Clindamycin Protects Nonhuman Primates Against Inhalational Anthrax But Does Not Enhance Reduction of Circulating Toxin Levels When Combined With Ciprofloxacin.

BACKGROUND: Inhalational anthrax is rare and clinical experience limited. Expert guidelines recommend treatment with combination antibiotics including protein synthesis-inhibitors to decrease toxin production and increase survival, although evidence is lacking. METHODS: Rhesus macaques exposed to an aerosol of Bacillus anthracis spores were treated with ciprofloxacin, clindamycin, or ciprofloxacin + clindamycin after becoming bacteremic. Circulating anthrax lethal factor and protective antigen were quantitated pretreatment and 1.5 and 12 hours after beginning antibiotics. RESULTS: In the clindamycin group, 8 of 11 (73%) survived demonstrating its efficacy for the first time in inhalational anthrax, compared to 9 of 9 (100%) with ciprofloxacin, and 8 of 11 (73%) with ciprofloxacin + clindamycin. These differences were not statistically significant. There were no significant differences between groups in lethal factor or protective antigen levels from pretreatment to 12 hours after starting antibiotics. Animals that died after clindamycin had a greater incidence of meningitis compared to those given ciprofloxacin or ciprofloxacin + clindamycin, but numbers of animals were very low and no definitive conclusion could be reached. CONCLUSION: Treatment of inhalational anthrax with clindamycin was as effective as ciprofloxacin in the nonhuman primate. Addition of clindamycin to ciprofloxacin did not enhance reduction of circulating toxin levels.

Factors modulating the outcome of treatment for the eradication of Helicobacter pylori infection.

A group of 180 H. pylori culture positive dyspeptic patients (64 patients with peptic ulcer, PU) completed a 2-week treatment with omeprazole, amoxicillin and metronidazole and underwent endoscopy again 6-8 weeks after the end of therapy. One hundred and twenty-four patients (68.8%) were successfully treated. Factors increasing the rates of eradication were the presence of PU (p=0.007) and anti-CagA serum antibodies (p=0.003). Factors negatively modulating eradication were the presence of coccoid forms (p=0.0008) and metronidazole-resistant strains (p=0.001); degrees of histological gastritis had no significant effect on eradication rates. Microscopic examination of smeared biopsies for the detection of the coccoid morphoytpe of H. pylori may help avoiding therapeutic failures.

Successful treatment of asymptomatic or clinically terminal bovine Mycobacterium avium subspecies paratuberculosis infection (Johne's disease) with the bacterium Dietzia used as a probiotic alone or in combination with dexamethasone: Adaption to chronic human diarrheal diseases.

A naturally occurring gastrointestinal disease, primarily of ruminants (Johne disease), is a chronic debilitating disease that is caused by Mycobacterium avium subspecies paratuberculosis (MAP). MAP infection occurs primarily in utero and in newborns. Outside our Dietzia probiotic treatment, there are no preventive/curative therapies for bovine paratuberculosis. Interestingly, MAP is at the center of controversy as to its role in (cause of) Crohn disease (CD) and more recently, its role in diabetes, ulcerative colitis, and irritable bowel syndrome (IBS); the latter two, like CD, are considered to be a result of chronic intestinal inflammation. Treatments, both conventional and biologic agents, which induce and maintain remission are directed at curtailing processes that are an intricate part of inflammation. Most possess side effects of varying severity, lose therapeutic value, and more importantly, none routinely result in prevention and/or cures. Based on (a) similarities of Johne disease and Crohn disease, (b) a report that Dietzia inhibited growth of MAP under specific culture conditions, and (c) findings that Dietzia when used as a probiotic, (i) was therapeutic for adult bovine paratuberculosis, and (ii) prevented development of disease in MAP-infected calves, the goal of the present investigations was to design protocols that have applicability for IBD patients. Dietzia was found safe for cattle of all ages and for normal and immunodeficient mice. The results strongly warrant clinical evaluation as a probiotic, in combination with/without dexamethasone.

Haemophilus influenzae type-b and non-b-type invasive diseases in urban children (<5years) of Bangladesh: implications for therapy and vaccination.

