus or purulen* or discharg* or mucosal or otorrh* or otorh* or otoliquor* or active or weep* or wet or moist or discomfort or earach* or Mucopurulen*):AB,EH,KW,KY,MC,MH,TI,TO AND INSEGMENT 7 (pain):AB,TI,TO AND INSEGMENT 8 #6 OR #7 AND INSEGMENT 9 (chronic* or persist* or recurr* or repeat*):AB,EH,KW,KY,MC,MH,TI,TO AND INSEGMENT 10 #5 AND #8 AND #9 AND INSEGMENT 11 (csom):AB,EH,KW,KY,MC,MH,TI,TO AND INSEGMENT 12 (((chronic* or persist* or recurr* or repeat*) and (ear or ears or aural) and (suppurat* or pus or purulen* or discharg* or mucosal or otorrh* or otorh* or otoliquor* or active or weep* or wet or moist or Mucopurulen* or pain* or discomfort or disease*))):AB,EH,KW,KY,MC,MH,TI,TO AND INSEGMENT 13 ((earach* and (chronic or persist* or recurr* or repeat*))):AB,EH,KW,KY,MC,MH,TI,TO AND INSEGMENT 14 #10 OR #11 OR #12 OR #13 AND INSEGMENT 15 (nct*):AU AND INSEGMENT 16 #14 AND #15 | otitis media AND chronic OR ear discharge OR earache OR wet ear OR weeping ear OR moist ear OR CSOM OR OME AND chronic OR tympanic membrane AND perforation OR eardrum AND hole OR eardrum AND perforation | LILACS TW:"otitis media" OR "TW:"ear discharge" OR TW:earache OR ((TW:eardrum OR TW:tympanic) AND (TW:perforation OR hole)) OR ((TW:wet OR moist OR weeping) AND TW:ear) AND: Filter: Controlled Clinical Trial IndMed Chronic Suppurative Otitis Media OR Chronic Otitis Media OR CSOM African Index Medicus “chronic suppurative otitis media" OR "chronic otitis media“ OR CSOM |
Appendix 2. Data extraction form
| REF ID: | Study title: |
| Date of extraction: | Extracted by: |
| Name and email address of correspondence authors: |
| General comments/notes (internal for discussion): |
FLOW CHART OF TRIAL:
| Intervention (name the intervention) | Comparison (name the intervention) | |
| No. of people screened | ||
| No. of participants randomised ‐ all | ||
| No. randomised to each group | ||
| No. receiving treatment as allocated | ||
| No. not receiving treatment as allocated ‐ Reason 1 ‐ Reason 2 | ||
| No. that dropped out1 (no follow‐up data for any outcome available) | ||
| No. excluded from analysis2 (for all outcomes) ‐ Reason 1 ‐ Reason 2 | ||
1This includes patients who withdrew and provided no data, or did not turn up for follow‐up.
2This should be the people who were excluded from all analyses (e.g. because the data could not be interpreted or the outcome was not recorded for some reason). This is the number of people who dropped out, plus the people who were excluded by the authors for some reason (e.g. non‐compliant).
INFORMATION TO GO INTO THE 'CHARACTERISTICS OF INCLUDED STUDIES' TABLE:
| Methods | X arm, double‐/single‐/non‐blinded, [multicentre] parallel‐group/cross‐over/cluster RCT, with x duration of treatment and x duration of follow‐up |
| Participants | Location: [country, rural?, no. of sites etc.] Setting of recruitment and treatment: [specialist hospital? general practice? school? state YEAR] Sample size:
Participant (baseline) characteristics:
Inclusion criteria:
Exclusion criteria: |
| Interventions | Intervention (n = x): drug name, method of administration, dose per day/frequency of administration, duration of treatment For aural toileting: who does it, methods or tools used, frequency, duration Comparator group(n = y): Concurrent treatment: Use of additional interventions (common to both treatment arms): |
| Outcomes | Outcomes of interest in the review: Primary outcomes:
Secondary outcomes
|
| Funding sources | "No information provided"/"None declared"/State source of funding |
| Declarations of interest | "No information provided"/"None declared"/State conflict |
| Notes | Clinical trial registry no: (if available) Unit of randomisation: person/ears/other (e.g. cluster‐randomised by hospital/school) [In the case of randomisation by person]: Methods for including patients with bilateral disease, for example:
|
RISK OF BIAS TABLE:
(See table 8.5d in the Cochrane Handbook for Systematic Reviews of Interventions: http://handbook.cochrane.org/).
