Journal of Chemotherapy
ISSN: 1120-009X (Print) 1973-9478 (Online) Journal homepage: http://www.tandfonline.com/loi/yjoc20
Oral Ciprofloxacin for Treatment of Acute Bacterial Pharyngotonsillitis S. Esposito, G. D’Errico & C. Montanaro To cite this article: S. Esposito, G. D’Errico & C. Montanaro (1990) Oral Ciprofloxacin for Treatment of Acute Bacterial Pharyngotonsillitis, Journal of Chemotherapy, 2:2, 108-112, DOI: 10.1080/1120009X.1990.11738992 To link to this article: http://dx.doi.org/10.1080/1120009X.1990.11738992
Published online: 14 Jul 2016.
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Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=yjoc20 Download by: [Monash University Library]
Date: 17 November 2016, At: 22:44
Journal of Chemotherapy
Oral Ciprofloxacin for Treatment of Acute Bacterial Pharyngotonsillitis S. ESPOSITO - G. D'ERRICO * C. MONTANARO *
Summary -------------------------------The clinical efficacy and tolerability of ciprofloxacin orally administered at the dosage of 250 mg twice a day was evaluated in 25 patients affected by acute bacterial pharyngotonsillitis_ All patients were non-responders to previous conventional antibiotic therapies due to in vitro resistance of the responsible bacteria, or possibly the low antibiotic concentration at the infection site. None of the patients had infections caused by group A ~-haemolyticus streptococcus_ Treatment with ciprof10xacin lasted for 5 -1 0 days (mean 6 _7). A favorable clinical response was observed in 92% of patients (15 resolutions and 7 improvements) at the end of the therapy and two weeks later (follow-up). One patient was not evaluable because of the unfortunate onset of glossitis that caused the interruption of the treatment. No other side-effects were recorded in the other 24 patients. The bacteriological response was excellent: 83% bacteriological eradication, 13% persistence and superinfection in only one patient (4%). Ciprofloxacin administered orally at low dosages is highly effective in the treatment of bacterial pharyngotonsillitis and is also well tolerated. Key words: ciprofloxacin, pharyngotonsillitis, quinolones, tonsillitis.
Clinic of Infectious Diseases, First Medical School, University of Naples, Italy. * Clinic of Otorhinolaryngology, First Medical School, University of Naples, Italy. Address: Dr. Silvano Esposito, Clinica Malattie Infettive, (Ospedale Gesu e Maria), Via D. Cotugno 1 - 80135 Naples, Italy. © Edizioni Riviste Scientifiche - Firenze
Vol. 2 - n. 2 (108-112) - 1990
INTRODUCTION
Acute bacterial pharyngotonsillitis usually has a viral etiology. Nevertheless, bacterial pharyngotonsillitis is not infrequently observed in both pediatric and adult patients 1,2. B-haemolyticus group A streptococcus is certainly the most important and frequent patho-' gen responsible for these infections, especially in childhood, but also other microorganisms which are usually present at the pharyngotonsillar site, such as Staphylococcus aureus, Streptococcus viridans, Streptococcus pneumoniae, Haemophilus, Neiserria, Pseudomonas and Enterobacteria, are occasionally considered as responsible pathogens even in non-immuncompromised hosts. It is still not easy to differentiate between bacterial and viral pharyngotonsillitis, both by clinical and bacteriological examination. Cipro£1oxacin is a new £1uoroquinolone which possesses very high in vitro activity against most of the above mentioned pathogens and penetrates the tonsillar tissue well. Mori et al found a concentration of 1.24 Jlg/g in the tonsillar tissue one hour after the administration of a single 200 mg oral dose. We determined in another study that two hours after the administration of a single oral 250 mg dose, the concentration of cipro£1oxacin in the tonsillar tissue was 2.4 Jlg/mg 3-5. These concentrations are equal to or higher than the serum concentrations and greatly exceed the minimal inhibitory concentrations of cipro£1ocacin against the above mentioned pathogens 6,7 In spite of the good pharmacokinetic data concerning the penetration of cipro£1oxacin into ISSN 1120-009X
ORAL CIPROFLOXACIN FOR TREATMENT OF ACUTE BACTERIAL PHARYNGOTONSll..UTIS
the tonsils, few data are available so far concerning the treatment of bacterial pharyngotonsillitis with low dosages of ciprofloxacin so its efficacy at this dosage has not yet been well determined. The aim of the present study was to evaluate the clinical efficacy and tolerability of a low dose regimen of ciprofloxacin given orally in the treatment of acute bacterial pharyngotonsillitis.