OBJECTIVE: To prospectively study the epidemiology and antibiotic resistance of Haemophilus infuenzae isolates from invasive infections in children. METHODS: Children (<5years) with pneumonia, meningitis and septicemia from three hospitals in Dhaka, Bangladesh were enrolled (1999-2003); clinical and laboratory data, and blood for cultures were collected. Cerebrospinal fluid (CSF) of meningitis cases was analyzed (Gram stain, culture and biochemical tests). Hib antigen was detected by latex agglutination (LA) in culture-negative pyogenic CSF and PCR was done for bexA gene in culture- and LA-negative pyogenic CSF. Antibiotic susceptibility was determined by E-Tests and beta-lactamase by nitrocefin stick. RESULTS: Seventy-three cases of H. influenzae infections (46 of 293 meningitis cases, 25 of 1493 pneumonia cases, 2 of 48 septicemia cases) were detected; 63%, 34% and 3% of them had meningitis, pneumonia and septicemia respectively. H. influenzae type b (Hib) caused infections in 80.8% of cases (60.3% meningitis, 20.5% pneumonia). Most (86%) infections clustered in 4-12month infants. The case-fatality in pneumonia was 8% compared to 19% in meningitis. H. influenzae isolates from pneumonia and meningitis children were equally resistant to antibiotics (46% vs 43%). Of 10 drugs tested, isolates were resistant to ampicillin (31%), chloramphenicol (42%), trimethoprim-sulfamethoxazole (44%) and azithromycin (1.4%). Multidrug-resistant (MDR) strains were equally prevalent in Hib (31%) and non-b-type (29%) isolates, and in pneumonia (31%) and meningitis (34%) cases. None was resistant to amoxicillin-clavulanate, ceftriaxone, ciprofloxacin, levofloxacin, moxifloxacin, and gatifloxacin. Of all H. influenzae infections, 40%, 4.4% and 100% of pneumonia, meningitis and septicemia cases were caused by other serotypes or non-typeable strains. All ampicillin-resistant-strains produced beta-lactamase without detection of beta-lactamase-negative-ampicillin-resistant (BLNAR) strains. CONCLUSION: Hib is a leading cause of invasive bacterial infections in infants. Multidrug-resistant H. influenzae is common and requires amoxicillin-clavulanate, ceftriaxone or azithromycin as empirical therapy with specific recommendation for use of ceftriaxone for treatment of meningitis particularly MDR cases. New fluoroquinolines has potential utility. An effective national Hib vaccination programme is essential in Bangladesh although non-Hib infections will remain an issue.

Recombinant or peptide antigens in the serology of Lyme arthritis in children.

The performance of ELISAs with the recombinant antigens decorin-binding protein A (DbpA), DbpB, and BBK32 (from Borrelia afzelii, B. garinii, and B. burgdorferi sensu stricto) and VlsE peptide antigen invariable region 6 (IR(6)) were evaluated in the serodiagnosis and follow-up of children with Lyme arthritis (LA). Serum samples were obtained from 52 children with clinically typical and serologically confirmed LA. In IgG ELISAs, at diagnosis, 50 samples were positive for BBK32, 51 for DbpA, 40 for DbpB, and 51 for IR(6). In the posttreatment follow-up, the rate of decline of the antibodies to the recombinant protein antigens or to IR(6) did not appear useful in the prediction of the treatment response or the clinical course of LA. Yet, IR(6) seems to have the greatest potential to be used universally in the diagnostic serology of Lyme borreliosis (LB). Alternate to that, the use of several specific borrelial antigens, in parallel, might improve the accuracy of serology for LB.

The effect of 5-year vitamin C supplementation on serum pepsinogen level and Helicobacter pylori infection.