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | High/low/unclear risk | Quote: "…" Comment: |
| Allocation concealment (selection bias) | High/low/unclear risk | Quote: "…" Comment: |
| Blinding of participants and personnel (performance bias) | High/low/unclear risk | Quote: "…" Comment: |
| Blinding of outcome assessment (detection bias) | High/low/unclear risk | Quote: "…" Comment: |
| Incomplete outcome data (attrition bias) | High/low/unclear risk | Quote: "…" Comment: |
| Selective reporting (reporting bias) | High/low/unclear risk | Quote: "…" Comment: |
FINDINGS OF STUDY
CONTINUOUS OUTCOMES
| Results (continuous data table) | |||||||
| Outcome | Intervention (name the intervention) | Comparison (name the intervention) | Other summary statistics/Notes | ||||
| Mean | SD | N | Mean | SD | N | Mean difference (95% CI), P values etc. | |
| Disease‐specific health‐related quality of life (COMQ‐12, COMOT‐15, CES)1 Time point: (state) | |||||||
| Hearing: [Measurement method: include frequencies and report results separately if they are presented in the paper] Time point: [xx] | |||||||
| Comments: [If there is no information apart from (vague) narration, quote here] [If information is in the form of graphs, used this software to read it: http://arohatgi.info/WebPlotDigitizer/app/, and save a copy of your charts in a folder] | |||||||
1State the measurement method: this will be instrument name/range for patient‐reported outcomes.
DICHOTOMOUS OUTCOMES
| Results (dichotomous data table) | ||||||
| Outcome | Applicable review/ Intervention1 | Group A ‐ intervention arm | Group B – control | Other summary statistics/Notes | ||
| No. of people with events | No. of people analysed | No. of people with events | No. of people analysed | P values, RR (95% CI), OR (95% CI) | ||
| Resolution of ear discharge or 'dry ear' at 1 to 2 weeks [Measurement method or definition used: not/unclear if/otoscopically confirmed]1 Time point: [State actual time point] | ||||||
| Resolution of ear discharge or 'dry ear' at 2 to 4 weeks [Measurement method or definition used: not/unclear if/otoscopically confirmed] Time point: [xx] | ||||||
| Resolution of ear discharge or 'dry ear' after 4 weeks [Measurement method or definition used: not/unclear if/otoscopically confirmed] Time point: [xx] | ||||||
| Ear pain/discomfort/local irritation Time point: [xx] | ||||||
| Suspected ototoxicity [Measurement method or definition used] Time point: [xx] | ||||||
| Sensorineural hearing loss [Measurement method or definition used] Time point: [xx] | ||||||
| Tinnitus [Measurement method or definition used] Time point: [xx] | ||||||
| Dizziness/vertigo/balance [Measurement method or definition used] Time point: [xx] | ||||||
| Serious complications: Time point: state length of follow‐up of the trial | Note down the page number/table where info was found for ease of checking | |||||
| Otitic meningitis [How was this diagnosed?] | ||||||
| Lateral sinus thrombosis [How was this diagnosed?] | ||||||
| Cerebellar abscess [How was this diagnosed?] | ||||||
| Mastoid abscess/mastoiditis [How was this diagnosed?] | ||||||
| Postauricular fistula [How was this diagnosed?] | ||||||
| Facial palsy [How was this diagnosed?] | ||||||
| Other complications [How was this diagnosed?] | ||||||
| Death [How was this diagnosed?] | ||||||
| Multiple serious complications [How was this diagnosed?] | ||||||
| Comment/additional notes: If any calculations are needed to arrive at the data above, note this down here. | ||||||
1State briefly how this was measured in the study, especially whether there was deviation from what was expected in the protocol.
