Methenamine

Study objective: IV antibiotic therapy for 2 to 6 weeks followed by 6 to 12 months of oral antibiotic therapy is usually recommended for the treatment of thoracic actinomycosis. The objective of this study was to evaluate the duration of IV and oral antibiotic therapy for thoracic actinomycosis.

Methods: We present a retrospective case series of 28 patients with thoracic actinomycosis as confirmed by histopathology from October 1994 through December 2003.

Results: After diagnosis of actinomycosis, 54% (15 of 28 patients) received antibiotic therapy alone. The duration of IV antibiotic therapy ranged from 0 to 18 days (median, 2 days; interquartile range [IQR], 0 to 3 days), and the duration of oral antibiotic treatment ranged from 76 to 412 days (median, 167 days; IQR, 142 to 214 days) in patients who received antibiotics alone. Combination surgical and antibiotic therapy occurred in 46% (13 of 28 patients). The duration of IV antibiotic therapy ranged from 3 to 17 days (median, 8 days; IQR, 5 to 13 days), and the duration of oral antibiotic therapy ranged from 0 to 534 days (median, 150 days; IQR, 3.5 to 289 days) in these patients. Clinical cures were achieved in 96% (27 of 28 patients). There was no clinical evidence of recurrence during follow-up period at our hospital (median, 23 months; IQR, 9 to 44 months) in 21 patients, excluding 7 patients who were transferred to referring hospitals after completion of antibiotic therapy (n = 6) or during antibiotic therapy (n = 1).

Conclusions: Thoracic actinomycosis is best treated with individualized therapeutic modalities, depending on factors such as the initial burden of disease, the performance of resectional surgery, and the clinical and radiologic responses to therapy. The traditional recommendation of IV antibiotic therapy for 2 to 6 weeks followed by oral antibiotic therapy for 6 to 12 months is not always necessary for all thoracic actinomycosis patients.

Key words: actinomycosis; antibacterial agents; duration; therapy

Abbreviations: IQR = interquartile range; PTCA = percutaneous fine-needle aspiration

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Actinomycosis is an indolent and slowly progressing infection that is caused by anaerobic or microaerophilic bacteria, principally of the Actinomyces genus. Thoracic involvement is seen in approximately 15% of all aetinomycosis eases and results from the aspiration of oropharyngeal or GI secretions into the respiratory tract. (1-3)

With regard to the treatment of actinomycosis, two principles have evolved based on the clinical experience of the last 50 years. It is necessary to treat the disease both with high doses of antimicrobials and for a prolonged period. The necessity for this intensive treatment is presumably due to the avascularity and induration of infected areas, which is commonly observed in these infections. (1-3) As a general rule, IV administration of the maximal antimicrobial dose for 2 to 6 weeks followed by oral therapy for a duration of at least 6 to 12 months is recommended by a great many review articles and textbooks (1-5) on medicine, infectious diseases, and pulmonary diseases.

However, these recommendations evolved during a time when patients who had actinomycosis normally presented late, with large lesions ("bulky disease"), and when modern imaging modalities for the diagnosis of the disease and monitoring of patient response to treatment were not available. (6) This condition now tends to manifest at an earlier stage. These changes in disease presentation may have resulted from recent improvements in oral hygiene, the ready availability of antibiotics, early diagnosis, and early initiation of treatment whenever a pulmonary infection is suspected. (5) Several investigators (7-10) have reported the successful treatment of thoracic actinomycosis with a relatively brief course of therapy. Nevertheless, an initial several weeks (9, to 6 weeks) of IV antibiotic therapy have classically been described and recommended for the treatment of thoracic actinomycosis. (1-5) However, the necessity of several weeks of IV antibiotic therapy, even in patients with milder manifestations of thoracic actinomycosis, remains a matter of some controversy. If the recommended course of IV therapy is shortened and successfully switched to oral antibiotics, the length of hospital stay could be reduced, as could the cost of care.

In Korea, many clinicians have reported clinical eases of thoracic actinomycosis. Current presentations of thoracic actinomycosis tend to be milder than in past reports, as empyema, sinus fistula, and mediastinitis are now quite rare. (11) In addition, we have frequently experienced the successful resolution of thoracic actinomycosis with short-term IV antibiotics, or even with oral antibiotics only, without the need for IV antibiotics. Therefore, we retrospectively reviewed all cases of thoracic actinomycosis diagnosed in the past 10 years in order to evaluate the duration of IV and oral antibiotic therapy.