MATERIAL AND METHODS
Twenty-five adult patients (14 males and 11 females) aged between 22 and 70 years (average 40 years) with acute pharyngotonsillitis were admitted to a non-comparative, prospective clillical study (see Table 1). TABLE
1 - Characteristics of the patients No. patients
14*
Males Females Age (mean) 40 years
11
* One patient not evaluable
The clinical diagnosis was done according to the following clinical signs and symptoms: mucositis (100%), tonsillar exudate (100%), fever (32%), dysphagia (60%), and satellite adenopathy (48%). All patients had been taking other conventional antimicrobial drugs in the previous week for at ~east four days at standard dose regimens without significant improvement in the subjective symptoms (Table 2).
TABLE
2 - Previous antibiotic treatments No. pts
Ampicillin Amoxicillin Cefuroxime Lincomycin Miocamicin Gentamicin
4 5 5 4 2
5
Dosages
1g 1g 1g
X X X
2 p.o. 2 p.o. 2 Lm.
600 mg X 2 Lm. 150 mg X 2 p.o. 80 mg X 2 Lm.
109
The reason for the failures of the previous therapies was probably the resistance that we detected in vitro in some responsible bacteria to the antibiotics utilized during prior treatment; or possibly the low concentrations of the drug at the site of infection. Pregnancy, age under 18 years and history of hypersensitivity or allergy to quinolone derivatives, and impaired renal function were criteria for exclusion of the patients from the study. All patients gave their informed consent after the nature of the procedures had been fully explained. No patient was affected by diabetes and/or other underlying diseases. Ciprofloxacin was given orally at a dosage of 250 mg twice a day for 5-10 days (average 6.7 days). Ciprofloxacin was kindly provided by Bayer Italia Spa, Milan, Italy. The clinical responses were stated according to the improvement or disappearance of the above mentioned signs; the bacteriological responses according to the eradication or persistence, at the end of therapy, of bacteria considered responsible. The bacteriological culture of tonsillar exudate, frequently obtained by tonsillar squeezing, was performed before each therapy and, if exudate was still present, during and after the end of treatment. All the responsible bacteria were investigated for their susceptibility to ciprofloxacin and other conventional antibiotics by determining the minimal inhibitory concentrations (MIC) by a microdilution broth method. The breakpoint for ciprofloxacin susceptibility was considered 2
Jlg/rn1. The clinical signs of the infection were examined and noted every 2-3 days during the treatment. Clinical and microbiological followup of the patients cured at the end of the therapy was done two weeks later. Possible adverse reactions and side-effects were carefully researched by inquiry. Clinical examination was carried out two weeks after the end of the therapy (follow-up). The main blood biochemical tests (urea, glucose, creatinine, SGOT, SGPT, Alp, bilirubin, ESR, RBC, WBC, hemoglobin, platelets, total proteins and urinalysis) were performed before the beginning and after the end of each therapy. These data were successively evaluated and compared by Student's «t» test.
TABLE
No.
Age (years)
Sex
Gram Staina
1
46
F
Gram - rods
2
67
F
Gram
3
34
M
Gram
4
28
M
5
48
M
6
20
M
+
cocci
+ rods Gram + cocci Gram + cocci Gram + cocci + +
3 - Clinical, microbiological and demographic data of the patients. MIca (llg/mI)
Response
Culturea Results
Prior Therapy
P. aerugin
Ampicillin
5
8
0.25
Improvement
Persistence
S. aureus + S. marcesc
Amoxicillin
5
4 1
1.0 0.5
Resolution
Eradication
P. vulgaris
Amoxicillin
6
32
0.5
Resolution
Superinfection
S. aureus
Ampicillin
6
16
0.25
Resolution
Eradication
Streptococ.
Gentamicin
7
8
0.003
Resolution
Eradication
S. aureus + P. aerugin
Lincomycin
4
4
2.0 1.0
Improvement
Eradication
>32
Duration (days)
Prior drug
Ciprofloxacin
Clinical
Bacteriological
cocci
S. aureus
Miocamicin
7
16
0.5
Improvement
Persistence
cocci
S. aureus
Gentamicin
5
8
1.0
Resolution
Eradication
Gram - rods
P. aerugin
Gentamicin
7
8
0.015
Improvement
Eradication
Gram - rods
P. aerugin.
Amoxicillin
6
>32
0.5
Resolution
Eradication
S. aureus
Ampicillin
5
>32
0.5
Resolution
Eradication
Streptococ.
