ani^ and George Taibot^. 'Department of ... Dr. Frederic Barnett, University of Pennsylvania,. School of .... again after 4 weeks and the fistula was still present.
Case report
Ciprofloxacin treatment of periapical Pseudomonas aeruginosa infection Barnett F, Axelrod P, Tronstad L, Slots J, Graziani A, Talbot G. Ciprofloxacin treatment of periapical Pseudomonas aeruginosa infection. Endod Dent Traumatol 1988; 4: 132-137. Abstract - Survival of bacteria in periapical tissues may be the reason for endodontic failures. This case report describes the treatment of a patient with periapical lesions refractory to endodontic treatment. Microbiological sampling from fistulae associated with the lesions revealed the presence of Pseudomonas aeruginosa. Phenoxymethyl penicillin, metronidazole and carbenicillin were ineffective in eliminating the periapical infection. However, an investigational antibiotic, ciprofloxacin, which was administered orally twice daily for 15 weeks, proved to be an effective, safe and convenient medicament in the treatment of periapical Pseudomonas aeruginosa infection. The fistulae closed in less than 2 weeks and a radiograph taken during the fourteenth week of therapy showed healing of the apical periodontitis with osseous regeneration. It is suggested that ciprofloxacin is a valuable agent in the treatment of apical periodontitis, and probably other odontogenic infections caused by susceptible aerobic gram-negative bacilli.
Frederic Barnett\ Peter Axeirod^ Leif Tronstad', Jorgen Siots', Amy Graziani^ and George Taibot^ 'Department of Endodontics, School of Dental Medicine, 'Section of Infectious Diseases, Scfiool of Medicine, 'Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
Key words: ciprofloxacin, apical periodontitis, Pseudomonas aeruginosa infection. Dr. Frederic Barnett, University of Pennsylvania, School of Dental Medicine, Department of Endodontics, 4001 Spruce St., Philadelphia, PA 19104 USA. Accepted for publication 4 January 1988.
It has been demonstrated that micro-organisms may any past history of rheumatic fever, congenital heart survive and maintain an infectious disease process disease, valvular disease, or hypertension. in periapical tissues, inaccessible to conventional The dental history revealed that 7 years ago the endodontic treatment (1-4). Survival of bacteria patient had suffered an injury with coronal fracture outside the root canal, threfore, may be the reason of the maxillary incisors. Following the injury, the for endodontic failures. This case report describes maxillary incisors had been endodontically treated the treatment of a patient with periapical lesions and restored with crowns. The clinical examination infected with Pseudomonas aeruginosa which were re- revealed acrylic and gold crowns on the maxillary fractory to endodontic treatment but which were incisors which were functionally and esthetically accured by systemic use of ciprofloxacin. ceptable. The gingiva and alveolar mucosa were of normal color, consistency and contour as there was no gingivitis, recession, swelling or fistulae. Probing Case report periodontal pocket depths were within normal limits Examination, diagnosis and treatment pian and there was no bleeding upon probing. The A 45-year-old female was referred for examination maxiflary right central and lateral incisors were of the maxillary right lateral and central incisor slightly sensitive to percussion. teeth. Her chief complaint was that of occasional The radiographic examination revealed root fifldiscomfort to mastication associated with these ings, posts and crowns associated with the maxillary teeth. incisors. The root filling material appeared to be The medical history revealed a heart murmur of gutta-percha. In the maxillary right central and unknown origin, and the patient's physician reclateral incisors the root fillings terminated about ommended the use of antibiotic prophylaxis in con^ 1 mm short of the radiographic apices (Fig. 1). junction with dental treatment. The patient denied No voids were discernible between the root fillings 132
Periapicai Pseudomonas aoruginosa infection
and the root canal walls, but a space existed between the gutta-percha and the metallic posts. Radiolucencies with a diameter of about 4 mm were evident at the apices of these teeth (Fig. 1). The clinical diagnosis was Asymptomatic apical periodontitis of the maxillary right central and lateral incisor teeth. The treatment plan comprised surgical-endodontic treatment of the 2 teeth with apicoectomies and retrograde root fillings. Surgical-endodontic treatment
The patient was given 2 g of phenoxymethyl penicillin 1 h prior to the surgical operation. Xylocaine with 1:100,000 epinephrine was used to establish anesthesia. A sulcular full thickness flap was elevated from the distal aspect of the right maxillary canine to the distal aspect of the left central incisor. Two defects in the labial cortical bone corresponding to the apices of the right central and lateral incisors then became evident. Granulation tissue
Fig. 1. Preoperative radiograph of root filled maxillary right incisors. Periapical radiolucencies, 4 mm in diameter, are observed at the apices of the teeth.
