Efficacy and safety of moxifloxacin for community-acquired bacterial pneumonia based on pharmacokinetic analysis.

Moxifloxacin is a respiratory quinolone that is expected to be useful for treating community-acquired bacterial pneumonia, but few clinical studies and not a detailed evaluation of its pharmacokinetics have been conducted in Japan in patients with pneumonia. We assessed the efficacy and safety of moxifloxacin in 18 patients with community-acquired bacterial pneumonia using pharmacokinetic-pharmacodynamic analysis. There was significant improvement in body temperature, white blood cell count, C-reactive protein, and chest X-ray score on day 3 of moxifloxacin treatment, which persisted until the completion of treatment (all p < 0.05). Nine strains, including Streptococcus pneumoniae, Moraxella catarrhalis, Haemophilus influenzae, and Enterobacter cloacae, were isolated from sputum cultures of nine patients. The isolated strains were eradicated by moxifloxacin. The mean area under the concentration-time curve from 0 to 24 hours [AUC(0-24 h) (AUC(0-24 h,ss))], maximum plasma concentration (C(max)), and trough plasma level (C(trough)) of moxifloxacin at steady state was 52.0 µg h/ml, 4.5, and 0.9 µg/ml, respectively. Mean AUC(0-24 h,ss)/mimimum inhibitory concentration (MIC), and C(max)/MIC ratios for patients in whom MICs of moxifloxacin were determined for pathogenic bacteria were 723 and 62, respectively. The median AUC(0-24 h,ss)/MIC and C(max)/MIC ratios (based on Monte Carlo simulation employing MICs for 257 strains of S. pneumoniae collected during a respiratory infection survey by the Japanese Society of Chemotherapy in 2007) were 209.56 and 17.88, respectively. Thus, when the target for the AUC/MIC ratio was set at ≥30 and that for the C(max)/MIC ratio at ≥5, the achievement rate for these two parameters was 97.36% and 96.71%, respectively. Two patients (11%) experienced three adverse effects [one nausea, another increased aspartate aminotransferase (AST) and alanine aminotransferase (ALT)], but the events were not serious. Based on these results, moxifloxacin (400 mg once daily) was considered useful for treating community-acquired bacterial pneumonia and is expected to show excellent efficacy and safety as well as suppressing the emergence of resistance.

[Case of SAPHO syndrome with significant sternocostoclavicular hyperostosis].

A 59-year-old man with hypertension developed general fatigue, fever, and precordialgia in early March 2007. An antibacterial agent was intravenously administered; however, no improvement in his symptoms or laboratory findings was observed. He had acne and pustulosis, and radiographs and CT of the chest revealed sternocostoclavicular hyperostosis. As a result, the diagnosis was revised to SAPHO syndrome, and he improved with steroid administration. SAPHO syndrome is a condition that is rarely found at the initial examination in the Department of Internal Medicine. We report a case with a discussion of the literature.

Clinical features of Proteus mirabilis pneumonia.

In this study, we clinically reviewed 13 patients with Proteus mirabilis pneumonia who were admitted for treatment to Kawasaki Medical School Kawasaki Hospital, Okayama, Japan, between April 2006 and July 2009. Clinical features were retrospectively reviewed. Results showed that: (1) hospital-acquired pneumonia occurred in elderly patients with underlying diseases such as cerebrovascular disease; (2) some patients had complications of urinary tract infection due to P. mirabilis; (3) preadministration of antibacterial agents did not become a risk factor; (4) resistance for levofloxacin (LVFX) was observed; (5) prognosis was comparatively good (effective rate 84.7%).

Clinical features of Escherichia coli pneumonia.

Escherichia coli pneumonia was clinically reviewed. Twenty-two patients with E. coli pneumonia were admitted for treatment to Kawasaki Medical School Kawasaki Hospital, between January 2006 and December 2008. Clinical features were retrospectively reviewed. Results showed that: (1) hospital-acquired pneumonia occurred in elderly patients with underlying diseases, such as cerebrovascular disease, diabetes mellitus, or chronic obstructive pulmonary disease; (2) more patients had complications of urinary-tract infection or alimentary infection due to E. coli; (3) previous administration of antibacterial agents did not become a risk factor; (4) resistance to ampicillin (ABPC) and levofloxacin (LVFX) was observed; and (5) mortality was 22.7%.

[A case of miliary tuberculosis difficult to distinguish from metastatic lung cancer].

