The association of body mass index, waist and hip circumference, and waist-hip ratio with Chlamydia pneumoniae IgG antibodies and high-sensitive C-reactive protein at 31 years of age in Northern Finland Birth Cohort 1966.

BACKGROUND: Viruses and bacteria like Chlamydia pneumoniae and Helicobacter pylori have been suggested to have a role in pathogenesis of overweight and obesity. OBJECTIVE: We studied whether C. pneumoniae-specific IgG antibodies are associated with elevated body mass index (BMI), waist and hip circumference, and/or waist-hip ratio (WHR), and whether the risk is more pronounced in the simultaneous presence of an ongoing inflammation as measured by elevated high-sensitive C-reactive protein (hsCRP) levels. SUBJECTS AND METHODS: Our study population was derived from the Northern Finland Birth Cohort 1966 (NFBC1966), a general population sample of 12,058 live-born children. This cross-sectional study consisted of 5044 persons at 31 years of age. Serum C. pneumoniae IgG titers were measured by microimmunofluorescence test, and hsCRP levels by immunoenzymometric assay. RESULTS: C. pneumoniae IgG positivity (titer ≥ 32), both alone and jointly with elevated hsCRP (≥ 1.64 mg l(-1), an upper quartile), was found to significantly associate with elevated BMI in the whole study population and with elevated hip and waist circumference in women, yet no association with WHR was seen. The analyses were adjusted for sex (when appropriate), smoking, socioeconomic position, glucose, insulin, high- and low-density lipoprotein cholesterols, triglycerides, leukocytes and pulse pressure. CONCLUSION: These findings suggest that especially in women, persistent C. pneumoniae infection may be associated with overweight/obesity, independently of more traditional risk factors.

Interleukin-6-174 G/C promoter polymorphism is associated with persistence of Chlamydia pneumoniae antibodies in young men.

A promoter polymorphism -174 G/C in the inflammatory cytokine interleukin-6 (IL-6) gene has been associated with differences in serum IL-6 levels and a risk for inflammatory conditions, such as cardiovascular diseases. We investigated whether this polymorphism is associated with Chlamydia pneumoniae, a common causative agent of respiratory infection with tendency for persistent infections, in 867 Finnish military recruits. IgG seropositivity in arrival and departure serum samples during 6-12 months of military service was considered as persistence of antibodies and a possible prolonged or chronic infection. The -174C allele was significantly associated with IgG seropositivity (P = 0.0002) and the persistence of IgG antibodies (P = 0.0002) as well as with slightly elevated C-reactive protein (CRP) levels (P = 0.003). In addition, the association was stronger when persistent C. pneumoniae antibodies were present together with elevated CRP than when either of them was positive alone (OR; 95% CI: 3.45; 2.00-5.98 and 1.41; 1.00-1.99, respectively). Our data suggest that IL-6 -174 G/C polymorphism is associated with persistence of C. pneumoniae antibodies and may be linked to the chronic or prolonged infection with systemic low-grade inflammation.

Periodontopathogen- and host-derived immune response in acute coronary syndrome.

Owing to molecular mimicry, periodontal pathogen carriage may result in a systemic cross-reactive immune response with the host. The analyses were performed to investigate if serum antibody levels to human heat shock protein 60 (HSP60) are associated with the antibody levels and salivary carriage of two periodontal pathogens, Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis, as well as with the dental status in patients with acute coronary syndrome (ACS). ACS patients (n = 141) were monitored at baseline when entering to hospital, and after 1 week, 3 months and 1 year. Periodontal status was recorded by dental radiographs, and A. actinomycetemcomitans and P. gingivalis were detected by PCR from saliva at baseline. Serum IgG and IgA antibody levels were determined at all time points. All antibody levels remained quite stable during the follow-up. Serum IgG-class antibody levels to A. actinomycetemcomitans and HSP60 had a strong positive correlation with each other at all time points (r∼0.4, P < 0.05). Mean serum IgG antibody levels to HSP60 were significantly higher in the A. actinomycetemcomitans IgG- and IgA-seropositive than in the seronegative patients, but did not differ between the pathogen carriers compared to the non-carriers. HSP60 antibody levels did not differ significantly between the edentulous, non-periodontitis and periodontitis patients. Despite the observed cross-reactivity in the systemic IgG-class antibody response to HSP60 and A. actinomycetemcomitans, the pathogen carriage in saliva or the periodontal status did not affect the HSP60 antibody levels in ACS patients.