MATERIALS AND METHODS

All 28 patients who received a diagnosis of thoracic actinomycosis at the Samsung Medical Center (a 1,250-bed referral hospital in Seoul, Korea) from October 1994 through December 2003 were included in the present study. Confirmatory diagnoses were based on the histopathologic findings of sulfur granules, or Gomori methenamine silver stain-positive branching filamentous organisms. Tissue specimens were obtained from purulent discharge, surgical biopsy, bronchoscopic biopsy, or percutaneous fine-needle aspiration (PTCA) or core biopsy.

The medical records were reviewed for clinical data of the patients, including presenting symptoms, comorbidities, diagnostic procedures, whether thoracotomy was performed, and the duration of IV or oral antibiotic treatment. Simple chest radiography and available chest CT images were also reviewed. The disappearance of both clinical symptoms and main lesions on chest radiography constituted our definition of clinical cure.

The majority of clinical data were not normally distributed. Therefore, all values were expressed as medians and interquartile range (IQR [25 to 75th percentiles]). Statistical software (SPSS 11.0; SPSS, Chicago, IL) was used to calculate medians and IQR.

RESULTS

Clinical Features and Diagnoses of Thoracic Actinomycosis

Twenty-two of the patients (79%) were men, and 6 patients (21%) were women. Their ages ranged from 38 to 81 years (median, 54 years; IQR, 46.5 to 61 years). Seventeen patients (61%) were either currently smokers or were ex-smokers. Fifteen patients (54%) exhibited underlying comorbidities, including diabetes mellitus (n = 7), hypertension (n = 5), previous treatment for pulmonary tuberculosis (n = 3), bronchiectasis (n = 3), chronic hepatitis (n = 3), and idiopathic pulmonary fibrosis (n = 1).

The most frequently seen presenting symptoms included productive sputum (n = 24, 86%), cough (n = 24, 86%), and hemoptysis (n = 22, 79%). Other symptoms included weight loss (n = 6, 21%), chest pain (n = 3, 11%), and fever (n = 2, 7%). The duration of symptoms varied from 2 weeks to 16 months (median, 2.5 months; IQR, 1 to 6 months).

Leukocytosis of the peripheral blood was seen in only 11 patients (39%), and the WBC counts were within normal range in 17 patients (61%) [median, 8,330/[micro]L; IQR, 7,275 to 11,820/[micro]L]. In the 11 patients with increased WBC counts, leukocytosis was normalized after 1 to 3 months of antibiotic therapy. Because many patients received a presumptive diagnosis of lung cancer based on initial clinical and radiologic findings, the erythrocyte sedimentation rate and the C-reactive protein were measured in only 19 patients (68%) and 13 patients (46%), respectively. In these patients, 63% presented with increased erythrocyte sedimentation rate (median, 39 mm/h; IQR, 29 to 67 mm/h) and 85% showed increased C-reactive protein (median, 1.4 mg/dL; IQR, 0.34 to 10.35 mg/dL).

Chest radiography and CT were performed on all patients. Radiologic findings were categorized as consolidation (n = 17, 61%), nodular or mass-like lesions (n = 9, 32%), and atelectasis (n = 2, 7%). The most common CT findings included central necrosis (n = 18, 64%), cavities (n = 12, 43%), mediastinal or hilar lymphadenopathy (n = 14, 50%), endobronchial calcified nodules (broncholiths) In = 10, 34%], and pleural effusion (n = 6, 21%). The confirmatory diagnosis of thoracic actinomycosis was decided by surgical lung biopsy (n = 11; six lobectomies, two segmentectomies, and three wedge resections), PTCA or core biopsy (n = 10), bronchoscopic biopsy (n = 6), and transbronchial lung biopsy (n = 1).

Treatment of Thoracic Actinomycosis in 15 Patients Who Received Antibiotics Alone

After the diagnosis of actinomycosis, 54% (15 of 28 patients) received antibiotic therapy alone. The duration of IV antibiotic treatment ranged from 0 to 18 days (median, 2 days; IQR, 0 to 3 days). Seven patients received oral antibiotic therapy without IV antibiotics, six patients received 2 to 3 days of IV antibiotics, and only two patients received > 10 days of IV antibiotics. The duration of oral antibiotic treatment ranged from 76 to 412 days (median, 167 days; IQR, 142 to 214 days) [Table 1]. The subsequent resolution of main lesions on chest radiography and good overall clinical results were observed in all of the aforementioned patients (Fig 1).