For adverse events, note down how these were collected, e.g. whether the adverse event was one of the prespecified events that the study planned to collect, when it was collected and how/who measured it (e.g. as reported by patients, during examination and whether any scoring system was used).
Process for sifting search results and selecting studies for inclusion.
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
Comparison 1: Topical antibiotics versus acetic acid, Outcome 1: Resolution of ear discharge (1 to 2 weeks)
Comparison 1: Topical antibiotics versus acetic acid, Outcome 2: Resolution of ear discharge (2 to 4 weeks)
Comparison 1: Topical antibiotics versus acetic acid, Outcome 3: Ear pain, discomfort, irritation
Comparison 2: Topical antibiotics versus aluminium acetate, Outcome 1: Ototoxicity
Comparison 3: Topical antibiotics versus boric acid, Outcome 1: Resolution of ear discharge (1 to 2 weeks)
Comparison 3: Topical antibiotics versus boric acid, Outcome 2: Resolution of ear discharge (2 to 4 weeks)
Comparison 3: Topical antibiotics versus boric acid, Outcome 3: Ear pain, discomfort, irritation
Comparison 3: Topical antibiotics versus boric acid, Outcome 4: Change in hearing
Comparison 4: Topical antibiotics versus povidone‐iodine, Outcome 1: Resolution of ear discharge (1 to 2 weeks)
Comparison 4: Topical antibiotics versus povidone‐iodine, Outcome 2: Resolution of ear discharge (2 to 4 weeks)
Comparison 5: Topical and systemic antibiotics versus acetic acid, Outcome 1: Resolution of ear discharge (2 to 4 weeks)
Comparison 5: Topical and systemic antibiotics versus acetic acid, Outcome 2: Resolution of ear discharge (after 4 weeks)
| Topical antibiotics compared to acetic acid for chronic suppurative otitis media | |||||||
| Patient or population: chronic suppurative otitis media | |||||||
| Outcomes | Number of participants (studies) | Relative effect | Anticipated absolute effects* (95% CI) | Certainty of the evidence | What happens | ||
|---|---|---|---|---|---|---|---|
| Without topical antibiotics | With topical antibiotics | Difference | |||||
| Resolution of ear discharge (1 to 2 weeks) Aminoglycosides | 100 | RR 0.88 | Study population | ⊕⊝⊝⊝ | It is very uncertain whether acetic acid is more effective at resolving ear discharge compared with topical aminoglycoside antibiotics at 14 days | ||
| 84.0% | 73.9% | 10.1% fewer | |||||
| Resolution of ear discharge (after 4 weeks) ‐ not measured | — | — | — | — | — | — | No study reported this outcome |
| Quality of life ‐ not measured | — | — | — | — | — | — | No study reported this outcome |
| Ear pain, discomfort, irritation | 189 | RR 0.16 | Study population | ⊕⊝⊝⊝ | Acetic acid may cause more ear pain, discomfort and/or irritation than topical antibiotics (aminoglycosides and quinolones) but we are very uncertain about the results | ||
| 5.3% | 0.9% | 4.5% fewer | |||||
| Hearing | 107 | One study reports that "audiometric tests showed no detectable overall, isolated not idiosyncratic hearing loss from any treatment". No numeric results were provided. | very low3 | It is uncertain whether there is a difference in hearing between topical quinolones and topical acetic acid | |||
| Serious complications ‐ not measured | — | — | — | — | — | — | No study reported that any participant died or had any intracranial or extracranial complications |
| Suspected ototoxicity | 100 | One study (100 participants) reported: "… none of the patients had any kind of ear damage or toxicity" | very low4 | It is uncertain if there is a difference in ototoxicity between topical aminoglycosides and topical acetic acid | |||
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | |||||||
