Antipyretic and analgesic effects of zaltoprofen for the treatment of acute upper respiratory tract infection: verification of a noninferiority hypothesis using loxoprofen sodium.

A multicenter, placebo-controlled, double-dummy, randomized, parallel-group, double-blind study was conducted to verify the hypothesis of noninferiority for single-dose administration of zaltoprofen 160 mg, a nonsteroidal anti-inflammatory drug, compared with loxoprofen sodium 60 mg (loxoprofen), in terms of antipyretic and analgesic effects in patients with acute upper respiratory tract infection. The eligible 330 patients were assigned to one of 3 groups: zaltoprofen 160 mg, loxoprofen 60 mg and placebo. The analysis set consisted of 322 patients. Antipyretic effects were assessed by measuring body temperature, and analgesic effects were evaluated using a visual analog scale (VAS) for 4 h under the control of study staff. A detection kit for influenza virus A and B antigens was used to determine the presence of influenza virus infection. Compared with immediately before administration and with the placebo group, significant decreases in body temperature and summary VAS pain scores were noted in both the zaltoprofen and loxoprofen groups at 4 h after drug administration. Based on the degree of decrease in body temperature and the summary VAS pain scores up to 4 h after administration, noninferiority in terms of antipyretic and analgesic effects of zaltoprofen compared with those of loxoprofen was confirmed after single administration. Similar antipyretic and analgesic effects were also confirmed in influenza virus antigen-positive patients (73 patients). No clinical concerns were identified regarding safety. Zaltoprofen and loxoprofen are confirmed to be safe and useful for patients with acute upper respiratory tract infection, including those with influenza infection.

A double-blind study of zaltoprofen for the treatment of upper respiratory tract infection.

We conducted a double-blind study to evaluate the antipyretic and analgesic effects of a single administration of zaltoprofen, a nonsteroidal anti-inflammatory drug, in patients with acute upper respiratory tract infection. 170 patients were assigned to one of the 3 treatment groups (80, 160 mg, placebo). Changes over time of body temperature and the visual analog scale score of pain were measured under the supervision of the study staff at the participating medical institutions. A significant decrease in body temperature from the baseline value was noted at all measurement points from 0.5 to 6 h after drug administration in the zaltoprofen groups. The lowest temperature during the observation period was recorded between 3 and 4 h, and the body temperature tended to rise at 6 h. No significant decrease in body temperature was noted at any time during the observation period in the placebo group. A significant decrease in pain scores from the baseline was noted at all measurement points in the zaltoprofen groups, and the decrease was maintained even at 6 h. An analgesic effect but no antipyretic effect was observed in the placebo group.

Variation in the attachment of Streptococcus pneumoniae to human pharyngeal epithelial cells after treatment with S-carboxymethylcysteine.

S-carboxymethylcysteine (S-CMC) is a mucolytic agent that can prevent respiratory infection by decreasing the attachment of respiratory pathogens to human pharyngeal epithelial cells (HPECs). Streptococcus pneumoniae is a major cause of respiratory infections. A previous study revealed that treatment of S. pneumoniae with S-CMC caused a decrease in the attachment of this bacterium to HPECs. In the present study we found that the effect of S-CMC varied according to hosts and strains. S-CMC treatment altered the surface structure of S. pneumoniae, resulting in a decrease of attachment, without affecting the virulence of the bacteria.

Clinical and microbiological characteristics of community-acquired pneumonia among human immunodeficiency virus-infected patients in northern Thailand.

Human immunodeficiency virus (HIV) infections are prevalent in Thailand. However, the clinical and microbiological characteristics of community-acquired pneumonia (CAP) in such patients are not completely clear at present. In the present study, we analyzed the characteristics of CAP in 191 HIV-infected patients (192 episodes, 130 males and 61 females, mean age 32.9 years, range: 20-62) who had been admitted to Nakornping Hospital in northern Thailand between December 1996 and January 2002. The mean peripheral blood CD4 lymphocyte count was 68.5/mm3 (range: 0-791). The most common organisms detected in the blood of the subjects were as follows: Penicillium marneffei, 13, Salmonella spp., 5, Cryptococcus neoformans, 4, Staphylococcus aureus, 3, and Rhodococcus equi, 3, and the most common organisms detected in sputum included Haemophilus influenzae, 38, P. marneffei, 10, Streptococcus pneumoniae, 10, R. equi, 9, and S. aureus, 9. Life-threatening meningitis in 5 (cryptococcal in 3 and tuberculous in 2), pneumothorax in 2, and tuberculous lymphadenitis in 1 were also noted, resulting in 21 fatalities (10.9%). The mean peripheral blood CD4 lymphocyte count for cases in which the subject died was 74.8/mm3 (range: 0-340). Logistic regression analysis demonstrated that high age (odds ratio of over 40 years: 15.62) and R. equi infection (odds ratio: 8.14) are related to death of HIV-infected patients with CAP. The above findings indicate that various types of organisms, including mixed organisms, cause CAP in HIV-infected patients in northern Thailand, and high age and R. equi infection seem to be risk factors for death.