Elevated MMP-8 and decreased myeloperoxidase concentrations associate significantly with the risk for peripheral atherosclerosis disease and abdominal aortic aneurysm.

Matrix metalloproteinases are responsible for degradation and remodelling of extracellular matrix and exert important roles in initiation and progression of inflammatory diseases. We aimed to examine the role of Matrix metalloproteinases (MMPs) and their regulators in degenerative arterial diseases. Serum samples were collected from patients with arterial disease (n = 126), who underwent surgery because of symptomatic aorto-occlusive disease (AOD, n = 18), carotid artery stenosis (n = 67) or abdominal arotic aneurysm (n = 41). Serum MMP-1, MMP-8, MMP-13, TIMP-1, myeloperoxidase (MPO) and neutrophil elastase (HNE) concentrations were determined by ELISA, and the molar ratio of MMP-8 and TIMP-1 was calculated. To get reference values, the determinations were done on samples of healthy blood donors (n = 100). In univariate analyses, the patients had higher MMP-8 (P < 0.001), TIMP-1 (P = 0.045), and MMP-8/TIMP-1 (P < 0.001), and lower MPO (P < 0.001) when compared with the blood donors. All three subgroups had higher MMP-8 (P < 0.001) and MMP-8/TIMP-1 (P < 0.001), and lower MPO (P < 0.01, except AOD) levels when compared with the references. In multiple logistic regression analyses, the male gender (P < 0.01), age (P < 0.001), elevated MMP-8 (P < 0.001) and decreased MPO (P < 0.001) concentrations associated significantly with the risk for arterial disease, and provided an area under curve (AUC) of 0.97 in the Receiver operating characteristics analyses. In multiple linear regression analyses, HNE correlated with both MMP-8 (P < 0.001) and MPO (P = 0.008) concentrations. Combination of high MMP-8 and low MPO level in serum eventually reflecting selectively modified neutrophil degranulation may indicate increased risk for arterial disease.

Chlamydia pneumoniae infection is associated with elevated body mass index in young men.

Chlamydia pneumoniae infection is said to be associated with obesity. We studied the association between C. pneumoniae infection and inflammation and increased BMI in 891 Finnish military recruits. IgG seropositivity in arrival and departure serum samples during 6-12 months of military service was considered as persistence of antibodies and a possible indication of chronic infection. Persistently high C-reactive protein (CRP) level (elevated on arrival and departure) (OR 2.2, 95% CI 1.3-3.9), and persistent C. pneumoniae antibodies (OR 2.1, 95% CI 1.5-2.8) were significant risk factors for overweight (BMI 25 kg/m2). In addition, those who had persistent antibodies and persistently elevated CRP levels, or those who had either of them, had a significantly higher BMI (kg/m2) compared to those who had neither of them (25.8 vs. 24.6 vs. 23.5, respectively; P<0.001). These results provide new information about the association between possible chronic C. pneumoniae infection and obesity in young men.

Effects of CD14, TLR2, TLR4, LPB, and IL-6 gene polymorphisms on Chlamydia pneumoniae growth in human macrophages in vitro.