| GRADE Working Group grades of evidence | |||||||
| 1Downgraded to very low‐certainty evidence: downgraded by one level due to study limitations (risk of bias) as the study had unclear randomisation, allocation concealment and blinding. Downgraded by one level due to indirectness as the outcome used was 'clinical cure' rather than resolution of ear discharge. Downgraded by one level due to suspected publication bias as one 'unpublished' study was identified indicating the possibility of unreported trials. 3Downgraded to very low‐certainty evidence: downgraded by two levels due to imprecision as no numeric results were provided and the result came from a small study (107 participants). Downgraded by one level due to suspected publication bias as one 'unpublished' study was identified indicating the possibility of unreported trials. 4Downgraded to very low‐certainty evidence: downgraded by one level due to study limitations (risk of bias) as the study had unclear randomisation, allocation concealment and blinding. Downgraded by one level due to imprecision as the result came from a small study (100 participants). Downgraded by one level due to suspected publication bias (one 'unpublished' study identified indicating the possibility of unreported trials). | |||||||
| Topical quinolones compared to boric acid for chronic suppurative otitis media | |||||||
| Patient or population: chronic suppurative otitis media | |||||||
| Outcomes | Number of participants (studies) | Relative effect | Anticipated absolute effects* (95% CI) | Certainty of the evidence | What happens | ||
|---|---|---|---|---|---|---|---|
| Without topical quinolones | With topical quinolones | Difference | |||||
| Resolution of ear discharge (1 to 2 weeks) Quinolones | 411 | RR 1.86 | Study population | ⊕⊕⊕⊝ | Topical quinolones are likely to increase the number of people with resolution of ear discharge at 2 weeks compared with topical boric acid | ||
| 31.9% | 59.3% | 27.4% more | |||||
| Resolution of ear discharge (after 4 weeks) ‐ not measured | — | — | — | — | — | — | No study measured resolution of ear discharge at 4 weeks |
| Quality of life ‐ not measured | — | — | — | — | — | — | No study measured quality of life |
| Ear pain, discomfort, irritation | 510 | RR 0.56 | Study population | ⊕⊕⊝⊝ | Topical quinolones may result in less ear pain, discomfort or irritation at 4 weeks compared to topical boric acid | ||
| 11.8% | 6.6% | 5.2% fewer | |||||
| Average change in hearing from baseline | 390 | — | The mean average change in hearing from baseline without topical quinolones was 2.69 dB | The mean average change in hearing from baseline with topical quinolones was 5.42 dB | MD 2.79 dB higher | ⊕⊕⊝⊝ | Topical quinolones may result in greater improvement in mean hearing from baseline compared with topical boric acid; however this effect size may not be clinically important |
| Serious complications ‐ not measured | — | — | — | — | — | — | No study reported that any participant died or had any intracranial or extracranial complications |
| Suspected ototoxicity ‐ not measured | — | — | — | — | — | — | No study measured this outcome |
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | |||||||
| GRADE Working Group grades of evidence | |||||||
| 1Downgraded by one level to moderate‐certainty evidence due to suspected publication bias. We identified two unpublished studies comparing antibiotics and antiseptics, which indicates that there may be more unpublished studies. | |||||||
| Topical antibiotics compared to povidone‐iodine for chronic suppurative otitis media | |||||||
| Patient or population: chronic suppurative otitis media | |||||||