Miocamicin
4
2
1.0
Resolution
Eradication
P. aerugin.
Cefuroxime
5
>32
1.0
Resolution
Eradication
1.0
Resolution
Eradication
0.25
Failure
Eradication
Resolution
Eradication
0.25
Resolution
Eradication
2.0
Resolution
Eradication
0.5
Improvement
Eradication
1.0
Improvement
Persistence
Failure
Eradication
7
50
F
Gram
8
52
F
Gram
9
34
M
10
70
F
11
38
F
Gram
+ cocci
12
40
F
Gram
+
13
38
M
Gram - rods
14
39
M
Gram
cocci
S. aureus
Cefuroxime
4
8
15
23
F
Gram
cocci
S. aureus
Gentamicin
5
>32
cocci
S. aureus
Ampicillin
7
>32
0.25
cocci
Streptococ.
Cefuroxime
5
16
0.12
+ + + +
cocci
Streptococ.
Gentamicin
6
8
cocci
S. aureus
Miocamicin
6
cocci
Streptococ.
Cefuroxime
5
4
16
22
F
17°
39
F
+ + Gram + Gram +
18
23
F
Gram
19
29
F
Gram
20
74
F
Gram
cocci
S. aureus
Amoxicillin
6
16
Gram - rods
E. coli
Cefuroxime
6
8
0.25
+ cocci + cocci Gram + cocci
21
43
F
Gram
22
36
M
cocci
23
18
F
Gram
S. aureus
Lincomycin
5
16
0.25
Resolution
Eradication
24
29
M
Gram
S. aureus
Miocamicin
6
8
0.25
Improvement
Eradication
25
45
M
Streptococ.
Amoxicillin
7
16
0.25
Resolution
Eradication
a;
tis.
before treatment;
b;
Cultureb Results
MIC b (llg/ml) Ciprofloxacin
P. aerugin
0.5
K. pneumoniae
0.5
S. aureus
2
S. aureus
0.5
24 hours after the interruption of the therapy and 14 days later (follow up); 0; patient not evaluable because of interruption of treatment after three days due to onset of glossi-
101
ORAL CIPROFLOXACIN FOR TREATMENT OF ACUTE BACTERIAL PHARYNGOTONSILUTIS
RESULTS
One patient out of 25 was not evaluable for the therapeutic efficacy of the treatment as he had to interrupt the therapy as reported below, therefore only 24 patients were evaluated in the present study. All data concerning the demographic, clinical and microbiological characteristics of the patients are reported in Table 3.
Bacterial etiology Twenty-seven bacteria were isolated from bacterial cultures and considered responsible pathogens of the pharyngotonsillitis under examination. Gram-positive cocci (13 S. au reus and 6 Streptococcus spp) were more frequently isolated than gram-negative bacilli (5 Pseudomonas aeruginosa, 1 Serratia marcescens, 1 Proteus vulgaris, 1 Escherichia coli). Both gram-positive and gramnegative bacteria were sensitive in vitro to ciprofloxacin (Table 4).
Clinical and bacteriological results Clinical cure was observed in 15 patients (63%), improvement in 7 patients (29%) and failure in 2 patients (8%). Failures occurred in patients affected by pharyngotonsillitis due to
S. aureus. No patient showed relapse two weeks after the end of the therapy (follow-up). Bacteriological eradication occurred in 20 patients (84%), persistence in 2 patients (8%) and superinfection in 1 patient (4%). The last was caused by a Klebsiella pneumoniae strain. Both the patients with bacteriological persistence of the responsible bacteria (S. aureus and P. aeruginosa) had a significant clinical improvement. The duration of therapy ranged from 5 to 10 days (average 6.7 days).
Side-effects No side-effect was recorded during the present clinical study, but one glossitis occurring two days after the beginning of the therapy and strongly disturbing the patient, who decided consequently to interrupt the treatment_ The glossitis quickly improved after the interruption of the treatment and completely disappeared after three days. This patient was of course not evaluable for the clinical and bacteriological response. No statistically significant change was observed in the hematological and biochemical analysis or urinalysis performed before and after treatments.
DISCUSSION
4 - In vitro sensitivity of causative organism to ciprofloxacin. TABLE
Organism *
No.
P. aeruginosa S. marcescens P. vulgaris E. coli S. aureus Streptococcus **
MIC range (!lgfml)
5 1 1 1 13 6
::5
0.125-1 0.5 0.5 0.5 0.25-2 0.003-1
* Mixed cultures in two patients: S. aureus + S marcescens and S. aureus + P. aeruginosa. ** viridans (4), pneumoniae (2).