Chlamydia pneumoniae is an obligate intracellular gram-negative bacterium, which causes respiratory infections in humans. It can infect various cell types, e.g. vascular endothelial cells, smooth muscle cells and monocyte-derived macrophages in vitro. The susceptibility of macrophages from healthy individuals to C. pneumoniae infection is highly variable. In this study, we evaluated the effects of innate immunity genes CD14 -260 C>T, TLR2 Arg753Gln, TLR4 Asp299Gly, LBP Phe436Leu and IL6 -174 G>C polymorphisms on C. pneumoniae growth in human macrophages in vitro. The growth of C. pneumoniae was highest in CD14 -260 C>T TT genotype cells and the difference to CC and CT genotypes was statistically significant (P = 0.032 and 0.022 respectively). The G-allele of the IL6 -174 G>C polymorphism had a positive influence on chlamydial growth; the difference was statistically significant only between CC and GC genotypes (P = 0.018). TLR2 Arg 753Gln, TLR4 Asp299Gly, LBP Phe436Leu polymorphisms showed no effect on chlamydial growth.

The genus-specific antigen of Chlamydia: resemblance to the lipopolysaccharide of enteric bacteria.

A strong immunological cross-reaction between a major glycolipid antigen of Chlamydia and the innermost (Re) core of the lipopolysaccharide of enteric bacteria was demonstrated with the aid of mutants in which the Re structure is exposed. The chlamydial glycolipid resembled the Re lipopolysaccharide in molecular size, solubility, and endotoxic properties and may thus be functionally equivalent to lipopolysaccharide, an essential and characteristic component of the outer membrane of Gram-negative bacteria.

Susceptibility of human monocyte-macrophages to Chlamydia pneumoniae infection in vitro is highly variable and associated with levels of soluble CD14 and C. pneumoniae IgA and human HSP-IgG antibodies in serum.

Chlamydia pneumoniae, an intracellular microbe, causes respiratory infections and may participate in the development of atherosclerosis. It is able to survive and multiply in macrophages. The susceptibility of monocyte-macrophages from healthy individuals to C. pneumoniae infection in vitro was studied. Intracellular growth of C. pneumoniae, as an indicator of susceptibility to infection, was compared to serum levels of C-reactive protein, soluble CD14 (sCD14), human heat shock protein (HSP)-IgG, human HSP-IgA, C. pneumoniae IgG and IgA antibodies. The production of C. pneumoniae in infected macrophages was highly variable, ranging from 0 to 638 chlamydial genomes per human genome. Chlamydia pneumoniae production associated positively with serum C. pneumoniae IgA (titre: > or =10) and hHSP-IgG and negatively with sCD14 concentration. The association between sCD14 concentration, C. pneumoniae IgA and human HSP-IgG antibodies and C. pneumoniae production was statistically significant only among males. Age and gender did not correlate with the production. We hypothesize that persons whose macrophages cannot restrict the growth of C. pneumoniae are more prone to chronic infection by this agent.

Acute Chlamydia pneumoniae infections in asthmatic and non-asthmatic military conscripts during a non-epidemic period.

Chlamydia pneumoniae respiratory tract infections were studied in 512 male military conscripts (123 asthmatic and 389 non-asthmatic) taking part in 180-day service between July 2004 and July 2005 in Kajaani, Finland. Respiratory tract infections requiring a medical consultation were analysed prospectively. At baseline, at end of service, and during each episode of respiratory infection, blood samples were obtained for measurement of C. pneumoniae antibodies. Data concerning the clinical features of each infection episode were collected. Serological evidence of acute C. pneumoniae infection was found in 34 of the 512 conscripts with antibody data available, including 9.8% of the asthmatic subjects and 5.7% of the non-asthmatic subjects (p 0.111). A serological diagnosis could be made for 25 clinical episodes in 24 conscripts. The spectrum of respiratory tract infections included 13 episodes of mild upper respiratory tract infection and seven episodes of sinusitis, with five episodes involving asthma exacerbation. Two of three pneumonias were primary infections. Primary infections were diagnosed in five subjects, and re-infection/reactivation in 19 subjects, with the latter comprising 12 non-asthmatic subjects and seven asthmatic subjects (p 0.180). Prolonged infections were present in six asthmatic subjects and one non-asthmatic subject (p 0.001). A wide variety of respiratory tract infections, ranging from common cold to pneumonia, were associated with serologically confirmed C. pneumoniae infections. Infections were often mild, with common cold and sinusitis being the most common manifestations. Acute, rapidly resolved C. pneumoniae infections were equally common among asthmatic subjects and non-asthmatic subjects, whereas prolonged infections were more common among subjects with asthma.