| Outcomes | Number of participants (studies) | Relative effect | Anticipated absolute effects* (95% CI) | Certainty of the evidence | What happens | ||
|---|---|---|---|---|---|---|---|
| Without topical antibiotics | With topical antibiotics | Difference | |||||
| Resolution of ear discharge (1 to 2 weeks) | 39 | RR 1.02 | Study population | ⊕⊝⊝⊝ | It is uncertain whether there is a difference in the resolution of ear discharge at 2 weeks between topical antibiotics and topical povidone‐iodine | ||
| 88.9% | 90.7% | 1.8% more | |||||
| Resolution of ear discharge (after 4 weeks) ‐ not measured | — | — | — | — | — | — | No study measured this outcome |
| Quality of life ‐ not measured | — | — | — | — | — | — | No study measured this outcome |
| Ear pain, discomfort, irritation ‐ not measured | — | — | — | — | — | — | No study measured this outcome |
| Hearing | 40 (1 RCT) | "There was no deterioration of hearing as assessed by pure tone audiometry" | very low2 | — | |||
| Serious complications ‐ not measured | — | — | — | — | — | — | No study reported that any participant died or had any intracranial or extracranial complications |
| Suspected ototoxicity | 40 | "No patient developed allergic manifestations or ototoxic effects" | very low3 | — | |||
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | |||||||
| GRADE Working Group grades of evidence | |||||||
| 1Downgraded to very low‐certainty evidence. Downgraded by one level due to risk of bias (uncertain randomisation, allocation concealment and possibility of selective reporting). Downgraded by one level due to imprecision (small study size: 39 participants, confidence interval crosses the line of minimally clinical important difference). Downgraded by one level due to suspected publication bias (one study referred to long‐term results that appear to be unpublished and we identified one abstract that appeared to be relevant to this comparison but for which no paper was obtainable). 2Downgraded to very low‐certainty evidence. Downgraded by one level due to risk of bias (uncertain randomisation, allocation concealment and possibility of selective reporting). Downgraded by two levels due to imprecision (no numeric results were presented and very small study size (39 participants)). Downgraded by one level due to suspected publication bias (one study referred to long‐term results, which appear to be unpublished, and we identified one abstract that appeared to be relevant to this comparison but for which no paper was obtainable). 3Downgraded to very low‐certainty evidence. Downgraded by two levels due to risk of bias (uncertain randomisation, allocation concealment and possibility of selective reporting as it is unclear how the outcome was defined). Downgraded by two levels due to imprecision (no numeric results were presented and very small study size (39 participants). Downgraded by one level due to suspected publication bias (one study referred to long‐term results that appear to be unpublished and we identified one abstract that appeared to be relevant to this comparison but for which no paper was obtainable). | |||||||
| Topical antibiotics with steroids | Topical antibiotics | Systemic antibiotics | Topical antiseptics | Aural toileting (ear cleaning) | |
|---|---|---|---|---|---|
| Topical antibiotics with steroids | Review CSOM‐4 | ||||
| Topical antibiotics | Review CSOM‐4 | Review CSOM‐1 | |||
| Systemic antibiotics | Review CSOM‐4 | Review CSOM‐3 | Review CSOM‐2 | ||
| Topical antiseptics | Review CSOM‐4 | Review CSOM‐6 | Review CSOM‐6 | Review CSOM‐5 | |
| Aural toileting | Review CSOM‐4 | Not reviewed | Not reviewed | Not reviewed | Review CSOM‐7 |
| Placebo (or no intervention) | Review CSOM‐4 | Review CSOM‐1 | Review CSOM‐2 | Review CSOM‐5 | Review CSOM‐7 |