Induction of opsonophagocytic killing activity with pneumococcal conjugate vaccine in human immunodeficiency virus-infected Ugandan adults.

The levels of IgG determined by ELISA may have limited relevance in human immunodeficiency virus (HIV)-infected adults because of non-functional antibodies. 58 HIV-1-infected and 29 HIV-uninfected Ugandan adults were immunized with conjugate vaccine (CV) followed by polysaccharide vaccine (PV) after a 2-month interval, and the opsonophagocytic killing (OPK) titers against serotype 4 or 14 pneumococcal strains as well as the levels of serotype-specific IgG in sera were determined. Significant increases were found in the OPK titers and IgG levels for both serotypes after CV vaccination irrespective of HIV status. Increases in IgG levels and OPK titers were largely dependent on the CD4(+) cell counts, except for increases in the IgG levels for serotype 4. The proportions with serum OPK titer equal to or greater than 8 were 0-4.3% for serotype 4 and 26.7-42.9% for serotype 14 before vaccination, but the proportions increased up to 43.3-86.2% for serotype 4 and 63.3-96.6% for serotype 14 in all three groups 2 months after CV vaccination. The serum OPK titers remained at levels higher than the pre-vaccination level for at least 8 months after CV vaccination. A single dose of CV could afford some protective immunity in HIV-infected African adults before the introduction of antiretroviral therapy.

Additive effect of pneumococcal vaccine and influenza vaccine on acute exacerbation in patients with chronic lung disease.

To determine the clinical efficacy of combined vaccination with 23-valent pneumococcal vaccine (PV) and influenza vaccine (IV) against pneumonia and acute exacerbation of chronic lung diseases (CLD), we conducted an open-label, randomized, controlled study among 167 adults with CLD over a 2-year period. Subjects were randomly assigned to a PV+IV group (n=87) or an IV group (n=80). The number of patients with CLD experiencing infectious acute exacerbation (P=0.022), but not pneumonia (P=0.284), was significantly lower in the PV+IV group compared with the IV group. When these subjects were divided into subgroups, an additive effect of PV with IV in preventing infectious acute exacerbation was significant only in patients with chronic obstructive pulmonary diseases (P=0.037). In patients with CLD, the Kaplan-Meier survival curves demonstrated a significant difference for infectious acute exacerbation (P=0.016) between the two groups. An additive effect of PV with IV on infectious acute exacerbation was found during the first year after vaccination (P=0.019), but not during the second year (P=0.342), and was associated with serotype-specific immune response in sera of these patients who used PV during the same period.

Drug-resistant pneumococci in children with acute lower respiratory infections in Vietnam.

BACKGROUND: Acute lower respiratory infections (ALRI), primarily pneumonia, are the leading cause of death in children under 5 years of age. Most of these deaths occur in Africa and southeast Asia. Increasing rates of drug resistance in pneumococcal strains emphasize the necessity of prevention of pneumococcal vaccines. The aim of the present study was to determine the frequency of drug resistance and the distribution of serotype of pneumococcal strains isolated from pediatric patients with ALRI in Vietnam. METHODS: Two hundred and twenty pediatric patients with ALRI under 5 years of age were enrolled in Hanoi, Vietnam between 2001 and 2002. Bacterial pathogens with a heavy growth (10(6) c.f.u./mL) were isolated from nasopharyngeal secretions on quantitative culture. Fifty-three pneumococcal strains isolated from the nasopharynx of pediatric patients were examined for antibiotic susceptibility including drug-resistant genes and serotyping. RESULTS: A total of 73.6% of pneumococcal strains were genotypic penicillin-resistant Streptococcus pnemoniae (gPRSP), possessing altered penicillin-binding protein genes pbp 1a + 2x + 2b; 67.9% of these strains were gPRSP and simultaneously had the ermB gene, which is responsible for high resistance to erythromycin. The majority of gPRSP strains were serotype 19F or 23F. CONCLUSION: gPRSP strains with serotype 19F or 23F are highly prevalent among pediatric patients with ALRI under 5 years of age in Hanoi, Vietnam.