TABLE
No. (%) patients 15 (63) 7 (29) 2 (8)
5 - Clinical and bacteriological response. Clinical response Cure Improvement Failure
No. (%) patients 20 (84) 3 (12) 1 (4)
Bacteriological response Eradication Persistence Superinfect.
Bacterial pharyngotonsillitis is usually caused by group A j3-haemolyticus streptococci that are highly sensitive to j3-lactams, macroc lides, lincomycin and other antibiotics which represent the first choice therapy for infections at this site. Most of the patients affected by acute pharyngotonsillitis suspected bacterial etiology usually undergo, in our regions, empirical antibiotic with therapies without performing bacterial examination and these therapies are almost always successful 8. Consequently very few patients after antibiotic therapy continue to suffer from acute pharyngotonsillitis, especially if the infections are caused by j3-haemolyticus streptococci, which are particularly sensitive to the antibiotics usually utilized in clinical practice. On the other hand, the emergence of multiresistant S. aureus and the possible role of path-
112
ogens of some different bacteria such as Pseudomonas sp., even in the pharynx and tonsils, or the low penetration of some antibiotic compounds at that site, could be responsible for the failure of these therapies. The distinction among acute viral and bacterial pharyngotonsillitis still remains uncertain even for otorhinolaryngologists when bacterial cultures are performed, because it is always difficult to state which bacteria are responsible at this site. Nevertheless, the contemporary clinical resolution or improvement and the eradication of bacteria considered as those responsible following the antibiotic therapies, could strongly support and confirm the etiological role of bacteria isolated in the course of acute pharyngotonsillitis in the present study. The favorable clinical results observed in the present study c0nfirm the promises that the excellent microbiological and pharmacokinetic characteristics of ciprofloxacin have suggested. The high tissue penetration of ciprofloxacin after oral administration which determines high drug concentrations in the tonsillar tissue, and the wide antibacterial spectrum which also includes Pseudomonas sp, were certainly very good warranties. In fact, ciprofloxacin at the dosage of 250 mg twice a day cured within a few days a very high percentage of patients affected by acute pharyngotonsillitis, even when caused by such a difficult to eradicate bacteria as P. aeruginosa. Other data available at the present time in the literature which evaluate the therapeutic efficacy of ciprofloxacin at low dosages in the treatment of bacterial pharyngotonsillitis are studies from]apan (200 mg two or three times a day given orally), which confirm our successful results 4,9. Mori and Saito, in fact, in two different
S. ESPOSITO - G. n'ERRICO - C. MONTANARO
studies, obtained an 86% efficacy rate in 24 and 30 patients respectively affected by acute tonsillitis or chronic tonsillitis in acute stage and treated with 100-200 mg of ciprofloxacin given orally 2-3 times a day. Ciprofloxacin is not prescribable to children because of its possible side effects on cartilage growth, and is not a first choice antibiotic in the treatment of pharyngotonsillitis, but the present results suggest that it can be usefully employed when infections are not caused, as is often the case, by ~-haemolyticus streptococcus, and especially if failures of conventional empirical therapies have occurred. ACKNOWLEDGEMENTS: We wish to thank Mr. Giacomo Buonocore for his technical assistance.
REFERENCES 1 Brien JH. Streptococcal pharyngitis optimal site for throat culture. J Ped 1985; 106: 781-782. 2 Brook I, Yokum P. Bacteriology of chronic tonsillitis in young adults. Arch Otolaryngol 1984; 110: 803-807. 3 Esposito S, Galante D, Barba D, D'Errico G, Mazzone A, Montanaro C. Ciprofloxacin concentrations in human fluids and tissue following a single oral dose. Int J Clin Pharm Res 1987; VII, (3): 181-187. 4 Mori Y, Baba S, Kinoshita H, Suzuki K, Shimada J. Laboratory and clinical study of ciprofloxacin (Bay 0 9867) in the otorhinolaryngological field. Chemotherapy, 1985; 33, suppl. 7: 978-985. , Falser N, Dalhoff A, Weuta H. Ciprofloxacin concen· trations in tonsils following a single intravenous infusion. Infection 1985; 12: 355-357. • King A, Shannon K, Phillips I. The «in vitro» activity of enoxacin and ofloxacin compared with that of ciprofloxacin. J Antimicrob Chemother 1985; 15: 551-558. 7 Wise R, Andrews JM, Edwards LJ. «In vitro» activity of Bay 0 9867, a new quinoline derivative, compared with those of other antimicrobial agents. Antimicrob Agents Chemother 1983; 23, 4: 559-564. • Thompkins RK. Managing pharyngitis without throat culture. J Fam Pract 1979; 8: 629-632.