| CSOM‐1: Topical antibiotics for chronic suppurative otitis media (Brennan‐Jones 2018a). CSOM‐2: Systemic antibiotics for chronic suppurative otitis media (Chong 2018a). CSOM‐3: Topical versus systemic antibiotics for chronic suppurative otitis media (Chong 2018b). CSOM‐4: Topical antibiotics with steroids for chronic suppurative otitis media (Brennan‐Jones 2018b). CSOM‐5: Topical antiseptics for chronic suppurative otitis media (Head 2018a). CSOM‐6: Antibiotics versus topical antiseptics for chronic suppurative otitis media (Head 2018b). CSOM‐7: Aural toilet (ear cleaning) for chronic suppurative otitis media (Bhutta 2018). | |||||
| Class of antibiotics | Examples | Route of administration |
|---|---|---|
| Quinolones | Ciprofloxacin, ofloxacin, levofloxacin | Oral, intravenous, topical |
| Aminoglycosides | Gentamicin, tobramycin | Topical or parenteral |
| Neomycin/framycetin | Only topical | |
| Cephalosporins | Ceftazidime | Parenteral |
| Penicillins | Ticarcillin plus clavulanic acid | Parenteral |
| Monobactams | Aztreonam | Parenteral |
| Antiseptic agent used aurally | Target and mechanism of action |
|---|---|
| Rubbing alcohol (ethanol, isopropanol) | Penetrating agents that cause loss of cellular membrane function, leading to release of intracellular components, denaturing of proteins, and inhibition of DNA, RNA, protein and peptidoglycan synthesis. |
| Povidone‐iodine | Highly active oxidising agents that destroy cellular activity of proteins. Disrupts oxidative phosphorylation and membrane‐associated activities. Iodine reacts with cysteine and methionine thiol groups, nucleotides and fatty acids, resulting in cell death. |
| Chlorhexidine | Membrane‐active agents that damage cell wall and outer membrane, resulting in collapse of membrane potential and intracellular leakage. Enhanced passive diffusion mediates further uptake, causing coagulation of cytosol. |
| Hydrogen peroxide | Produces hydroxyl free radicals that function as oxidants, which react with lipids, proteins and DNA. Sulfhydryl groups and double bonds are targeted in particular, thus increasing cell permeability. |
| Boric acid | It is likely that the change in the pH media of the ear canal interrupts the growth of bacteria by affecting the amino acid, which causes alteration in the three‐dimensional structure of bacterial enzymes. Extreme changes in pH cause protein denaturation. |
| Aluminium acetate/acetic acid | Acetic acid changes the pH media of the ear canal and interrupts the growth of bacteria by affecting the amino acid, which causes alteration in the three‐dimensional structure of bacterial enzymes. Extreme changes in pH cause protein denaturation. Aluminium acetate is an astringent that helps reduce itching, stinging and inflammation. |
| Sources: Gupta 2015; McDonnell 1999; Sheldon 2005. | |
| Ref ID (no. participants) | Setting | Population | Antibiotic | Topical antiseptic | Treatment | Follow‐up | Background treatment | Notes |
|---|---|---|---|---|---|---|---|---|
| Topical antibiotics versus acetic acid | ||||||||
| (159 participants) | South Africa, city (secondary care) | Patients with otorrhoea because of active mucosal COM Age over 6 years (90% between 20 and 34 years) | Ciprofloxacin, ear drops, (no concentration), 6 drops/8 hours | 1% acetic acid 6 drops/12 hours | 4 weeks | Up to 8 weeks | Aural cleaning at 1st visit | Part of a 3‐arm trial; third arm used boric acid (see below) |
| (58 participants in relevant arms) | Malawi (community setting) | CSOM (no details) "Children" ‐ no age information provided | 0.3% ofloxacin 3 drops/8 hours | 2% acetic acid in spirit 25% and glycerine 30% 3 drops/8 hours | 2 weeks | 8 weeks | Suction cleaning at the start of trial, at 1‐week and 2‐week follow‐up | Part of a 3‐arm trial; third arm used topical antiseptics + steroids |