[FIGURE 1 OMITTED]

Treatment of Thoracic Actinomycosis in 13 Patients Who Received Surgical Intervention Combined With Antibiotic Therapy

Combination surgical and antibiotic therapy occurred in 46% (13 of 28 patients). Exploratory thoracotomies were performed in 11 patients due to suspicion of pulmonary malignancies (n = 8) or chronic pneumonia with recurrent hemoptysis at presentation (n = 3). Two patients who had undergone surgical intervention had already received a diagnosis of thoracic actinomycosis, via either transbronchial lung biopsy or percutaneous core biopsy, before thoracotomy. These two patients underwent thoracic surgery clue to recurrent hemoptysis (patient 9, Table 2) or a slow treatment response in a ease of initially bulky disease (patient 4, Table 2). Pulmonary resections consisted of seven lobectomies, two segmentectomies, and four wedge resections. The duration of IV antibiotic treatment ranged from 3 to 17 days (median, 8 days; IQR, 5 to 13 days), and the duration of oral antibiotic treatment ranged from 0 to 534 days (median, 150 days; IQR, 3.5 to 289 days) in these 13 patients (Table 2). Five of these 13 patients (38%) received < 4 weeks of postoperative oral antibiotics. All patients experienced uneventful postoperative courses during the antibiotic therapy.

Follow-up After Completion of Antibiotic Therapy

Clinical cures were obtained at the end of antibiotic treatment in all patients. The attending physicians decided to discontinue antibiotic therapy on the basis of the findings of disappearance of both clinical symptoms and main lesions on chest radiography. The exception was one patient, who was transferred to the referring hospital for further treatment, showing signs of clinical and radiologic improvement after 5 months of oral antibiotic therapy (patient 11, Table 1). We could not confirm the treatment outcome and recurrence in this patient.

Six patients were transferred to the referring hospital after completion of antibiotic therapy. In the remaining 21 patients, follow-up duration at our hospital after completion of antibiotic treatment ranged from 4 to 72 months (median, 23 months; IQR, 9 to 44 months). There was no clinical evidence of recurrence during follow-up period in these patients.

DISCUSSION

The objective of this retrospective case series was to evaluate the duration of IV and oral antibiotics in the treatment of thoracic actinomycosis. The major findings of this study are as follows: (1) many patients with thoracic actinomycosis can be successfully treated with oral antibiotic therapy, either combined with short-term IV antibiotics, or even without IV antibiotics, after diagnosis is made by nonsurgical procedures; and (2) a substantial proportion of patients with thoracic actinomycosis can be successfully treated with < 3 months of antibiotic therapy, especially when the main lesions are removed by surgical intervention.

The clinical manifestations of thoracic actinomycosis tend to be nonspecific, and it is commonly confused with lung cancer, pulmonary tuberculosis, nocardiosis, and poorly responding pneumonia. (1-5) Once a definitive diagnosis is established, however, actinomycosis can be resolved with appropriate antibiotic therapy. (1,2,12) Until now, there are no hard-and-fast guidelines for the appropriate antibiotic treatment of thoracic actinomycosis, due both to the rarity of the disease and the consequent paucity of controlled investigations. The conventional therapy for actinomycosis involves 2 to 6 weeks of IV antibiotic therapy, followed by 6 to 12 months of oral antibiotic therapy. (1-5) In addition, the thoracic form of this disease has been considered to require a longer treatment course than other forms, such as cervicofacial actinomycosis. (5,13)

The present study demonstrated that several weeks of IV antibiotics are not always necessary for the successful treatment of thoracic actinomycosis. In 15 patients treated with antibiotics alone, only 2 patients (13%) received > 10 days of IV antibiotics. Also, in 13 patients who received surgical treatment coupled with the antibiotic treatment, only 4 patients (31%) received > 10 days of IV antibiotic treatment.

Dramatic presentation of thoracic actinomycosis, in conjunction with prominent chest pain and cutaneous fistulas which discharge sulfur granules, is rarely reported (5,11) but was frequently reported in the past. (14) With regard to the radiographic findings, previous studies (15-18) have emphasized extensive consolidations, extending to the pleura, mediastinum, and chest wall, with a tendency toward transfissural or transfascial extension. However, more recent data indicate that chest wall or rib involvement is now much less common than was previously encountered. (19,20) In our study, only one patient exhibited pleural extension with moderate pleural effusion. Transfissural or transfascial extension to the chest wall was not observed in the remaining patients. These findings suggested that such diseases are being diagnosed and treated earlier in the disease process. This phenomenon may prove to result in more favorable responses with short-term IV antibiotic therapy.

Favorable prognoses in the treatment of short-course IV antibiotic therapy, or oral antibiotic therapy alone, have been relatively well established in patients with cervicofacial actinomycosis. Several investigators (21-23) have reported that cervicofacial actinomycosis responded well to short-course oral antibiotic therapy combined with surgery. The present study is the first study, to our knowledge, supporting the effectiveness of short-term IV antibiotic therapy in the treatment of thoracic actinomycosis using a relatively large patient sample number.