We conducted a population-based, double-blind, randomized controlled trial to examine the effect of vitamin C supplementation on serum pepsinogen (PG) level, Helicobacter pylori (H. pylori ) infection, and cytotoxin-associated gene A (Cag A) status. Subjects aged 40 to 69 years living in one village in Akita prefecture, a high-risk area for gastric cancer in Japan, were recruited through annual health check-up programs. Among 635 subjects diagnosed as having chronic gastritis on the basis of serum PG levels, after excluding ineligible cases, 439 subjects were assigned to one of four groups using a 2 x 2 factorial design (0 or 15 mg/day beta-carotene and 50 or 500 mg/day vitamin C). However, based on the results from two beta-carotene trials in the United States, we discontinued beta-carotene (vitamin C supplementation was continued). Finally, 120 subjects in the low-dose group (vitamin C 50 mg), and 124 subjects in the high-dose group (vitamin C 500 mg) completed the 5-year supplementation. The difference in the change of PGI/II ratio between baseline and after 5-year follow up was statistically significant between the intervention groups among those who completed the supplementation: - 0.25 for the low-dose group and - 0.13 for the high-dose group (P = 0.046). To conclude, vitamin C supplementation may protect against progression of gastric mucosal atrophy.

Precipitin response of potato processing workers to work-related microbial allergens.

Serum samples from 61 potato processing workers and 30 urban dwellers not exposed to organic dusts (as a reference group) were examined in agar-gel precipitation test performed by Ouchterlony double diffusion method with the antigens of 12 microorganisms associated with organic dusts. Each serum was tested twice: not concentrated, and three-fold concentrated, for the detection of low levels of precipitins. The antibody response of workers to the antigen of coryneform bacterium Agromyces ramosus was high, at both not concentrated and 3-fold concentrated sera (respectively 29.5% and 45.9%)--significantly greater than in reference group (p < 0.001). Workers' response to the antigens of Gram-negative bacterium Alcaligenes faecalis and thermophilic actinomycete Thermoactinomyces vulgaris was lower (respectively 13.1% and 13.1% at not concentrated sera, 24.6% and 29.5% at 3-fold concentrated sera) but in all cases significantly greater than in reference group (p < 0.05 at not concentrated sera, p < 0.01 and p < 0.001 at 3-fold concentrated sera). The frequency of positive precipitin reactions of potato workers to antigen of Penicillium citrinum was high only at 3-fold concentrated sera (55.7%)--significantly higher compared to reference group (p < 0.001). The antibody response of potato workers to other antigens was either unspecific or low, showing no significant difference compared to reference group. Twenty eight out of 61 examined potato processing workers (45.9%) reported the occurrence of the work-related pulmonary symptoms. The frequency of positive precipitin reactions to Agromyces ramosus, Alcaligenes faecalis, Thermoactinomyces vulgaris, Penicillium citrinum and Acinetobacter calcoaceticus was significantly greater in the subgroup of 28 workers reporting work-related pulmonary symptoms compared to 33 asymptomatic workers (p < 0.05). Study results suggest that antigens of Agromyces ramosus, Alcaligenes faecalis, Thermoactinomyces vulgaris and Penicillium citrinum should be considered as potential occupational allergens, probably stimulating an adverse immunopathological reaction in the exposed potato processing workers.

New developments in diagnostic and treatment of mycoplasma infections in humans.

Several methods can be used for the diagnosis of mycoplasmal human infections. Culture is not satisfactory for fastidious species, while serological procedures allow only a retrospective diagnosis. Recently, rapid methods have become available. Antigenic detection proposed for Mycoplasma pneumoniae lacks sensitivity. Hybridization based techniques include DNA probes and mainly DNA amplification. The main usefulness of the polymerase chain reaction (PCR) is the detection of fastidious organisms such as M. pneumoniae, M. genitalium, M. fermentans, M. penetrans, but PCR can also be used for characterization of the strains for epidemiological purposes, or for detection of antimicrobial resistance genes. The major advantage of PCR for detection is its very high sensitivity. However, until now, the major drawback of this technique has been the lack of commercial kits. When available, they should provide better standardization of the technique and, if available at a reasonable cost, become the major technique for the diagnosis of mycoplasma infections. The antibiotics used for the treatment of mycoplasmal infections belong to tetracyclines, macrolides-lincosamides and fluoroquinolones. These products are highly active in vitro against mycoplasmas. However, some of them have a differential activity according to the species, and acquired resistance has been reported, mainly in genital mycoplasmas. Most of mycoplasmal infections are cured by adapted antibiotics, but they may be difficult to cure in immunosuppressed patients.