| Neomycin 0.5%/polymixin B 0.1%, 3 drops/8 hours | ||||||||
| (100 participants) | India (secondary care) | Tubotympanic (safe) type of CSOM Mean age 69 years (range: 10 to 60 years) | Gentamicin (0.3%), ear drops, 3 drops every 8 hours | Acetic acid (1.5%), ear drops, 3 drops every 8 hours | 2 weeks | 2 weeks | None listed | Resolution of ear discharge measured as symptom score |
| Topical antibiotics versus aluminium acetate (Burow's solution) | ||||||||
| (51 participants, 60 ears) | Israel (ENT outpatient clinic) | Chronic otitis media Mean: 44.4 years (range 18 to 73 years) | Ciprofloxacin (no concentration), 15 drops per day | 1% aluminium acetate solution 5 drops/8 hours | 3 weeks | 3 weeks | None mentioned | Randomisation by ear Not possible to use results 3‐arm trial |
| Tobramycin (no concentration), 15 drops per day | ||||||||
| Topical antibiotics versus boric acid | ||||||||
| (159 participants) | South Africa, city (secondary care) | Patients with otorrhoea because of active mucosal COM Age over 6 years (90% between 20 and 34 years) | Ciprofloxacin, ear drops, (no concentration), 6 drops/8 hours | Boric acid powder Single administration | 4 weeks (antibiotics) | Up to 8 weeks | Aural cleaning at 1st visit | Part of a 3‐arm trial; third arm used acetic acid (see above) |
| Macfadyen 2005 (427 participants) | Kenya, rural (community, school setting) | Children (aged over 5 years) with CSOM Mean age 11.1 ± 3.15 years | 0.3% ciprofloxacin, ear drops, no volume given every 12 hours | 2% boric acid in 45% alcohol, ear drops, no volume given every 12 hours | School days only for 2 weeks | 4 weeks | Daily dry mopping before application | — |
| Topical antibiotics versus povidone‐iodine | ||||||||
| Jaya 2003 (40 participants) | India, city (ENT outpatient clinic) | Actively discharging CSOM with moderate to large central perforation Age over 10 years (50% between 21 to 21 to 40) | Ciprofloxacin 0.3% ear drops, 3 drops 3 times daily | Povidone‐iodine 5% solution, 3 drops 3 times daily | 10 days | 4 weeks | Suction cleaning before trial and then daily dry mopping | — |
| Systemic and topical antibiotics versus acetic acid and aural toileting | ||||||||
| (100 participants) | India (secondary care) | CSOM Mean age: 36.4 years (range: 6 to 72 years) | Topical ciprofloxacin (no concentration/volume) daily for 3 months, plus oral ciprofloxacin, 500 mg twice daily for 15 days | Diluted acetic acid (2 mL) daily. Every second day this was completed at the hospital with suction ear cleaning. Continued until no further discharge | See details for each treatment arm | 3 months | Dry mopping at 1st visit | — |
| Reference | Unit of randomisation | Discharge results reported by | Definition | Otoscopically confirmed? | Time points | Notes |
|---|---|---|---|---|---|---|
| Ear | Ear | "Clinical success" defined as cessation of otorrhoea and eradication of the micro‐organisms in the post‐treatment culture | Unclear | 2 to 4 weeks: 21 days | Not possible to use these results as randomisation by ear (9/51 patients had bilateral disease) | |
| Person | Person | "Absence of discharge" | Otoscopically confirmed | 2 to 4 weeks: 15 days After 4 weeks: 1 month | — | |
| Person | Person | "Inactive" ear | Microscopic examination | 1 to 2 weeks: 2 weeks 2 to 4 weeks: 4 weeks | — | |
| Person | Person | "Inactive" ear (dry) | Otoscopically confirmed | 2 to 4 weeks: 4 weeks | Also measured patient satisfaction, which asked patients whether their ears were 'completely dry', 'better but not completely dry', 'no better, still running' | |
