Topical Ciprofloxacin vs Intramuscular Gentamicin for Chronic Otitis Media
Silvano Esposito, MD; Silvana Noviello, PhD; Gioacchino D'Errico, MD; Carmine Montanaro, MD \s=b\ Clinical and bacteriological efficacy of topical ciprofloxacin hydrochloride was compared with that of intramuscular gentamicin sulfate in two groups composed of 30 patients each, all of whom were affected by chronic otitis media in the acute stage. Antibiotics were randomly given for 5 to 10 days according to the following schedules: ciprofloxacin hydrochloride, four drops (250 mg/mL in saline solution) administered locally twice a day, or gentamicin sulfate, 80 mg administered intramuscularly twice a day. We admitted to the study only adult patients affected by chronic otitis media in the acute stage with perforation of the tympanic membrane, without cholesteatoma, whose bacteriological culture was positive for Pseudomonas susceptible in vitro to ciprofloxacin and gentamicin. The clinical and bacteriological response was stated 12 hours after the interruption of the treatment, and 2 and 3 weeks later (follow-up). A favorable clinical result was observed in 26 (87%) of 30 patients under ciprofloxacin treatment; in 30 patients receiving gentamicin, a favorable clinical response was observed in 20 (66%) and bacteriological eradication in 13 (43%). No relapse at the follow-up was observed. Topical ciprofloxacin seems to be more effective than intramuscular gentamicin in curing Pseudomonas-caused chronic otitis media in the acute stage. (Arch Otolaryngol Head Neck Surg. 1992;118:842-844)
varying degrees, gram-positive and gram-negative well anaerobic bacteria aerobic To frequently of otitis media.1"4 involved in the as
as
are
suppurative Pseudomonas detection, for example, is reported in differ¬ ent years from different authors in a percentage ranging between 19% and 69%.5"7 Our experience suggested that, during the last 2 years, Pseudomonas aeruginosa was re¬ sponsible for purulent otorrhea in 102 (44%) of 233 patients cause
affected by chronic otitis media in the acute stage. The frequent detection of Pseudomonas and other multi-
Accepted
for publication October 17, 1991. From the Institutes of Infectious Diseases (Drs Esposito and Noviello) and Otolaryngology (Drs D'Errico and Montanaro), University of Naples (Italy), Ospedale Ges\l=u`\e Maria. Presented as a poster exhibit at the Interscience Conference on Anti-
microbial Agents and 1989.
Reprint requests to
Chemotherapy, Houston, Tex, September 19,
Institute of Infectious
Diseases, University of Na-
ples, Ospedale Ges\l=u`\e Maria, Via D Cotugno 1, 80135 Naples, Italy (Dr Esposito).
ply resistant bacteria as well as the possible low concen¬ tration of antibiotics at this site are probably responsible for the frequent failure following empirical therapies per¬ formed with conventional antibacterial agents. The epide¬ miologica! character of suppurative otitis might suggest
the use of antibiotics that also include Pseudomonas in their antibacterial spectra, such as aminoglycosides. In fact, many otologists successfully utilize these antibiotics in drop form for patients with perforation and drainage of the tympanic membrane. Unfortunately, the bacteriological examination of middle ear effusion is not performed in general practice, and antibiotics usually chosen for therapy exclude Pseudomonas in their antibacterial spectra. The aim of this study was to evaluate the therapeutic efficacy and tolerability of topical ciprofloxacin hydrochloride, which is
particularly active nontoxic drug against Pseudomonas, vs gentamicin sulfate given intramuscularly for treatment of a
chronic otitis media in the acute stage.
PATIENTS AND METHODS
Antibacterial
Drugs
was prepared by dissolving the pure Ciprofloxacin sterile ciprofloxacin powder in saline solution to obtain the final concentration of 250 mg/mL. Preliminary tests were performed by an agar diffusion method to evaluate any possible loss of ac¬ tivity of the solution stored either in the refrigerator or at room temperature. These tests were carried out for 10 days and did not show any decrease in the in vitro antibacterial activity of the drug. We used 80-mg intramuscular injectable vials of gentamicin
solution
sulfate.