We report a case of the coexistence of pulmonary tuberculosis and lung cancer maked a wrong diagnosis of lung cancer and metastatic lung carcinoma. The patient was a 80-years-old woman who had ascites and anorexia and decreased weight. Chest CT film showed a mass shadow in the right S, and infiltrative shadows on bilateral lung fields. FDG-PET revealed the tumor in the right lower lung field and many infiltrative shadows in all lung fields, and showed that FDG accumulated diffusely along the peritoneum. We made a diagnosis of lung cancer and metastatic lung carcinoma. However we obtained a diagnosis of coexisting of pulmonary tuberclosis and lung cancer autopsy. When the patient has a shadow suggestive of lung tumor shadow with many infiltrative shadows, we tend to make a diagnosis of lung cancer and metastatic lung carcinoma. We saw the importance of a postmortem examination in a new light.

Procalcitonin and severity of community-acquired pneumonia.

The purpose of this study was to clarify the relationship between procalcitonin and the severity and prognosis of community-acquired pneumonia. The subjects were 162 patients with community-acquired pneumonia (disease severity, mild, 39 patients; moderate, 81 patients; severe, 37 patients; and super severe, 5 patients) in whom we examined the serum procalcitonin concentration at the start of treatment; we determined the relationship of procalcitonin status with disease severity and prognosis. The results showed that procalcitonin was positive in 12.8% of the patients with mild disease, 27.1% of the patients with moderate disease, 59.5% of the patients with severe disease, and 80.0% of the patients with super severe disease. The mortality of procalcitonin-positive patients was 37.7%, whereas that of the procalcitonin-negative patients was 12.8%. Based on the above findings, it is concluded that the more severe the community-acquired pneumonia, the higher is the positivity rate for procalcitonin, and the prognosis in procalcitonin-positive patients is worse than that in procalcitonin-negative patients.

[Clinical effects of continuous infusion and intermittent infusion of meropenem on bacterial pneumonia in the elderly].

We compared the clinical effects of continuous infusion and intermittent infusion of meropenem (MEPM) on bacterial pneumonia in the elderly. The subjects were elderly patients (over 65) with moderate community-acquired bacterial pneumonia whose performance status was 3 or 4. They were randomly divided into an intermittent group (0.5 g MEPM was infused morning and evening) and a continuous infusion group (1.0 g/day over 24 hours was infused continuously), and the clinical effects were reviewed prospectively. Clinical efficacy on the third day was 64.0% in the intermittent infusion group and 72.0% in the continuous infusion group, and the overall clinical efficacy was 76.0% in the intermittent infusion group and 80.0% in the continuous infusion group. Administration periods were 13.2 +/- 5.7 days in the intermittent infusion group and 12.1 +/- 4.5 days in the continuous infusion group. These results show no statistically significant difference, and suggest that continuous infusion of MEPM did not have better clinical effect than intermittent administration twice a day in the treatment of elderly patients with moderate community-acquired bacterial pneumonia.

Evaluation of clinical dosage of gatifloxacin for respiratory tract infections in elderly patients based on pharmacokinetics/pharmacodynamics (PK/PD).

The efficacy and safety of gatifloxacin (GFLX) was evaluated for elderly patients with respiratory infections. Each patient received one-half (100 mg b.i.d.) or one-quarter (100 mg q.d.) of the conventional dosage of 200 mg b.i.d., after a tentative clinical dosage for GFLX was estimated based on the patient's age and body weight. The subjects were 34 patients aged 65 years or older with mild to moderate acute bronchitis, pneumonia, or chronic respiratory tract infections. The serum concentration of GFLX was measured for each patient, and population and pharmacokinetic (PPK) analysis was performed, using the Bayesian method, to calculate the AUC and maximum drug concentration (Cmax). The overall efficacy rate of GFLX for 33 patients was 87.9% (29/33 patients). GFLX was effective for 75.0% (6/8 patients) in the 100-mg dosage group and 92.0% (23/25 patients) in the 200-mg dosage group. The clinical efficacy was 90.0% (9/10 patients) for acute bronchitis, 86.7% (13/15 patients) for pneumonia, and 87.5% (7/8 patients) for chronic respiratory tract infections. The bacterial eradication rate was 85.7% (12/14 patients). No adverse events or laboratory abnormalities were observed. The AUC values were 11.2-37.5 microg.h/ml and 12.7-111 microg.h/ml for the 100-mg and 200-mg dosage groups, respectively, and the Cmax values were 1.28-3.02 microg/ml and 0.72-6.35 microg/ml, respectively, for the two groups. These results suggest that the dosage of GFLX examined in this study is clinically useful in elderly patients aged 65 or older with acute bronchitis, pneumonia, or chronic respiratory tract infections. The results of PPK analysis with the dosage management also support the efficacy of GFLX.