Inhibitory effect of dietary phenolic compounds on Chlamydia pneumoniae in cell cultures.

Chlamydial infections are very common worldwide. All chlamydial species have a tendency to cause persistent infections, which have been associated to several chronic diseases including blinding trachoma, infertility and coronary heart disease (CHD). At present, no efficient treatment for the eradication of chronic chlamydial infections exists and, thus, new antichlamydial compounds are urgently needed. This study was designed to screen antichlamydial activity of natural flavonoids and other natural and structurally similar synthetic compounds against Chlamydia pneumoniae in human cell line (HL). HL cells were infected with C. pneumoniae and incubated 72 h with studied compounds. Reduction in the number of inclusions was determined with immunofluorescence staining. In vitro minimum inhibitory concentration was also determined for some of the most active compounds. Thirty seven percentage of the studied compounds (57 in total) were highly active against C. pneumoniae and all the studied compounds were non-toxic to the host cells at studied concentrations. Our study revealed direct antichlamydial effect for selected polyphenolic compounds against C. pneumoniae, in vitro. We also demonstrated the ability of some of the investigated compounds to accumulate inside cells or into cell membranes and cause inhibition, even when present only prior to infection.

Prevalence and persistence of antibodies to herpes viruses, Chlamydia pneumoniae and Helicobacter pylori in Alaskan Eskimos: the GOCADAN Study.

The prevalence and persistence of antibodies against cytomegalovirus (CMV), herpes simplex virus types 1 (HSV1) and 2 (HSV2), Helicobacter pylori and Chlamydia pneumoniae were determined in Alaskan Eskimos. The study included 610 individuals (mean age 43 +/- 15 years; 45% males) participating in the Genetics of Coronary Artery Disease in Alaska Natives (GOCADAN) study. Archived serum samples and those collected during the GOCADAN study were analysed for antibodies against the above pathogens by ELISA. The current prevalence of antibody seropositivity was 94% to CMV, 90% to HSV1, 38% to HSV2, 80% to H. pylori, and 42% to C. pneumoniae. The persistence of antibodies (in both archived and current samples) against CMV, HSV1 and H. pylori was high (83%, 84% and 67%, respectively) compared with those against HSV2 (26%) and C. pneumoniae (29%). Moreover, the seroconversion rates to these organisms were low. Most individuals acquired CMV, HSV1 and H. pylori antibodies by the age of 24 years (94%, 90% and 72%, respectively), and >50% carried HSV2 and C. pneumoniae antibodies by the age of 45 years. There were gender differences in antibody seropositivity rates. Over 70% of individuals had antibodies to at least three of the five pathogens tested. The study demonstrated the high prevalence and lifelong persistence of multiple antibodies, suggesting chronic infections among Alaskan Eskimos.

Infections, inflammation, and the risk of coronary heart disease.

BACKGROUND: The role of infections and inflammation in the pathophysiology of coronary heart disease is emerging. We studied the independent and joint effects of these 2 components on coronary risk. METHODS AND RESULTS: We measured baseline levels of C-reactive protein (CRP) and antibodies to adenovirus, enterovirus, cytomegalovirus, and herpes simplex virus as well as to Chlamydia pneumoniae (Cpn) and Helicobacter pylori in 241 subjects who suffered either myocardial infarction or coronary death during the 8.5-year trial in the Helsinki Heart Study, a coronary primary prevention trial. The 241 controls in this nested case-control study were subjects who completed the study without coronary events. Antibody levels to herpes simplex type I (HSV-1) and to Cpn were higher in cases than in controls, whereas the distributions of antibodies to other infectious agents were similar. Mean CRP was higher in cases (4.4 versus 2.0 mg/L; P<0.001), and high CRP increased the risks associated with smoking and with high antimicrobial antibody levels. The odds ratios in subjects with high antibody and high CRP levels were 25.4 (95% CI 2.9-220.3) for HSV-1 and 5.4 (95% CI 2.4-12.4) for Cpn compared with subjects with low antibody levels and low CRP. High antibody levels to either HSV-1 or to Cpn increased the risk independently of the other, and their joint effect was close to additive. CONCLUSIONS: Two chronic infections, HSV-1 and Cpn, increase the risk of coronary heart disease. The effect is emphasized in subjects with ongoing inflammation, denoted by increased CRP levels.

