Characteristics of Primary Pulmonary Coccidioidomycosis
During the study period, 45 patients with primary pulmonary coccidioidomycosis were enrolled; 9 withdrew consent or did not fully seroconvert, leaving 36 with probable infection for inclusion in the study (Figure 1). Of these, 27 (75%) patients remained in the study through week 24 of their illness, and 20 (56%) completed the entire 24 weeks of observation after enrollment. Median time from symptom onset to enrollment was 33 days.
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Figure 1.
Coccidioidomycosis patient enrollment and exclusions, Arizona, USA, March 1, 2010–October 31, 2012.
At the time of enrollment, 16 (44%) patients had not received antifungal therapy ( Table 1 ). Among the 20 (56%) patients who had received antifungal therapy, treatment was initiated by nonstudy medical practitioners before enrollment for 17 and by study physicians on the day of enrollment for 3. Antifungal treatment was initiated at a median of 21 days of symptoms (range 4–46 days after onset [interquartile range 11–32 days]). Of the 20 who received treatment, 18 received fluconazole at 400 mg per day for a median of 8.5 weeks (range 1.5–28.0 weeks). The median weight of patients in the treatment group was 84.8 kg (interquartile range 73–91 kg). Twenty-six patients (16 treatment, 10 nontreatment) had received empiric treatment with 1 or 2 courses of antibacterial drugs before their coccidioidomycosis diagnosis.
At enrollment, ongoing fever was more common among patients who had received treatment than among those who had not (8/20 [40%] vs. 1/16 [6.2%], respectively; p = 0.02), although other symptoms did not differ by group ( Table 1 ). At enrollment, symptom scores were higher among patients in the treatment than in the nontreatment group (median 5.5 vs. 4.0, respectively; p = 0.02).
In terms of occupation, 22 patients were employed and 3 were full-time students ( Table 1 ). The median number of whole workdays missed was 10 (range 1–28 days). One student missed 10 days of school.
At enrollment, no significant differences in serologic or radiographic findings were noted among patients in the treatment and nontreatment groups ( Table 1 ). The percentages of patients with detectable complement fixation antibody at enrollment and at 4, 12, and 24 weeks were 38% (12/32), 61% (17/28), 59% (16/27), and 23% (5/22), respectively. Peak complement fixation titers (range 1:2–1:32) occurred 4 weeks after enrollment. Radiographic scores did not differ by group; and for most patients, a unilateral radiographic abnormality <5 cm was seen. Although radiographic abnormalities improved over time, abnormalities on chest radiographs, as reflected in median scores, did not decline from 2.0 at enrollment. At 24 weeks, one-half of the patients had residual granuloma.
Table 2 summarizes primary and secondary end points of the study and shows that times to most end points were similar for both groups; for the nontreatment and the treatment groups, the median times to 50% and 100% resolution of symptoms were 9.1 and 9.9 weeks and 17.8 and 18.7 weeks, respectively. The median times to 50% resolution of fatigue were 9.8 and 12.9 weeks, respectively. Of 27 patients, 13 (48%) indicated continued fatigue by week 24. Patients in the nontreatment group returned to full-time work sooner than did those in the treatment group (5.7 vs. 8.4 weeks, respectively) (p = 0.02).
Figure 2 and Table 3 summarize symptom resolution for the 36 patients over time. Although symptom curves seemed to separate, especially from week 16 on, there was no statistical significance between these curves.
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Figure 2.
Presence of coccidioidomycosis symptoms from time of symptom onset, by treatment group, Arizona, USA, March 1, 2010–October 31, 2012 The graphs represent the percentages of patients who reported each symptom, from the time since onset of symptomatic illness. Solid lines and filled circles indicate the nontreatment group, and dashed lines and open circles indicate the treatment group. The vertical line indicates time of symptom onset. The circles to the left of the vertical line indicate the presence of symptoms at any time, including before study enrollment.
The course of convalescence was typical for 35 patients and atypical for 1 patient. This previously healthy 34-year-old White man was initially seen at an external institution for a 3-week history of fever, night sweats, dry cough, headache, and rash. Serologic test results were positive for Coccidioides spp. by enzyme immunoassay and immunodiffusion, and chest radiographs demonstrated a 3-cm nodular infiltrate; the physician prescribed a nonstandard antifungal regimen of ketoconazole at 400 mg/day. When the patient was referred to our institution (Mayo Clinic Hospital, Phoenix, AZ, USA) for possible study participation 10 days later, his symptoms were nearly resolved and ketoconazole was discontinued by the study physician. One week after enrollment, the patient experienced a severe headache; subsequent cerebrospinal fluid analysis was consistent with aseptic meningitis, presumed to be caused by Coccidioides. He was given fluconazole at 800 mg/day and promptly improved clinically. Lifelong treatment is anticipated.