which was present in the defects was curetted out, revealing the apices of the teeth. Labial cortical bone was then removed using a high-speed handpiece and a no. 8 round bur under irrigation with sterile saline to adequately expose the root ends. Approximately 4 mm of the roots were removed, using the high-speed handpiece and a cross-cut fissure bur under saline irrigation. Retrograde cavities encompassing the root canals were made using a micro contra-angle handpiece and a micro invertedcone bur no. 32. Copahte cavity varnish was then applied to the cavities using sterile paper points, and a copper-containing spherical amalgam was used for the retrograde fillings (5) (Fig. 2). The flap was repositioned and secured with interrupted 4—0 silk sutures, and the patient was given 1 g penicillinVK to take 6 h after the first dose. Acetaminophen with 30 mg codeine was prescribed as needed for pain and postoperative instructions were given. The patient returned after 7 days for suture removal. She was without symptoms and the soft tissue healing was without complications.
Fig. 2. Postsurgical radiograph of maxillary right incisors. Retrograde amalgam fillings are observed.
133
Barnett et al.
Two months after the surgical-endodontic treatment the patient returned with a fistula in the bueco-alveolar mueosa over the right lateral ineisor. A gutta-percha cone size no. 35 was inserted into the fistula and a periapical radiograph was taken. The radiograph revealed that the fistula originated from the periapical area of the lateral ineisor (Fig. 3). Metronidazole (Flagyl, Searle, Chieago, IL, USA) 500 mg to be taken every 6 h was then empirieally preseribed for 10 days. The patient was examined again after 4 weeks and the fistula was still present. Microbiological findings
An attempt was then made to identify the pathogenic organisms and a microbiological sample was taken through the fistulous traet. The buecal mucosa in the right lateral incisor area was isolated from the rest of the oral eavity by sterile gauze and cotton rolls. The mucosa was then washed repeatedly with Betadine followed by 70% alcohol and
stretched with 2 fingers so that the fistulous tract was maximally opened. A sterile paper point was introduced into the fistula and after removal was plaeed into a vial containing 3 ml of Moller's VMGA III transport medium (6). The sample was then proeessed using a continuous anaerobie technique (3). Plating took place onto enriched Brucella blood agar medium. After parallel incubation for 3 days in 10% earbon dioxide and 90% air at 35°C and for 7 days in a Coy anaerobie ehamber (Coy Laboratory Products, Ann Arbor, MI, USA) containing 85% nitrogen, 10% hydrogen and 5% carbon dioxide, at 35°C, the baeterial eolonies were counted and isolates were speeiated using established methods and taxonomieal sehemes. Antibiotic sensitivity testing was also performed according to established methods. The cultural and sensitivity data are shown in Table 1. The micro-organisms reeovered from the fistula were identified as Pseudomonas aeruginosa, Staphylococcus epidermidis and a Streptococcus species.
Pseudomonas aeruginosa was resistant to tetracycline, penieillin G, and erythromyein, and was sensitive to carbenicillin. Accordingly, the patient was given Ceocillin (Roerig, New York, NY, USA), 2 tablets every 6 h for 14 days. Eaeh tablet of Geocillin contains carbenieillin indanyl sodium equivalent to 382 mg of carbenicillin. The patient tolerated the medication well. After 3 weeks the patient was examined again. The fistula from the lateral ineisor was unehanged and, in addition, a second fistula was now present in the buecal mueosa over the right eentral incisor. Both fistulae were patent and could be traeed with gutta-pereha eones to the apiees of the lateral and eentral incisors (Fig. 4). Microbiological sampling from both fistulae was performed as deseribed above, and the cultural and sensitivity data are shown in Table 2. The Staphylococcus and Streptococcus species were not recovered at this time. Pseudomonas aeruginosa was identified in the samples from both fistulae, and Propionibacterium acnes was reeovered from both fistulae as well. Pseudomonas aeruginosa again tested sensitive to carbenieillin, which clinically had proven to be ineffective. At this time, the patient was enrolled in an open study on the efficacy
Table 1. Identity and antibiotic sensitivity of bacteria isolated from fistula associated with maxillary right lateral incisor.
134
9.0 X 10^ 2.8x102 9.0x10'
Antibiotic sensitivity E C T P
1 -1- +
Fig. 3. Radiograph of maxillary right incisor area 2 months following endodontic surgery. A buccal fistula originating from the lateral incisor is traced with gutta-percha cone.