Increased rates of intense nasopharyngeal bacterial colonization of Vietnamese children with radiological pneumonia.

Acute lower respiratory infection (ALRI), primarily pneumonia, is the leading cause of death in children under the age of five. Bacterial ALRI is preceded by asymptomatic bacterial colonization. Bacterial colonization, therefore, may have an important role in the development of pneumonia in children. This case-control study was conducted in order to determine if intense bacterial colonization was increased in the nasopharynx of pediatric patients with ALRI. One hundred-sixty four pediatric patients with ALRI and 70 healthy children < 5 years of age were enrolled in Hanoi, Vietnam between 2001 and 2002. Bacterial pathogens were isolated from nasopharyngeal secretions and quantitatively cultured. Of 164 patients, 91 were diagnosed as having radiological pneumonia (PN group) and 73 as having acute bronchitis (AB group). Intense growth of any bacterial pathogen (>or= 10(6) colony-forming units/ml) was highest in the PN group (49.4%), followed by the AB group (28.8%), with healthy children having the lowest (17.1%). Patients with intense bacterial growth were more likely to develop pneumonia, but not acute bronchitis, than were patients with light or no bacterial growth. The results of this case-control study suggest that the vertical spread of intense bacterial pathogens colonized in the nasopharynx to the lower airway leads to bacterial pneumonia in children under the age of five.

Comparative immune responses of patients with chronic pulmonary diseases during the 2-year period after pneumococcal vaccination.

Antibody responses to a 23-valent pneumococcal vaccine for Streptococcus pneumoniae serotypes 6B, 14, 19F, and 23F in 84 patients with chronic pulmonary diseases over a 2-year period after vaccination were examined by using a third-generation enzyme-linked immunosorbent assay. Of these patients, 28 (31%) were low responders who had developed increases of at least twofold in the levels of serotype-specific immunoglobulin G (IgG) in sera for none of the four serotypes at 1 month after vaccination. Although no specific clinical features of low responders were evident, their prevaccination levels of IgG for all serotypes were higher than those of responders. In responders, the levels of IgG specific for serotypes 14 and 23F in sera were greatly increased 1 month after vaccination and those specific for serotypes 6B and 19F were moderately increased. In contrast, no significant increases in the levels of IgG specific for serotypes 6B, 19F, and 23F in the low responders during the same period were found, but the levels of IgG specific for serotype 14 did increase. Although a rapid decline in the levels of IgG for all serotypes in responders between 1 month and 6 months after vaccination was found, the levels of IgG specific for serotypes 14 and 23F in sera remained higher than the prevaccination levels for at least 2 years after vaccination. These data suggest the need for the revaccination of responders but not low responders among patients with chronic pulmonary diseases. Revaccination as early as 3 years postvaccination is recommended for responders to increase the reduced levels of IgG in sera, especially those specific for the weak vaccine antigens.

[A case of pulmonary infection due to Mycobacterium chelonae treated by lobectomy after a long course of oral antimicrobial agents].

Small nodular shadows were pointed out in right upper lobe and middle lobe on the chest radiograph of a 60-year-old woman in 1992. Mycobacterium chelonae was isolated from bronchoalveolar lavage (BAL) fluid in 1994. Long term antimicrobial chemotherapy with rifampicin, ethambutol, clarithromycin and quinolone antibiotics was then started. The chest radiograph, however, revealed infiltration in the right upper and middle lobes and the isolated strain was found to be resistant to antimicrobials in 2000. She therefore underwent right upper and middle bilobectomy. She had no relapse of infection postoperatively. Surgical treatment should be considered for pulmonary infection due to Mycobacterium chelonae resistant to multiple antimicrobial chemotherapy.

Sulfatide and its synthetic analogues recognition by Moraxella catarrhalis.

Moraxella catarrhalis is one of the major pathogens of respiratory and middle ear infections. Attachment of this bacterium to the surface of human pharyngeal epithelial cells is the first step in the pathogenesis of infections. This study revealed that sulfatide might act as a binding molecule for the attachment of M. catarrhalis to human pharyngeal epithelial cells. Furthermore, six different synthetic sulfatides were found to inhibit the attachment of M. catarrhalis significantly at an optimum concentration of 10 microg/ml. Synthetic sulfatides may have the potential to be used as a therapy to prevent M. catarrhalis infections.

Dynamics of dendritic cell migration and the subsequent induction of protective immunity in the lung after repeated airway challenges by nontypeable Haemophilus influenzae outer membrane protein.