Patients Sixty adult patients (27 men, 33 women) affected by chronic
suppurative otitis were included in this study. Data concerning the patients' demographic characteristics are reported in Table 1. All patients were affected by mild or moderate otitis media in the acute stage with perforation of the tympanic membrane and without choiesteatoma or mastoiditis. Diagnosis was stated according to the following criteria: the otitis media had lasted at
least 3 years, purulent otorrhea had recurred at least once annu¬ ally, and recurrent episodes of purulent otorrhea had been con¬ stant for at least 15 days. Pregnant women, patients with a history of allergy to quinolones or aminoglycosides, and patients younger than 18 years old were excluded. All patients had given their informed consent be¬ fore entering the study. No patient had underlying diseases such as diabetes; none was receiving any other drug during the study. Many patients (40 of 60) had been receiving different antibiotics
Downloaded From: http://archotol.jamanetwork.com/ by a Western University User on 06/08/2015
Table
Table 2.—Prior
1.—Demographic Characteristics Sex
Age,
-1 M F
Gentamicin sulfatetreated group
13
17
42
Cephalosporins Lincomycin
Range
treated group Total
14
16
36
18-56
27
33
39
18-65
Table
group
4.—Bacteriological Response,
5
Results,
40
No. (%)
Improvement
Failure
30
13(43)
30
25 (83)
7(24) 1 (4)
10(33) 4 (13)
No. (%)
Ciprofloxacin hydrochloridetreated group
30
13(43)
27(57)
30
25 (85)
5 (17)
for systemic or local effect at appropriate dosages. The duration of prior therapies had been 5 to 10 days. Previous therapy had been interrupted 1 to 7 days before admission to the study, as no significant improvement of the subjective symptoms had been noticed (Table 2).
Antibiotic Treatment
Ciprofloxacin was randomly given according to the following schedules: group A (30 patients) received four drops containing 250 mg/mL of ciprofloxacin hydrochloride in saline solution, given locally twice a day; group (30 patients) received 80 mg of gentamicin sulfate intramuscularly twice a day according to the manufacturer's dosing suggestions. All bacteria were identified by the API system (Bioherieux Ita¬ lia, Rome, Italy). Susceptibility to ciprofloxacin and gentamicin was always established by a microdilution broth method. Treatments were carried out for at least 5 days. Patients who were not cured after this period of therapy continued the treat¬ ment until cured, or in any case not longer than 10 days. The clin¬ ical and bacteriological evaluation was stated 12 hours and 14 and 21 days (follow-up) after the interruption of treatment. Patient Examination Patients were clinically examined by otoscopy before, during (every 2 to 3 days), and after the end of the therapy, and a thor¬ ough inquiry for any side effects was carried out at each clinical examination. Audiometrie measurement and vestibular tests were done before starting the therapy and 24 hours after the end of the therapy. Aerobic cultures of the middle ear effusion were always performed before starting therapy and, if the secretion was still present, again at each clinical examination. Anaerobic cultures were
not
performed.
Statistical
Analysis
2 compare the percentages of clinical and bacteriological responses in the two groups of patients examined to evaluate a possible statistical difference. We calculated
to
10
Cure
No. of Patients Eradication Persistence Gentamicin sulfatetreated group
9
(local drops)
Others* Total
No. of Patients
Ciprofloxacin hydrochloride-treated
3
(67%) *Gentamicin, netilmicin, macrolides, and trimethoprimsulfamethizole.
Table 3.—Clinical Gentamicin sulfate-treated group
13
Amoxicillin
18-65
Neomycin/polymyxin
Ciprofloxacin hydrochloride-
No. of Patients
Antibiotics
y
-1
Mean
Therapies
RESULTS
Clinical and bacteriological responses are reported in Tables 3 and 4, respectively. In group B, receiving genta¬ micin treatment, 67% of the patients had a favorable clin¬ ical response, and in 33% of patients no significant clinical improvement was noted. These results reflect a high per¬ centage of bacteriological persistence (57%). In group A, receiving local drops of ciprofloxacin, we observed clinical remission in 83% of patients and improvement in 4% (one patient). The patient who clinically improved still had a slight secretion from the ear, which was still infected by
aeruginosa.
Bacterial cultures of the middle ear effusion were performed 12 hours after the interruption of the therapy, and no ciprofloxacin or gentamicin resistance was detected in bacteria still present at the end of the treatment. In all patients who were clinically and bacteriologically cured 12 hours after the interruption of the treatment, we confirmed their clinical status 14 and 21 days after the end of the
therapy (follow-up).