Pseudomonas aeruginosa Staphylococcus epidermidis Streptococcus sp.
No. of colony forming units
-1- -1- 1
Bacteria
-1-1-
-1-
T = tetracycline HCI; P = penicillin G; E = erythromyein; C = carbenicillin.
Periapical Pseadomonas aeruginosa infection age, trismus, dysphagia, or diplopia. The temperature was 36.9°C. There were 2 whitish nodules, 2 mm in diameter, in the buccal mucosa, 1 above the maxillary right lateral and 1 above the maxillary right central incisor. A pinpoint sinus opening was present in each nodule, and a small amount of purulent material was expressed from both openings. Each nodule was surrounded by approximately 5 mm of erythema. There was otherwise no tenderness, swelling, or fluctuation in the periapical areas or nasal sinuses. The examination ofthe eyes, ears, nose, and neurological system and the general examination were normal. The white blood cell count was 6300/mm3 (65 nentrophils, 26 lymphocytes, 6 monocytes, 2 eosinophils, 1 basophil), hemoglobin 13.9 g/dl, hemocrit 40.9o/o, erythrocyte sedimentation rate (Westergren) 31 mm/h, alkaline phosphatase 76 U/1, LDH 174 U/1, calcium 9.5 mg/ dl, and phosphorus 3.4 mg/dl. The remainder ofthe routine screening blood chemistries and urinalysis were also within normal limits. A computerized tomographic scan of the maxilla, mandible, nasal sinuses, and the brain showed a retention cyst in the right maxillary sinus and minimal mucosal thickening in the left maxillary sinus. An otorhinolaryngological consultant found no abnormalities other than the fistulous tracts in the maxillary mucosa. It was felt that the maxillary sinus cyst bore no relation to the patient's apical periodontitis.
Fig. 4. Radiograph of maxillary right incisor area 4 months following endodontic surgery. Buccal fistulae originating from the lateral and eentral incisors are traeed with gutta-percha cones.
of an experimental drug, ciprofioxacin (Miles Pharmaceuticals, West Haven, CT, USA), in the treatment of Pseudomonas aeruginosa infections.
Physical examination Prior to the onset of ciprofioxacin treatment, the patient underwent a physical examination. At this time she had no pain in the oral cavity or nasal sinuses, and no headache, fever, malodorous drainTable 2. Identity and antibiotic sensitivity of bacteria isolated from fistulae associated with maxillary right lateral and central incisors. Bacteria Pseudomonas aeruginosa Proplontbacterium acnes
No. of colony forming units 1.0 x 10' 1.0 x 10'
Antibiotic sensitivity T P E C +
+
-I-
+ +
T=tetracycline HCl; P = penicillin G; E = erythromycin; C = carbenicillin.
Ciprofioxacin treatment Ciprofioxacin treatment was then inititated. A 750 mg dose was administered twice daily. Blood counts, blood chemistries, and urinalyses were obtained approximately every 2 weeks while the patient re- • ceived therapy. On ciprofioxacin, drainage from the fistulae resolved in less than 2 weeks, and the erythema resolved in 3 weeks. After 6 weeks, the nodule over the central incisor involuted and the nodule over the lateral incisor became less pale in color, smaller (1 mm) and remained stable in size and shape. A periapical radiograph taken during the fourteenth week of therapy showed heafing of the apical periodontitis with osseous regeneration (Fig. 5). Ciprofioxacin was administered for a total of 15 weeks. The only adverse experience was an episode of yeast vaginitis during the third week of therapy. The patient continued to do well without relapse of symptoms or signs of infection during 8 months of post-therapy observation. Discussion There are few reports on the isolation o{ Pseudomonas aeruginosa from oral infections. The organism has been reeovered from periapical lesions refractory to 135
Barnett et al.