Detection of Chlamydia pneumoniae in human nonrheumatic stenotic aortic valves.

OBJECTIVES: We sought to study the possible presence of Chlamydia pneumoniae in aortic valve stenosis (AVS). BACKGROUND: Inflammation and immune mechanisms are considered important for the pathogenesis of nonrheumatic AVS. All chlamydial species are able to cause heart infections, and seroepidemiologic studies have indicated an association between chronic C. pneumoniae infection and coronary artery disease. Furthermore, the organism has been demonstrated in atherosclerotic lesions. METHODS: Aortic valve specimens with varying degrees of macroscopic disease were obtained from 35 subjects--17 consecutive patients undergoing aortic valve replacement for treatment of nonrheumatic AVS and 18 age-matched subjects at autopsy. The possible presence of C. pneumoniae in aortic valves was studied by immunohistochemical analysis, polymerase chain reaction or transmission electron microscopy, or a combination of these. RESULTS: Positive immunohistochemical staining with C. pneumoniae specific antibody was found in 9 (53%) of 17 patients with advanced aortic valve disease requiring surgical treatment (group A), 8 (80%) of 10 cadavers with clearly macroscopic aortic valve pathology (group B) and 1 (12%) of 8 grossly normal cadaver control subjects (group C). Statistical significance with regard to the presence of C. pneumoniae was found when combined diseased subjects (groups A and B: total 17 of 27 subjects) were compared with group C (p = 0.018). However, when group A was compared with group C, there was only marginal statistical significance (p = 0.088). Finally, there was a strong statistical significance (p = 0.015) when groups B and C were compared. Chlamydia pneumoniae DNA was also found in three stenotic valves, and in two of the three tested valve specimens chlamydia-like particles were seen by electron microscopy. CONCLUSIONS: Chlamydia pneumoniae is frequently present in nonrheumatic AVS. Similarly, the high number of C. pneumoniae infections detected in the early lesions of "degenerative" AVS suggest that this pathogen may play an etiologic role in the development of this disease. The validity of this relation requires additional study.

Chlamydia pneumoniae does not increase atherosclerosis in the aortic root of apolipoprotein E-deficient mice.

In epidemiological studies, an association between cardiovascular disease and Chlamydia pneumoniae (C pneumoniae) infection has been observed. Although C pneumoniae has been shown to be present in atherosclerotic lesions, a causal relationship between C pneumoniae infection and atherosclerosis has not been demonstrated. To study this question, we used 2 strains of apolipoprotein (apo) E-deficient mice. Eight-week-old mice on an FVB background that were maintained on either a low- or a high-fat diet were infected 3 times at 1-week intervals with C pneumoniae, and atherosclerotic lesions were measured in the aortic root at 10 weeks after the primary infection. In each of the diet groups, no difference in the extent of atherosclerosis could be observed between the C pneumoniae-infected and control animals. In further studies, 2 strains of apoE-deficient mice (FVB or C57BL/6J background) were infected 4 times at 3- to 4-week intervals, and the extent of atherosclerosis was analyzed 18 weeks later. The mice were kept on either a low- or a high-fat diet. The high-fat diet increased atherosclerosis, and a difference in atherosclerosis susceptibility between the mouse strains was observed. However, C pneumoniae infection did not influence lesion size in either mouse strain. On the other hand, C pneumoniae could not be demonstrated by polymerase chain reaction in any of the atherosclerotic lesions of the infected animals studied. A small decrease in serum cholesterol and triglyceride levels 3 days after the primary infection occurred, but after that no differences in serum lipid levels compared with those in noninfected animals were evident. In the myocardium of C pneumoniae-infected mice, no inflammatory signs could be observed. We conclude that under the experimental conditions used, C pneumoniae infection does not accelerate atherogenic changes in the aortic root of apoE-deficient mice.