Results
During the study period, 45 patients with primary pulmonary coccidioidomycosis were enrolled; 9 withdrew consent or did not fully seroconvert, leaving 36 with probable infection for inclusion in the study (Figure 1). Of these, 27 (75%) patients remained in the study through week 24 of their illness, and 20 (56%) completed the entire 24 weeks of observation after enrollment. Median time from symptom onset to enrollment was 33 days.
(Enlarge Image)
Figure 1.
Coccidioidomycosis patient enrollment and exclusions, Arizona, USA, March 1, 2010–October 31, 2012.
At the time of enrollment, 16 (44%) patients had not received antifungal therapy ( Table 1 ). Among the 20 (56%) patients who had received antifungal therapy, treatment was initiated by nonstudy medical practitioners before enrollment for 17 and by study physicians on the day of enrollment for 3. Antifungal treatment was initiated at a median of 21 days of symptoms (range 4–46 days after onset [interquartile range 11–32 days]). Of the 20 who received treatment, 18 received fluconazole at 400 mg per day for a median of 8.5 weeks (range 1.5–28.0 weeks). The median weight of patients in the treatment group was 84.8 kg (interquartile range 73–91 kg). Twenty-six patients (16 treatment, 10 nontreatment) had received empiric treatment with 1 or 2 courses of antibacterial drugs before their coccidioidomycosis diagnosis.
At enrollment, ongoing fever was more common among patients who had received treatment than among those who had not (8/20 [40%] vs. 1/16 [6.2%], respectively; p = 0.02), although other symptoms did not differ by group ( Table 1 ). At enrollment, symptom scores were higher among patients in the treatment than in the nontreatment group (median 5.5 vs. 4.0, respectively; p = 0.02).
In terms of occupation, 22 patients were employed and 3 were full-time students ( Table 1 ). The median number of whole workdays missed was 10 (range 1–28 days). One student missed 10 days of school.
At enrollment, no significant differences in serologic or radiographic findings were noted among patients in the treatment and nontreatment groups ( Table 1 ). The percentages of patients with detectable complement fixation antibody at enrollment and at 4, 12, and 24 weeks were 38% (12/32), 61% (17/28), 59% (16/27), and 23% (5/22), respectively. Peak complement fixation titers (range 1:2–1:32) occurred 4 weeks after enrollment. Radiographic scores did not differ by group; and for most patients, a unilateral radiographic abnormality <5 cm was seen. Although radiographic abnormalities improved over time, abnormalities on chest radiographs, as reflected in median scores, did not decline from 2.0 at enrollment. At 24 weeks, one-half of the patients had residual granuloma.
Table 2 summarizes primary and secondary end points of the study and shows that times to most end points were similar for both groups; for the nontreatment and the treatment groups, the median times to 50% and 100% resolution of symptoms were 9.1 and 9.9 weeks and 17.8 and 18.7 weeks, respectively. The median times to 50% resolution of fatigue were 9.8 and 12.9 weeks, respectively. Of 27 patients, 13 (48%) indicated continued fatigue by week 24. Patients in the nontreatment group returned to full-time work sooner than did those in the treatment group (5.7 vs. 8.4 weeks, respectively) (p = 0.02).
Figure 2 and Table 3 summarize symptom resolution for the 36 patients over time. Although symptom curves seemed to separate, especially from week 16 on, there was no statistical significance between these curves.
(Enlarge Image)
Figure 2.
Presence of coccidioidomycosis symptoms from time of symptom onset, by treatment group, Arizona, USA, March 1, 2010–October 31, 2012 The graphs represent the percentages of patients who reported each symptom, from the time since onset of symptomatic illness. Solid lines and filled circles indicate the nontreatment group, and dashed lines and open circles indicate the treatment group. The vertical line indicates time of symptom onset. The circles to the left of the vertical line indicate the presence of symptoms at any time, including before study enrollment.
The course of convalescence was typical for 35 patients and atypical for 1 patient. This previously healthy 34-year-old White man was initially seen at an external institution for a 3-week history of fever, night sweats, dry cough, headache, and rash. Serologic test results were positive for Coccidioides spp. by enzyme immunoassay and immunodiffusion, and chest radiographs demonstrated a 3-cm nodular infiltrate; the physician prescribed a nonstandard antifungal regimen of ketoconazole at 400 mg/day. When the patient was referred to our institution (Mayo Clinic Hospital, Phoenix, AZ, USA) for possible study participation 10 days later, his symptoms were nearly resolved and ketoconazole was discontinued by the study physician. One week after enrollment, the patient experienced a severe headache; subsequent cerebrospinal fluid analysis was consistent with aseptic meningitis, presumed to be caused by Coccidioides. He was given fluconazole at 800 mg/day and promptly improved clinically. Lifelong treatment is anticipated.