ISSN: 1120-009X (Print) 1973-9478 (Online) Journal homepage: http://www.tandfonline.com/loi/yjoc20
Oral Ciprofloxacin for Treatment of Acute Bacterial Pharyngotonsillitis S. Esposito, G. D’Errico & C. Montanaro To cite this article: S. Esposito, G. D’Errico & C. Montanaro (1990) Oral Ciprofloxacin for Treatment of Acute Bacterial Pharyngotonsillitis, Journal of Chemotherapy, 2:2, 108-112, DOI: 10.1080/1120009X.1990.11738992 To link to this article: http://dx.doi.org/10.1080/1120009X.1990.11738992
Published online: 14 Jul 2016.
Submit your article to this journal
View related articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=yjoc20 Download by: [Monash University Library]
Date: 17 November 2016, At: 22:44
Journal of Chemotherapy
Oral Ciprofloxacin for Treatment of Acute Bacterial Pharyngotonsillitis S. ESPOSITO - G. D'ERRICO * C. MONTANARO *
Summary -------------------------------The clinical efficacy and tolerability of ciprofloxacin orally administered at the dosage of 250 mg twice a day was evaluated in 25 patients affected by acute bacterial pharyngotonsillitis_ All patients were non-responders to previous conventional antibiotic therapies due to in vitro resistance of the responsible bacteria, or possibly the low antibiotic concentration at the infection site. None of the patients had infections caused by group A ~-haemolyticus streptococcus_ Treatment with ciprof10xacin lasted for 5 -1 0 days (mean 6 _7). A favorable clinical response was observed in 92% of patients (15 resolutions and 7 improvements) at the end of the therapy and two weeks later (follow-up). One patient was not evaluable because of the unfortunate onset of glossitis that caused the interruption of the treatment. No other side-effects were recorded in the other 24 patients. The bacteriological response was excellent: 83% bacteriological eradication, 13% persistence and superinfection in only one patient (4%). Ciprofloxacin administered orally at low dosages is highly effective in the treatment of bacterial pharyngotonsillitis and is also well tolerated. Key words: ciprofloxacin, pharyngotonsillitis, quinolones, tonsillitis.
Clinic of Infectious Diseases, First Medical School, University of Naples, Italy. * Clinic of Otorhinolaryngology, First Medical School, University of Naples, Italy. Address: Dr. Silvano Esposito, Clinica Malattie Infettive, (Ospedale Gesu e Maria), Via D. Cotugno 1 - 80135 Naples, Italy. © Edizioni Riviste Scientifiche - Firenze
Vol. 2 - n. 2 (108-112) - 1990
INTRODUCTION
Acute bacterial pharyngotonsillitis usually has a viral etiology. Nevertheless, bacterial pharyngotonsillitis is not infrequently observed in both pediatric and adult patients 1,2. B-haemolyticus group A streptococcus is certainly the most important and frequent patho-' gen responsible for these infections, especially in childhood, but also other microorganisms which are usually present at the pharyngotonsillar site, such as Staphylococcus aureus, Streptococcus viridans, Streptococcus pneumoniae, Haemophilus, Neiserria, Pseudomonas and Enterobacteria, are occasionally considered as responsible pathogens even in non-immuncompromised hosts. It is still not easy to differentiate between bacterial and viral pharyngotonsillitis, both by clinical and bacteriological examination. Cipro£1oxacin is a new £1uoroquinolone which possesses very high in vitro activity against most of the above mentioned pathogens and penetrates the tonsillar tissue well. Mori et al found a concentration of 1.24 Jlg/g in the tonsillar tissue one hour after the administration of a single 200 mg oral dose. We determined in another study that two hours after the administration of a single oral 250 mg dose, the concentration of cipro£1oxacin in the tonsillar tissue was 2.4 Jlg/mg 3-5. These concentrations are equal to or higher than the serum concentrations and greatly exceed the minimal inhibitory concentrations of cipro£1ocacin against the above mentioned pathogens 6,7 In spite of the good pharmacokinetic data concerning the penetration of cipro£1oxacin into ISSN 1120-009X
ORAL CIPROFLOXACIN FOR TREATMENT OF ACUTE BACTERIAL PHARYNGOTONSll..UTIS
the tonsils, few data are available so far concerning the treatment of bacterial pharyngotonsillitis with low dosages of ciprofloxacin so its efficacy at this dosage has not yet been well determined. The aim of the present study was to evaluate the clinical efficacy and tolerability of a low dose regimen of ciprofloxacin given orally in the treatment of acute bacterial pharyngotonsillitis.