Joint effects of different human papillomaviruses and Chlamydia trachomatis infections on risk of squamous cell carcinoma of the cervix uteri.

This case-control study based in Nordic serum banks evaluated the joint effects of infections with genital human papillomavirus (HPV) types, and Chlamydia trachomatis in the aetiology of cervical squamous cell carcinoma. Through a linkage with the cancer registries, 144 cases were identified and 420 controls matched to them. Exposure to past infections was defined by the presence of specific IgG antibodies. The odds ratio (OR) for the second-order interaction of HPV16, HPV6/11 and C. trachomatis was small (1.0) compared to the expected multiplicative OR, 57, and the additive OR, 11. The interactions were not materially different among HPV16 DNA-positive squamous cell carcinomas. When HPV16 was replaced with HPV18/33 in the analysis of second-order interactions with HPV6/11 and C. trachomatis, there was no evidence of interaction, the joint effect being close to the expected additive OR. Possible explanations for the observed antagonism include misclassification, selection bias or a true biological phenomenon with HPV6/11 and C. trachomatis exposures antagonizing the carcinogenic effects of HPV16.

Animal models for Chlamydia pneumoniae infection.

Animal models are used extensively in the ongoing investigation of a possible causal link between Chlamydia pneumoniae infection and conditions such as asthma and cardiovascular disease. Respiratory infections have been studied in monkeys, while mouse and rabbit models have been used to study both respiratory and cardiovascular infections. The degree of disease induced in mice depends on the strain used, the virulence of the C. pneumoniae strain used, and the dose administered. A characteristic mononuclear pneumonitis occurs, although the infection is systemic and the agent is found outside the lungs, in the circulation, spleen and liver. The infective dose used in the model tends to produce persistent infection, with inflammation continuing after the agent can no longer be cultured from the lungs. In reinfected animals the titre of infective chlamydia in lungs is much diminished, but the inflammation can be quite marked. The continuous persistence of the agent can be demonstrated by polymerase chain reaction (PCR), or, in chronically infected animals, after immunosuppression with cortisone. New Zealand White (NZW) rabbits provide an experimental model, not only for lung infections, but also for C. pneumoniae-induced atherosclerosis. Three laboratories have now reported that after inoculation, plaques develop in the arterial walls of experimental animals on a normal diet. In addition, one laboratory has reported from their studies on atherosclerosis in apoE-deficient and normal mice, that the persistence of the agent in aortic walls could be seen. Further studies are needed to evaluate the effect of the strain of chlamydia and dosage used, the importance of reinfection, the effect of diet and the effect of antibiotic treatment in these models.

Association of Helicobacter pylori infection with elevated serum lipids.

Helicobacter pylori causes a chronic gastric infection, which has been associated with coronary heart disease. To evaluate the mechanisms of this association, we studied whether the infection affects serum lipid levels as previously shown in acute infections. We analysed the serum samples of 880 males who participated in a reindeer herders' health survey in Northern Finland in 1989. H. pylori IgG and IgA antibodies were measured by enzyme-linked immunosorbent assay and triglyceride, total cholesterol and high-density lipoprotein cholesterol concentrations by routine enzymatic methods. A total of 52% of the subjects were positive for both H. pylori specific IgG and IgA and 31% were antibody-negative. The serum triglyceride and total cholesterol concentrations were significantly higher in the males with positive IgG and IgA antibody titres for H. pylori than in the males with no signs of infection (1.20 vs. 1.03 mmol/l, P < 0.001 and 6.59 vs. 6.11 mmol/l, P < 0.001, respectively). The associations remained statistically significant in non-smokers after the adjustment for age, body mass index (BMI) and social class. The finding supports the hypothesis that chronic infections may modify the serum lipid profile in a way that increases the risk of atherosclerosis.