| Person | Both by person | Resolution of aural discharge | Otoscopically confirmed | 1 to 2 weeks: 2 weeks 2 to 4 weeks: 4 weeks | For bilateral disease results were reported for when either ear was dry and when both ears were dry. For this review we have used the 'both ears' results. | |
| Unclear | Results reported by ear | "Dry ear" | Unclear | 1 to 2 weeks: 1 week 2 to 4 weeks: 2 weeks | Results not used as it was not possible to account for correlation between ears due to bilateral disease | |
| Person | Person | "Clinical cure" defined as a score of < 3 on a symptom scale1 | Unclear | 1 to 2 weeks: 14 days | — | |
| 1Symptom scale; tinnitus: absent (0), mild (1), moderate (2), severe (3); amount of discharge: absent (0), mild (1), moderate (2), severe (3); type of discharge: absent (0), mucoid (1), mucopurulent (2), purulent (3). Sum scores in each category to give range of 0 to 9. | ||||||
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1.1 Resolution of ear discharge (1 to 2 weeks) Show forest plot | 1 | Risk Ratio (M‐H, Random, 95% CI) | Subtotals only | |
| 1.1.1 Aminoglycosides | 1 | 100 | Risk Ratio (M‐H, Random, 95% CI) | 0.88 [0.72, 1.08] |
| 1.2 Resolution of ear discharge (2 to 4 weeks) Show forest plot | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Subtotals only | |
| 1.2.1 Quinolone vs acetic acid | 1 | 89 | Risk Ratio (M‐H, Fixed, 95% CI) | 2.93 [1.71, 5.04] |
| 1.3 Ear pain, discomfort, irritation Show forest plot | 2 | 189 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.16 [0.02, 1.34] |
| 1.3.1 Quinolones | 1 | 89 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.11 [0.01, 1.96] |
| 1.3.2 Aminoglycosides | 1 | 100 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.33 [0.01, 7.99] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 2.1 Ototoxicity Show forest plot | 1 | 40 | Risk Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 3.1 Resolution of ear discharge (1 to 2 weeks) Show forest plot | 1 | Risk Ratio (M‐H, Random, 95% CI) | Subtotals only | |
| 3.1.1 Quinolones | 1 | 411 | Risk Ratio (M‐H, Random, 95% CI) | 1.86 [1.48, 2.35] |
| 3.2 Resolution of ear discharge (2 to 4 weeks) Show forest plot | 2 | Risk Ratio (M‐H, Random, 95% CI) | Subtotals only | |
| 3.2.1 Quinolones | 2 | 488 | Risk Ratio (M‐H, Random, 95% CI) | 1.27 [1.07, 1.49] |
| 3.3 Ear pain, discomfort, irritation Show forest plot | 2 | 510 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.56 [0.32, 0.98] |
| 3.3.1 Quinolones | 2 | 510 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.56 [0.32, 0.98] |
| 3.4 Change in hearing Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| 3.4.1 Quinolone | 1 | 390 | Mean Difference (IV, Fixed, 95% CI) | 2.79 [0.48, 5.10] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 4.1 Resolution of ear discharge (1 to 2 weeks) Show forest plot | 1 | Risk Ratio (M‐H, Random, 95% CI) | Subtotals only | |
| 4.1.1 Quinolones | 1 | 39 | Risk Ratio (M‐H, Random, 95% CI) | 1.02 [0.82, 1.26] |
| 4.2 Resolution of ear discharge (2 to 4 weeks) Show forest plot | 1 | Risk Ratio (M‐H, Random, 95% CI) | Subtotals only | |
| 4.2.1 Quinolone | 1 | 36 | Risk Ratio (M‐H, Random, 95% CI) | 1.03 [0.81, 1.30] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 5.1 Resolution of ear discharge (2 to 4 weeks) Show forest plot | 1 | Risk Ratio (M‐H, Random, 95% CI) | Subtotals only | |
| 5.1.1 Quinolone | 1 | 100 | Risk Ratio (M‐H, Random, 95% CI) | 0.61 [0.40, 0.93] |
| 5.2 Resolution of ear discharge (after 4 weeks) Show forest plot | 1 | 100 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.69 [0.53, 0.90] |
| 5.2.1 Quinolone | 1 | 100 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.69 [0.53, 0.90] |