MATERIAL AND METHODS
Twenty-five adult patients (14 males and 11 females) aged between 22 and 70 years (average 40 years) with acute pharyngotonsillitis were admitted to a non-comparative, prospective clillical study (see Table 1). TABLE
1 - Characteristics of the patients No. patients
14*
Males Females Age (mean) 40 years
11
* One patient not evaluable
The clinical diagnosis was done according to the following clinical signs and symptoms: mucositis (100%), tonsillar exudate (100%), fever (32%), dysphagia (60%), and satellite adenopathy (48%). All patients had been taking other conventional antimicrobial drugs in the previous week for at ~east four days at standard dose regimens without significant improvement in the subjective symptoms (Table 2).
TABLE
2 - Previous antibiotic treatments No. pts
Ampicillin Amoxicillin Cefuroxime Lincomycin Miocamicin Gentamicin
4 5 5 4 2
5
Dosages
1g 1g 1g
X X X
2 p.o. 2 p.o. 2 Lm.
600 mg X 2 Lm. 150 mg X 2 p.o. 80 mg X 2 Lm.
109
The reason for the failures of the previous therapies was probably the resistance that we detected in vitro in some responsible bacteria to the antibiotics utilized during prior treatment; or possibly the low concentrations of the drug at the site of infection. Pregnancy, age under 18 years and history of hypersensitivity or allergy to quinolone derivatives, and impaired renal function were criteria for exclusion of the patients from the study. All patients gave their informed consent after the nature of the procedures had been fully explained. No patient was affected by diabetes and/or other underlying diseases. Ciprofloxacin was given orally at a dosage of 250 mg twice a day for 5-10 days (average 6.7 days). Ciprofloxacin was kindly provided by Bayer Italia Spa, Milan, Italy. The clinical responses were stated according to the improvement or disappearance of the above mentioned signs; the bacteriological responses according to the eradication or persistence, at the end of therapy, of bacteria considered responsible. The bacteriological culture of tonsillar exudate, frequently obtained by tonsillar squeezing, was performed before each therapy and, if exudate was still present, during and after the end of treatment. All the responsible bacteria were investigated for their susceptibility to ciprofloxacin and other conventional antibiotics by determining the minimal inhibitory concentrations (MIC) by a microdilution broth method. The breakpoint for ciprofloxacin susceptibility was considered 2
Jlg/rn1. The clinical signs of the infection were examined and noted every 2-3 days during the treatment. Clinical and microbiological followup of the patients cured at the end of the therapy was done two weeks later. Possible adverse reactions and side-effects were carefully researched by inquiry. Clinical examination was carried out two weeks after the end of the therapy (follow-up). The main blood biochemical tests (urea, glucose, creatinine, SGOT, SGPT, Alp, bilirubin, ESR, RBC, WBC, hemoglobin, platelets, total proteins and urinalysis) were performed before the beginning and after the end of each therapy. These data were successively evaluated and compared by Student's «t» test.
TABLE
No.
Age (years)
Sex
Gram Staina
1
46
F
Gram - rods
2
67
F
Gram
3
34
M
Gram
4
28
M
5
48
M
6
20
M
+
cocci
+ rods Gram + cocci Gram + cocci Gram + cocci + +
3 - Clinical, microbiological and demographic data of the patients. MIca (llg/mI)
Response
Culturea Results
Prior Therapy
P. aerugin
Ampicillin
5
8
0.25
Improvement
Persistence
S. aureus + S. marcesc
Amoxicillin
5
4 1
1.0 0.5
Resolution
Eradication
P. vulgaris
Amoxicillin
6
32
0.5
Resolution
Superinfection
S. aureus
Ampicillin
6
16
0.25
Resolution
Eradication
Streptococ.
Gentamicin
7
8
0.003
Resolution
Eradication
S. aureus + P. aerugin
Lincomycin
4
4
2.0 1.0
Improvement
Eradication
>32
Duration (days)
Prior drug
Ciprofloxacin
Clinical
Bacteriological
cocci
S. aureus
Miocamicin
7
16
0.5
Improvement
Persistence
cocci
S. aureus
Gentamicin
5
8
1.0
Resolution
Eradication
Gram - rods
P. aerugin
Gentamicin
7
8
0.015
Improvement
Eradication
Gram - rods
P. aerugin.
Amoxicillin
6
>32
0.5
Resolution
Eradication
S. aureus
Ampicillin
5
>32
0.5
Resolution
Eradication
Streptococ.