To determine the dynamics of dendritic cell (DCs) migration and their role in recurrent infections by nontypeable Haemophilus influenzae (NTHi), the migration of mature DC into pulmonary lymph nodes (LN) and the development of a P6-specific immune response and bacterial clearance in the lung were examined after repeated airway challenges with outer membrane protein (OMP) at 1-week intervals in mice. Although the migration of mature DC into the pulmonary LN is attenuated after repeated airway challenge with OMP, the in vitro P6-specific T cell proliferation in the cultured pulmonary LN cells was enhanced and was subsequently linked to the development of P6-specific IgA production and the development of protective immunity in the airway of mice.

Drug-resistant genes and serotypes of pneumococcal strains of community-acquired pneumonia among adults in Japan.

BACKGROUND: A high frequency of drug-resistant pneumococci has been reported in Asian countries. Few data on the drug-resistance or serotype of pneumococcal strains responsible for community-acquired pneumonia (CAP), however, are available for the past two decades in Japan. METHODOLOGY: Susceptibility to antibiotics and the genotype of antibiotic-resistant genes and serotypes of Streptococcus pneumoniae isolates from 114 adult patients with CAP were examined in a nationwide study in Japan between 2001 and 2003. RESULTS: Most of the cases were non-bacteraemic pneumonia and the case fatality rate was 4.4%. The most frequent genotype of the pbp gene was pbp1a + 2x + 2b (gPRSP; 36.8%) followed by pbp 2x (28.1%) and of the macrolide-resistant gene, it was ermB (50.0%). The most common serotype was 19F (29.1%), followed by serotype 23F (13.2%), 6B (12.3%) and 3 (11.4%). The coverage of serotypes of isolates by a 23-valent pneumococcal polysaccharide vaccine (PPV) would be 82.5% in these patients with CAP. Most of strains with serotypes 19F and 23F were gPRSP. A cluster of serotype 3 strains associated with the pbp 2x and ermB gene was also noted. CONCLUSION: A high frequency of altered pbp gene mutations or of macrolide-related genes and a high serotype coverage by the 23-valent PPV found in our study of pneumococcal pneumonia facilitates attempts to increase the coverage rate of the 23-valent PPV in adults older than 65 years in Japan.

Significant reduction of nosocomial pneumonia after introduction of disinfection of upper airways using povidone-iodine in geriatric wards.

We investigated the efficacy of disinfection of the upper airway using povidone-iodine against nosocomial pneumonia in geriatric wards. Cases of nosocomial pneumonia were retrospectively analyzed between January 1991 and March 1995 in geriatric wards (190 beds). Moreover, the relationship concerning methicillin-resistant Staphylococcus aureus (MRSA) isolates between patient and environment was investigated using pulsed-field gel electrophoresis (PFGE) with the SmaI restriction enzyme. The incidence of nosocomial pneumonia decreased significantly (p < 0.05). Major causative organisms of nosocomial pneumonia were MRSA and Pseudomonas aeruginosa, which significantly decreased. PFGE studies showed that the patterns of MRSA isolates show a strong association between patient and environment. Our study indicates that disinfection of the upper airways by povidone-iodine is very important in the prevention of nosocomial pneumonia in geriatric wards.

Role of lipooligosaccharide in the attachment of Moraxella catarrhalis to human pharyngeal epithelial cells.

The goal of this study was to determine the role of lipooligosaccharide in the attachment of Moraxella catarrhalis to human pharyngeal epithelial cells. Strain 2951 and its P(k) mutant strain 2951 galE were used in this study. This study suggests that the P(k) epitope of LOS is not an adhesin for M. catarrhalis, but plays a crucial role by its surface charge in the initial stage of attachment.

Comparison of clinical features and hematologic abnormalities between dengue fever and dengue hemorrhagic fever among children in the Philippines.

To demonstrate the differences of clinical features and hematologic abnormalities between dengue fever (DF) and dengue hemorrhagic fever (DHF), 359 pediatric patients admitted St. Luke's Medical Center in Quezon City, between 1999 and 2001 in Metro Manila, and adjoining provinces the Philippines, with a laboratory-confirmed dengue virus infection were evaluated. One third of the patients had DHF, and most of these patients were without shock. Restlessness, epistaxis, and abdominal pain were more associated with DHF. The platelet count was significantly lower in the DHF group than in the DF group before and after defervescence. In the DHF patients, the hematocrit was significantly increased before defervescence, and decreased the day after due to administration of intravenous fluid. Coagulation abnormalities associated with most DHF patients were thrombocytopenia and an increased fibrinolysis, but not disseminated intravascular coagulation. We present recent data on readily obtained clinical and laboratory data that can be used for early diagnosis and consequently earlier appropriate treatment of dengue virus infections.