Heat shock protein 60 autoimmunity and early lipid lesions in cholesterol-fed C57BL/6JBom mice during Chlamydia pneumoniae infection.

Chronic Chlamydia pneumoniae infection and autoimmunity to heat shock protein 60 (Hsp60) have both been documented to be associated with atherosclerosis. Herein, we studied the effects of C. pneumoniae infection and a diet with a low-cholesterol supplement on the development of autoantibodies to mouse Hsp60 and early lipid lesions in the aortic valve of C57BL/6JBom mice. In addition, pulmonary infection was investigated. C57BL/6JBom mice were given one to three C. pneumoniae inoculations and fed either a regular diet or a diet enriched with 0.2% cholesterol. Autoantibody responses against mouse Hsp60 developed in both diet groups when the mice were infected with C. pneumoniae and in uninfected mice fed a cholesterol-enriched diet. C. pneumoniae infections increased subendothelial foam cell accumulation in mice on a 0.2% cholesterol-enriched diet (p = 0.022), without apparent hypercholesterolemia. These in vivo data suggest that autoantibodies against mouse Hsp60 develop as a consequence of cholesterol feeding and repeated C. pneumoniae infections. Further, infectious burden increased early lipid lesions in C57BL/6JBom mice fed a cholesterol-enriched diet.

Effect of pravastatin in mildly hypercholesterolemic young men on serum matrix metalloproteinases.

Pravastatin decreases serum MMP-9 concentration in clinically healthy men. This may reflect reduction of nonsymptomatic chronic arterial inflammation.

Oral empiric treatment of community-acquired pneumonia. A multicenter, double-blind, randomized study comparing sparfloxacin with roxithromycin. The Scandinavian Sparfloxacin Study Group.

STUDY OBJECTIVE: Comparison of efficacy and safety of sparfloxacin (Spfx) vs roxithromycin (ROXI) for treatment of community-acquired pneumonia (CAP). DESIGN: Multicenter, double-blind, randomized study. SETTING: Twenty-three university and community hospitals in Scandinavia. PATIENTS: Three hundred four adults (> or = 18 years of age) with CAP treated as outpatients (25%) or inpatients (75%). INTERVENTIONS: Randomization 1:1 to Spfx, 400 mg on day 1, then 200 mg once daily, or ROXI, 150 mg twice daily, 10 to 14 days. Safety and efficacy analyses in intention-to-treat (ITT) and evaluable populations. RESULTS: Three hundred three of 304 patients were included in the ITT and safety analyses and 260 (86%) were evaluable at the end of follow-up. Streptococcus pneumoniae was the cause of pneumonia in 62 (20%) patients (11 with bacteremia), Chlamydia pneumoniae in 40 (13%), and Mycoplasma pneumoniae in 38 (13%) patients. The success rates for Spfx and ROXI at the end of follow-up were 82% and 72%, respectively, in the ITT population, and 94% and 79%, respectively, in the evaluable population. The odds ratio Spfx/ROXI for success was 4.5 (95% confidence interval, 1.9, 10.8) for the evaluable population. Both drugs were, overall, equally safe. GI symptoms were the most common adverse experiences in both groups. Prolongation of QTc, without clinical symptoms, was seen in 3% of Spfx patients and in 1% of ROXI patients, and photosensitivity, mostly mild to moderate, was seen in 5% of the Spfx group. CONCLUSIONS: Oral treatment with Spfx was superior to ROXI for the treatment of moderately severe CAP. Spfx was effective for all isolated pathogens, including S pneumoniae, and may be an alternative for empiric treatment of CAP, especially in areas with a high incidence of beta-lactam-resistant pneumococci.