Miocamicin
4
2
1.0
Resolution
Eradication
P. aerugin.
Cefuroxime
5
>32
1.0
Resolution
Eradication
1.0
Resolution
Eradication
0.25
Failure
Eradication
Resolution
Eradication
0.25
Resolution
Eradication
2.0
Resolution
Eradication
0.5
Improvement
Eradication
1.0
Improvement
Persistence
Failure
Eradication
7
50
F
Gram
8
52
F
Gram
9
34
M
10
70
F
11
38
F
Gram
+ cocci
12
40
F
Gram
+
13
38
M
Gram - rods
14
39
M
Gram
cocci
S. aureus
Cefuroxime
4
8
15
23
F
Gram
cocci
S. aureus
Gentamicin
5
>32
cocci
S. aureus
Ampicillin
7
>32
0.25
cocci
Streptococ.
Cefuroxime
5
16
0.12
+ + + +
cocci
Streptococ.
Gentamicin
6
8
cocci
S. aureus
Miocamicin
6
cocci
Streptococ.
Cefuroxime
5
4
16
22
F
17°
39
F
+ + Gram + Gram +
18
23
F
Gram
19
29
F
Gram
20
74
F
Gram
cocci
S. aureus
Amoxicillin
6
16
Gram - rods
E. coli
Cefuroxime
6
8
0.25
+ cocci + cocci Gram + cocci
21
43
F
Gram
22
36
M
cocci
23
18
F
Gram
S. aureus
Lincomycin
5
16
0.25
Resolution
Eradication
24
29
M
Gram
S. aureus
Miocamicin
6
8
0.25
Improvement
Eradication
25
45
M
Streptococ.
Amoxicillin
7
16
0.25
Resolution
Eradication
a;
tis.
before treatment;
b;
Cultureb Results
MIC b (llg/ml) Ciprofloxacin
P. aerugin
0.5
K. pneumoniae
0.5
S. aureus
2
S. aureus
0.5
24 hours after the interruption of the therapy and 14 days later (follow up); 0; patient not evaluable because of interruption of treatment after three days due to onset of glossi-
101
ORAL CIPROFLOXACIN FOR TREATMENT OF ACUTE BACTERIAL PHARYNGOTONSILUTIS
RESULTS
One patient out of 25 was not evaluable for the therapeutic efficacy of the treatment as he had to interrupt the therapy as reported below, therefore only 24 patients were evaluated in the present study. All data concerning the demographic, clinical and microbiological characteristics of the patients are reported in Table 3.
Bacterial etiology Twenty-seven bacteria were isolated from bacterial cultures and considered responsible pathogens of the pharyngotonsillitis under examination. Gram-positive cocci (13 S. au reus and 6 Streptococcus spp) were more frequently isolated than gram-negative bacilli (5 Pseudomonas aeruginosa, 1 Serratia marcescens, 1 Proteus vulgaris, 1 Escherichia coli). Both gram-positive and gramnegative bacteria were sensitive in vitro to ciprofloxacin (Table 4).
Clinical and bacteriological results Clinical cure was observed in 15 patients (63%), improvement in 7 patients (29%) and failure in 2 patients (8%). Failures occurred in patients affected by pharyngotonsillitis due to
S. aureus. No patient showed relapse two weeks after the end of the therapy (follow-up). Bacteriological eradication occurred in 20 patients (84%), persistence in 2 patients (8%) and superinfection in 1 patient (4%). The last was caused by a Klebsiella pneumoniae strain. Both the patients with bacteriological persistence of the responsible bacteria (S. aureus and P. aeruginosa) had a significant clinical improvement. The duration of therapy ranged from 5 to 10 days (average 6.7 days).
Side-effects No side-effect was recorded during the present clinical study, but one glossitis occurring two days after the beginning of the therapy and strongly disturbing the patient, who decided consequently to interrupt the treatment_ The glossitis quickly improved after the interruption of the treatment and completely disappeared after three days. This patient was of course not evaluable for the clinical and bacteriological response. No statistically significant change was observed in the hematological and biochemical analysis or urinalysis performed before and after treatments.
DISCUSSION
4 - In vitro sensitivity of causative organism to ciprofloxacin. TABLE
Organism *
No.
P. aeruginosa S. marcescens P. vulgaris E. coli S. aureus Streptococcus **
MIC range (!lgfml)
5 1 1 1 13 6
::5
0.125-1 0.5 0.5 0.5 0.25-2 0.003-1
* Mixed cultures in two patients: S. aureus + S marcescens and S. aureus + P. aeruginosa. ** viridans (4), pneumoniae (2).