No side effect was recorded for any patient, and no worsening of the audiometrie function related to local or parenteral therapy was observed. The bacteriological and clinical cure rates observed in group A were statistically higher than in group (P
Silvano Esposito, MD; Silvana Noviello, PhD; Gioacchino D'Errico, MD; Carmine Montanaro, MD \s=b\ Clinical and bacteriological efficacy of topical ciprofloxacin hydrochloride was compared with that of intramuscular gentamicin sulfate in two groups composed of 30 patients each, all of whom were affected by chronic otitis media in the acute stage. Antibiotics were randomly given for 5 to 10 days according to the following schedules: ciprofloxacin hydrochloride, four drops (250 mg/mL in saline solution) administered locally twice a day, or gentamicin sulfate, 80 mg administered intramuscularly twice a day. We admitted to the study only adult patients affected by chronic otitis media in the acute stage with perforation of the tympanic membrane, without cholesteatoma, whose bacteriological culture was positive for Pseudomonas susceptible in vitro to ciprofloxacin and gentamicin. The clinical and bacteriological response was stated 12 hours after the interruption of the treatment, and 2 and 3 weeks later (follow-up). A favorable clinical result was observed in 26 (87%) of 30 patients under ciprofloxacin treatment; in 30 patients receiving gentamicin, a favorable clinical response was observed in 20 (66%) and bacteriological eradication in 13 (43%). No relapse at the follow-up was observed. Topical ciprofloxacin seems to be more effective than intramuscular gentamicin in curing Pseudomonas-caused chronic otitis media in the acute stage. (Arch Otolaryngol Head Neck Surg. 1992;118:842-844)
varying degrees, gram-positive and gram-negative well anaerobic bacteria aerobic To frequently of otitis media.1"4 involved in the as
as
are
suppurative Pseudomonas detection, for example, is reported in differ¬ ent years from different authors in a percentage ranging between 19% and 69%.5"7 Our experience suggested that, during the last 2 years, Pseudomonas aeruginosa was re¬ sponsible for purulent otorrhea in 102 (44%) of 233 patients cause
affected by chronic otitis media in the acute stage. The frequent detection of Pseudomonas and other multi-
Accepted
for publication October 17, 1991. From the Institutes of Infectious Diseases (Drs Esposito and Noviello) and Otolaryngology (Drs D'Errico and Montanaro), University of Naples (Italy), Ospedale Ges\l=u`\e Maria. Presented as a poster exhibit at the Interscience Conference on Anti-
microbial Agents and 1989.
Reprint requests to
Chemotherapy, Houston, Tex, September 19,
Institute of Infectious
Diseases, University of Na-
ples, Ospedale Ges\l=u`\e Maria, Via D Cotugno 1, 80135 Naples, Italy (Dr Esposito).
ply resistant bacteria as well as the possible low concen¬ tration of antibiotics at this site are probably responsible for the frequent failure following empirical therapies per¬ formed with conventional antibacterial agents. The epide¬ miologica! character of suppurative otitis might suggest
the use of antibiotics that also include Pseudomonas in their antibacterial spectra, such as aminoglycosides. In fact, many otologists successfully utilize these antibiotics in drop form for patients with perforation and drainage of the tympanic membrane. Unfortunately, the bacteriological examination of middle ear effusion is not performed in general practice, and antibiotics usually chosen for therapy exclude Pseudomonas in their antibacterial spectra. The aim of this study was to evaluate the therapeutic efficacy and tolerability of topical ciprofloxacin hydrochloride, which is
particularly active nontoxic drug against Pseudomonas, vs gentamicin sulfate given intramuscularly for treatment of a
chronic otitis media in the acute stage.
PATIENTS AND METHODS
Antibacterial
Drugs
was prepared by dissolving the pure Ciprofloxacin sterile ciprofloxacin powder in saline solution to obtain the final concentration of 250 mg/mL. Preliminary tests were performed by an agar diffusion method to evaluate any possible loss of ac¬ tivity of the solution stored either in the refrigerator or at room temperature. These tests were carried out for 10 days and did not show any decrease in the in vitro antibacterial activity of the drug. We used 80-mg intramuscular injectable vials of gentamicin
solution
sulfate.