[Q fever in hospital-acquired pneumonia].

We studied the effects of Q fever in hospital-acquired pneumonia. The subjects consisted of 121 cases with hospital-acquired pneumonia treated during the period from December 2004 till June 2007. Q fever was diagnosed using a PanBio Coxiella burnetii ELISA test kit. There were no patients with acute infection by Coxiella burnetii. It is concluded that C. burnetii cannot induce onset of hospital-acquired pneumonia.

[Clinical effects of intravenous ciprofloxacin on community-acquired pneumonia with positive Immunocard Mycoplasma test results].

We studied the clinical effects of intravenous ciprofloxacin (CPFX) on community-acquired pneumonia in patients with positive Immunocard Mycoplasma test results. The subjects were 35 patients (59.4 +/- 24.8 years old) with community-acquired pneumonia with positive Immunocard Mycoplasma test results. We infused CPFX 300mg copy intravenously twice daily for 3-14 days. It was effective in 33 of 35 patients, with an efficacy rate of 94.3%. Adverse reactions consisted of itching in 2 patients, malaise in 2 patients, drug eruption in 1 patient, elevation of GPT in 1 patient and elevation of BUN in 1 patient, but all were mild. We conclude that intravenous CPFX is useful for community-acquired pneumonia in case with positive Immunocard Mycoplasma test results.

[Study of the cases with multidrug-resistant Pseudomonas aeruginosa by sputum culture].

We evaluated the clinical features of multidrug-resistant Pseudomonas aeruginosa cases determined by sputum culture between April, 2005 and December, 2006. The clinical features of most cases were: (1) pneumonia in the elderly with cerebrovascular diseases, (2) previous administration of carbapenems and antipseudomonal cephems, (3) PIPC, CAZ and ISP sensitve MDRP, (4) MRSA was isolated concurrently, (5) not necessary of therapy against MDRP, (6) good outcome.

[Case of multiple intrapulmonary lymph nodes].

A 45-year-old man who had hypertension, hyperthyroidism, and bronchial asthma was admitted to our hospital because of a low-grade fever and chest pain. The physical findings and laboratory data were almost all within normal limits except for evidence of mild inflammation and liver dysfunction. The chest X-ray findings seemed normal, but a computed tomography (CT) scan showed multiple nodules in both lower lung fields. We suspected the cryptococcosis or lung cancer. Biopsy by video-assisted thoracoscopic surgery (VATS) yielded a diagnosis of multiple intrapulmonary lymph nodes. In cases with the above radiologic findings, careful attention should be paid to making the differential diagnosis between intrapulmonary lymph nodes and primary lung cancer. The promotion of diagnostic imaging and advances in techniques have made it easier to identify small peripheral nodules in the lungs, and we now know of their existence. Solitary intrapulmonary lymph nodes are encountered frequently, but multiple or increasing numbers of nodes, as in our case, are very rare. Moreover, because cases with elevated CEA levels have been reported, differentiation from lung cancer appears to be important.

[Positive phase periods of ImmunoCard Mycoplasma tests].

We evaluated the positive phase period of ImmunoCard Mycoplasma tests. The subjects were 74 penumonia patients (male : 38, female : 36, 17-94 years old) with positive ImmunoCard Mycoplasma tests. ImmunoCard Mycoplasma tests were performed every week for 8 weeks later, then every 4 weeks until negative conversion. The positive phase period was within a week in 30 of 74 patients (40.5%) and within 4 weeks in 52 patients (70.3%). In each generation the positive phase period of the most patients was within a week. The positive phase period of the elderly had no tendency to be longer than that of the young patients. These results indicated that about half of the patients with positive ImmunoCard Mycoplasma tests showed Mycoplasma infection which occurred within the past 1 week.

[Testing for Mycoplasma pneumonia using the ImmunoCard Mycoplasma rapid test].

We evaluated the effectiveness of ImmunoCard Mycoplasma rapid tests in all patients admitted with community-acquired pneumonia (CAP) between January, 2004 and December, 2005. ImmunoCard Mycoplasma rapid tests were performed on the 1st day of admission and we analyzed the frequency of positive cases among CAP cases according to month and age. A total of 82 of 270 (33.7%) and 41 of 257 (16.0%) were positive among CAP cases in 2004 and 2005, respectively. More positive cases were seen between spring and early summer and in cases aged 70 years or more, especially those over 80 years old. These results indicated that further evaluation is required among positive cases in elder group.