TABLE
No. (%) patients 15 (63) 7 (29) 2 (8)
5 - Clinical and bacteriological response. Clinical response Cure Improvement Failure
No. (%) patients 20 (84) 3 (12) 1 (4)
Bacteriological response Eradication Persistence Superinfect.
Bacterial pharyngotonsillitis is usually caused by group A j3-haemolyticus streptococci that are highly sensitive to j3-lactams, macroc lides, lincomycin and other antibiotics which represent the first choice therapy for infections at this site. Most of the patients affected by acute pharyngotonsillitis suspected bacterial etiology usually undergo, in our regions, empirical antibiotic with therapies without performing bacterial examination and these therapies are almost always successful 8. Consequently very few patients after antibiotic therapy continue to suffer from acute pharyngotonsillitis, especially if the infections are caused by j3-haemolyticus streptococci, which are particularly sensitive to the antibiotics usually utilized in clinical practice. On the other hand, the emergence of multiresistant S. aureus and the possible role of path-
112
ogens of some different bacteria such as Pseudomonas sp., even in the pharynx and tonsils, or the low penetration of some antibiotic compounds at that site, could be responsible for the failure of these therapies. The distinction among acute viral and bacterial pharyngotonsillitis still remains uncertain even for otorhinolaryngologists when bacterial cultures are performed, because it is always difficult to state which bacteria are responsible at this site. Nevertheless, the contemporary clinical resolution or improvement and the eradication of bacteria considered as those responsible following the antibiotic therapies, could strongly support and confirm the etiological role of bacteria isolated in the course of acute pharyngotonsillitis in the present study. The favorable clinical results observed in the present study c0nfirm the promises that the excellent microbiological and pharmacokinetic characteristics of ciprofloxacin have suggested. The high tissue penetration of ciprofloxacin after oral administration which determines high drug concentrations in the tonsillar tissue, and the wide antibacterial spectrum which also includes Pseudomonas sp, were certainly very good warranties. In fact, ciprofloxacin at the dosage of 250 mg twice a day cured within a few days a very high percentage of patients affected by acute pharyngotonsillitis, even when caused by such a difficult to eradicate bacteria as P. aeruginosa. Other data available at the present time in the literature which evaluate the therapeutic efficacy of ciprofloxacin at low dosages in the treatment of bacterial pharyngotonsillitis are studies from]apan (200 mg two or three times a day given orally), which confirm our successful results 4,9. Mori and Saito, in fact, in two different
S. ESPOSITO - G. n'ERRICO - C. MONTANARO
studies, obtained an 86% efficacy rate in 24 and 30 patients respectively affected by acute tonsillitis or chronic tonsillitis in acute stage and treated with 100-200 mg of ciprofloxacin given orally 2-3 times a day. Ciprofloxacin is not prescribable to children because of its possible side effects on cartilage growth, and is not a first choice antibiotic in the treatment of pharyngotonsillitis, but the present results suggest that it can be usefully employed when infections are not caused, as is often the case, by ~-haemolyticus streptococcus, and especially if failures of conventional empirical therapies have occurred. ACKNOWLEDGEMENTS: We wish to thank Mr. Giacomo Buonocore for his technical assistance.
REFERENCES 1 Brien JH. Streptococcal pharyngitis optimal site for throat culture. J Ped 1985; 106: 781-782. 2 Brook I, Yokum P. Bacteriology of chronic tonsillitis in young adults. Arch Otolaryngol 1984; 110: 803-807. 3 Esposito S, Galante D, Barba D, D'Errico G, Mazzone A, Montanaro C. Ciprofloxacin concentrations in human fluids and tissue following a single oral dose. Int J Clin Pharm Res 1987; VII, (3): 181-187. 4 Mori Y, Baba S, Kinoshita H, Suzuki K, Shimada J. Laboratory and clinical study of ciprofloxacin (Bay 0 9867) in the otorhinolaryngological field. Chemotherapy, 1985; 33, suppl. 7: 978-985. , Falser N, Dalhoff A, Weuta H. Ciprofloxacin concen· trations in tonsils following a single intravenous infusion. Infection 1985; 12: 355-357. • King A, Shannon K, Phillips I. The «in vitro» activity of enoxacin and ofloxacin compared with that of ciprofloxacin. J Antimicrob Chemother 1985; 15: 551-558. 7 Wise R, Andrews JM, Edwards LJ. «In vitro» activity of Bay 0 9867, a new quinoline derivative, compared with those of other antimicrobial agents. Antimicrob Agents Chemother 1983; 23, 4: 559-564. • Thompkins RK. Managing pharyngitis without throat culture. J Fam Pract 1979; 8: 629-632.