Patients Sixty adult patients (27 men, 33 women) affected by chronic
suppurative otitis were included in this study. Data concerning the patients' demographic characteristics are reported in Table 1. All patients were affected by mild or moderate otitis media in the acute stage with perforation of the tympanic membrane and without choiesteatoma or mastoiditis. Diagnosis was stated according to the following criteria: the otitis media had lasted at
least 3 years, purulent otorrhea had recurred at least once annu¬ ally, and recurrent episodes of purulent otorrhea had been con¬ stant for at least 15 days. Pregnant women, patients with a history of allergy to quinolones or aminoglycosides, and patients younger than 18 years old were excluded. All patients had given their informed consent be¬ fore entering the study. No patient had underlying diseases such as diabetes; none was receiving any other drug during the study. Many patients (40 of 60) had been receiving different antibiotics
Downloaded From: http://archotol.jamanetwork.com/ by a Western University User on 06/08/2015
Table
Table 2.—Prior
1.—Demographic Characteristics Sex
Age,
-1 M F
Gentamicin sulfatetreated group
13
17
42
Cephalosporins Lincomycin
Range
treated group Total
14
16
36
18-56
27
33
39
18-65
Table
group
4.—Bacteriological Response,
5
Results,
40
No. (%)
Improvement
Failure
30
13(43)
30
25 (83)
7(24) 1 (4)
10(33) 4 (13)
No. (%)
Ciprofloxacin hydrochloridetreated group
30
13(43)
27(57)
30
25 (85)
5 (17)
for systemic or local effect at appropriate dosages. The duration of prior therapies had been 5 to 10 days. Previous therapy had been interrupted 1 to 7 days before admission to the study, as no significant improvement of the subjective symptoms had been noticed (Table 2).
Antibiotic Treatment
Ciprofloxacin was randomly given according to the following schedules: group A (30 patients) received four drops containing 250 mg/mL of ciprofloxacin hydrochloride in saline solution, given locally twice a day; group (30 patients) received 80 mg of gentamicin sulfate intramuscularly twice a day according to the manufacturer's dosing suggestions. All bacteria were identified by the API system (Bioherieux Ita¬ lia, Rome, Italy). Susceptibility to ciprofloxacin and gentamicin was always established by a microdilution broth method. Treatments were carried out for at least 5 days. Patients who were not cured after this period of therapy continued the treat¬ ment until cured, or in any case not longer than 10 days. The clin¬ ical and bacteriological evaluation was stated 12 hours and 14 and 21 days (follow-up) after the interruption of treatment. Patient Examination Patients were clinically examined by otoscopy before, during (every 2 to 3 days), and after the end of the therapy, and a thor¬ ough inquiry for any side effects was carried out at each clinical examination. Audiometrie measurement and vestibular tests were done before starting the therapy and 24 hours after the end of the therapy. Aerobic cultures of the middle ear effusion were always performed before starting therapy and, if the secretion was still present, again at each clinical examination. Anaerobic cultures were
not
performed.
Statistical
Analysis
2 compare the percentages of clinical and bacteriological responses in the two groups of patients examined to evaluate a possible statistical difference. We calculated
to
10
Cure
No. of Patients Eradication Persistence Gentamicin sulfatetreated group
9
(local drops)
Others* Total
No. of Patients
Ciprofloxacin hydrochloride-treated
3
(67%) *Gentamicin, netilmicin, macrolides, and trimethoprimsulfamethizole.
Table 3.—Clinical Gentamicin sulfate-treated group
13
Amoxicillin
18-65
Neomycin/polymyxin
Ciprofloxacin hydrochloride-
No. of Patients
Antibiotics
y
-1
Mean
Therapies
RESULTS
Clinical and bacteriological responses are reported in Tables 3 and 4, respectively. In group B, receiving genta¬ micin treatment, 67% of the patients had a favorable clin¬ ical response, and in 33% of patients no significant clinical improvement was noted. These results reflect a high per¬ centage of bacteriological persistence (57%). In group A, receiving local drops of ciprofloxacin, we observed clinical remission in 83% of patients and improvement in 4% (one patient). The patient who clinically improved still had a slight secretion from the ear, which was still infected by
aeruginosa.
Bacterial cultures of the middle ear effusion were performed 12 hours after the interruption of the therapy, and no ciprofloxacin or gentamicin resistance was detected in bacteria still present at the end of the treatment. In all patients who were clinically and bacteriologically cured 12 hours after the interruption of the treatment, we confirmed their clinical status 14 and 21 days after the end of the
therapy (follow-up).
No side effect was recorded for any patient, and no worsening of the audiometrie function related to local or parenteral therapy was observed. The bacteriological and clinical cure rates observed in group A were statistically higher than in group (P