line used for irrigation during the surgical operation (3). At any rate, from a clinical point of view the important fact is that the Pseudomonas infection persisted in spite of the optimal treatment rendered. Gram-negative bacilli are an unusual cause of endodontic infection and this case demonstrated the importance and usefulness of careful bacteriological culturing in the treatment of refractory periapical lesions. Carbenicillin possessed good in vitro activity against Pseudomonas aeruginosa, but was ineffective clinically, conceivably because of insufficient serum concentration obtained by the oral route. Traditional antibiotic treatment oi Pseudomonas infeetion of the oral bones has been a parenteral combination of an antipseudomonal penieillin and an aminoglycoside for at least 3 to 4 weeks after the patient has become asymptomatic (11). Our patient was cured after 15 weeks of twice-daily oral ciprofloxacin. Ciprofloxacin is a 6-fluoro-7-piperazine-4-quinolone which is highly active against Pseudomonas aeruginosa, Enterobacteriaceae, Hemophilus influenzae,
Neisser-
ia, and moderately active against aerobic grampositive cocci. It has poor activity against most anaerobic bacteria (15). A number of studies have demonstrated that ciprofloxacin is an effective agent in the treatment oi^ Pseudomonas aeruginosa osteomyel itis (16—19). Clinical cures (resolution of drainage and complete tissue healing) have been achieved in 39-100% of patients, and bacteriological cure rates range from 63-100%. The duration of treatment in successfully treated patients in these trials ranges Fig. 5. Radiograph of maxillary right incisor area at 14th week from 37-191 days (the data concerning therapy of ciprofloxacin therapy. Periapical osseous repair is evident. duration include both patients with Pseudomonas and patients with other gram-negative bacillary osteomyelitis). The emergence of ciprofloxacin-resistant Pseudomonas during therapy is a known eomplication endodontic treatment (3) and from periodontal of ciprofloxacin treatment (20), but this occurred pockets of patients with refractory periodontal diseases (7). Also, Pseudomonas aeruginosa is occasionally in only 4 of 54 patients treated in the above-mentioned case series. seen in other odontogenic orofacial infections (8), and in osteomyelitis of dental origin (9, 10). InforCiprofloxacin is a generally well tolerated antimation concerning clinical features and therapy is biotic (21, 22). In the United States, an adverse scanty. event probably or possibly related to therapy has Pseudomonas aeruginosa has been isolated from the been reported in 16% of patients. Eight percent of patients had a complaint referable to the gastroinpharynx in 2% of health adults (11). The recovery testinal tract (usually nausea or diarrhea), and 3% rate increases with acute hospitalization, the bedridhad a sign or symptom referable to the central den state, respiratory disease, and receipt of antinervous system (usually dizziness, headache, tremor, biotics (12, 13). Our patient had no obvious risk facor restlessness). There have been biochemical abtors for the development of oral colonization with normalities in less than 3% of patients, usually elevgram-negative bacilli. Still, it is possible that her inations of alanine aminotransferase and aspartate fection was the result of the prior root canal treataminotransferase or, rarely, blood urea nitrogen and ment, especially since typical contaminants such as creatinine, but these are usually mild and transient. Staphytococcus epidermidis a n d Propionibacterium acnes Side effects of parenteral antibiotics used in the were reeovered from the periapieal areas as well. However, it is known that Pseudomonas aeruginosa may treatment of aerobic gram-negative rod osteomylitis have been substantially more frequent and more survive in water for lengthy periods of time (14), and severe than those associated with the use of ciprothe possibility exists that the organism was introfloxacin (19). duced into the periapical tissues by means of the sa136
Periapical Pseudomonas aoruginosa infection 9. In our patient, ciprofloxacin was an effeetive, safe, convenient, and inexpensive alternative to pro10. longed parenteral antibiotics in the treatment of periapical Pseudomonas aeruginosa infeetion. Cipro- 11. floxacin should, therefore, be considered as a valuable agent in the treatment of apieal periodontitis 12. and probably of other odontogenie infections caused by susceptible aerobic gram-negative bacilli.
SANDERS B. Current eoncepts in the management of osteomyelitis of the mandible. J Oral Med 1978; 33: 40-3. MAINOUS E G . A study of osteomyelitis following tooth extraction. US Navy Med 1973; 61: 32-4. RosENTHAL S, TAGER IB. Prevalence of gram-negative rods in the normal pharyngeal flora. Ann Intern Med 1975; 83: 355-7. VALENTI W M , TRUDELL RG, BENTLEY DW. Faetors predis-
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13. JoHANSON WG, PIERCE A K , SANFORD J P , THOMAS G D . Non-
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Acknowledgement - The ciprofloxaein study was supthe signifteance of colonization of the respiratory tract. Ann ported by a grant from Miles Pharmaceuticals, West Intern Med 1972; 77: 701-6. Haven, CT, USA. 14. NoLTE WA. Oral microbiology. 4th ed. St. Louis: CV Mosby, 1982; 350-2. 15. SANDERS CC, SANDERS WE, GoERtNG RV. Overview of pre-
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