The optimal duration of total antibiotic therapy for thoracic actinomycosis, as well as the optimal duration of IV antibiotic therapy, has not been thoroughly evaluated, although a total duration of 6 to 12 months is generally recommended. (1-5) Several investigators have reported relatively brief courses of antibiotic therapy being successful in cases of thoracic actinomycosis. Kinnear and MacFarlane (7) described 19 patients in whom thoracic actinomycosis was completely resolved with a median 6-week duration of antibiotic therapy (range, 1 to 24 weeks), although they did not specifically mention the durations of IV and oral antibiotic therapies utilized. Hsieh et al (8) successfully treated thoracic actinomycosis in 17 patients receiving 10 to 14 days of IV penicillin therapy followed by 3 months of oral penicillin therapy. Nine of these patients underwent surgical debulking. Skoutelis et al (9) treated one patient with 3 weeks of IV ceftriaxone followed by 3 months of oral ampicillin therapy. In addition, Dalhoff et al (10) reported the successful resolution of endobronchial actinomycosis using 2 months of antibiotic therapy.

Surgical interventions were undertaken with 13 of our 28 patients. Before penicillin and other antibiotics effected a dramatic change in modern medicine, the treatment for such conditions was principally surgical. (24) Today, even in cases of extensive pulmonary disease, medical cures should still be attempted. Nevertheless, surgical intervention is frequently performed for diagnostic purposes, as well as being used as a therapeutic adjunct. (25-27) The suspicion of malignancy is the most common indication for exploratory thoracotomy. The most common indication for therapeutic surgery is complications, including empyema, chronic sinus discharge, and hemoptysis. (25-27)

In general, it was recommended that in cases in which surgery constitutes the initial treatment, that prolonged antibiotic therapy be subsequently administered even when histology suggests complete resection. (5,28) However, the duration of postoperative antibiotic therapy has not been specifically addressed in previous studies. In our patients receiving surgical treatment in conjunction with antibiotics, the median duration of oral antibiotic therapy was 150 days (IQR, 3.5 to 289 days) and the median duration of IV antibiotics was 8 days (IQR, 5 to 13 days). In particular, three patients received no postoperative antibiotics after surgical resection, and there were no postoperative complications or recurrences. Recently, relatively brief courses of postoperative antibiotic therapy after surgical intervention have been reported by some investigators. Endo et al (26) described 13 patients with thoracic actinomycosis treated by surgical resection. Interestingly, three patients received no postoperative antibiotic therapy. In the remaining 10 patients, postoperative antibiotic treatment was continued for a median of only 1.5 months (range, 1 to 6 months). In addition, Tastepe et al (25) and Lu et al (27) reported that postoperative antibiotic therapy was completed within 2 to 3 months in their combined 21 patients with thoracic actinomycosis diagnosed after thoracotomy. Based on our experience and on previous reports, the duration of postoperative antibiotic therapy can be safely shortened if the lesions are removed completely.

The present study has several limitations, which are generally inherent in retrospective analyses. Most importantly, follow-up duration after completion of antibiotic therapy was not sufficient to fully evaluate recurrence in some cases. In addition, this study was not a randomized controlled study. Further research is required in order to address the efficacy of short course of antibiotic therapy in the treatment of thoracic actinomycosis. However, a randomized controlled study for optimal duration of IV and oral antibiotics would be difficult due to the sporadic cases of actinomycosis.

In conclusion, our study suggests that patients with thoracic actinomycosis may be candidates for individualized courses of therapy depending on the initial burden of disease, whether resectional surgery was performed, and the clinical and radiologic responses to therapy. The traditional recommendation of IV antibiotic therapy for 2 to 6 weeks followed by oral antibiotic therapy for 6 to 12 months is clearly not always necessary for all thoracic actinomycosis patients.

This work was supported by grant R11-2002-103 from the Korea Science and Engineering Foundation.

Manuscript received February 1, 2005; revision accepted April 26, 2005.

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JaeChol Choi, MD; Won-Jung Koh, MD; Tae Sung Kim, MD; Kyung Soo Lee, MD; Joungho Han, MD; Hojoong Kim, MD; and O Jung Kwon, MD

* From the Division of Pulmonary and Critical Care Medicine, Department of Medicine (Drs. Choi, Koh, H. Kim, and Kwon), Department of Radiology (Drs. T. S. Kim and Lee), and Department of Pathology (Dr. Han), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.

Correspondence to: Won-Jung Koh, MD, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-ku, Seoul 135-710, Republic of Korea; e-mail: wjkoh@smc.samsung.co.kr

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