CSF oligoclonal bands in MS include antibodies against Chlamydophila antigens.

BACKGROUND: Considerable evidence suggests the role of an infectious agent in MS. The presence of Chlamydophila pneumoniae in CSF from patients with MS was shown earlier; to further examine this association the reactivity of the oligoclonal antibody response in the CSF of patients with MS to C pneumoniae antigens was determined and compared with other antigens. METHODS: Seventeen patients with MS and 14 control subjects with other neurologic disease were studied. Affinity-driven immunoblot studies and solid-phase adsorption of CSF oligoclonal bands by elementary body antigens of C pneumoniae, viral antigens (measles and herpes simplex virus-1), bacterial antigen (Escherichia coli and Staphylococcus aureus), and heat shock protein-60 were performed. RESULTS: Affinity-driven immunoblot studies demonstrated reactivity of oligoclonal bands in CSF samples from 16 patients with MS against elementary body antigens of C pneumoniae. None of the control subjects showed a prominent reactivity to elementary body antigens of C pneumoniae. In 14 of 17 patients with MS examined, oligoclonal bands were adsorbed either partially or completely from the CSF by elementary body antigens of C pneumoniae, but not by myelin basic protein, heat shock protein-60, or bacterial or viral antigens. In three patients with subacute sclerosing panencephalitis, adsorption of oligoclonal bands was seen with measles virus antigens but not with elementary body antigens of C pneumoniae. CONCLUSIONS: Oligoclonal bands in CSF of patients with MS include antibodies against Chlamydophila antigens.

Regulation by IFN-beta of inducible nitric oxide synthase and interleukin-12/p40 in murine macrophages cultured in the presence of Chlamydia pneumoniae antigens.

Chlamydia pneumoniae has been demonstrated in the cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS). Interferon-beta (IFN-beta) has favorable effects on the clinical course of MS. We investigated whether the beneficial effects of IFN-beta in MS may involve its role in regulating nitric oxide (NO) and interleukin-12 (IL-12) in macrophages, as these immune modulators form part of the innate immune response to intracellular pathogens, such as C. pneumoniae. Murine macrophages in cultures exposed to elementary body antigens or recombinant major outer membrane protein (rMOMP) of C. pneumoniae demonstrate a significant increase in NO as well as production of IL-12/p40 in culture supernatants compared with basal levels. Addition of murine IFN-beta increased NO activity in murine macrophages cultured with chlamydial antigens. Addition of neutralizing anti-IFN-beta antibody prevented the NO increase. In contrast to its effect on inducible NO synthase (iNOS), IFN-beta reduced induction of IL-12/p40 following culture with either elementary body antigens or rMOMP. Inhibition was reversed with anti-IFN-beta antibody. If C. pneumoniae infection is responsible for the inflammatory response in the pathogenesis of MS, the beneficial effects of IFN-beta in MS may be due to its enhancing intracellular NO activity while inhibiting secretion of the proinflammatory cytokine, IL-12.

Chlamydia pneumoniae and chronic skin wounds: a focused review.

The genus, Chlamydophilia, as obligate intracellular pathogens, induce chronic scarring in humans. Chlamydia pneumoniae, a common cause of pneumonia, infects endothelial cells and circulating macrophages. Evidence that C. pneumoniae is an opportunistic pathogen in chronic skin ulcers and other inflammatory skin conditions analogous to its role in atherosclerosis is reviewed.

Pyoderma gangrenosum and Chlamydia pneumoniae infection in a diabetic man: pathogenic role or coincidence?

Chlamydia Pneumoniae is not a known cause of skin infections, but unusual pathogens cause chronic infections in diabetic patients. Multiple idiopathic pyoderma gangrenosum-like (PG-like) lesions were refractory to multiple therapeutic agents in a diabetic patient who had C pneumoniae identified by serologic tests and polymerase chain reaction. Based on complete resolution by prolonged anti-chlamydial antibiotic therapy and concomitant decrease in serologic and titers determined by polymerase chain reactions, the PG-like lesions were presumed to be due to C pneumoniae.

Mechanisms of bacterial resistance to antimicrobial agents.

The 20th century has been considered the antimicrobial era--whereas the 21st century may well represent the post-antimicrobial era. The reason for this dramatic change, should it come to pass, is the development of bacterial resistance to antimicrobial agents. This emerging resistance is now challenging the clinical utility of many antimicrobial agents such that the chemotherapy of hospitalized patients with serious infections has been compromised. If the problem with resistance is to be successfully dealt with by clinicians, the mechanisms of such resistance must be known and understood. This paper thus reviews the most important mechanisms of resistance as well as some of the most important pathogens having these mechanisms. An understanding of these important microbial resistance mechanisms will help the clinician identify circumstances in which resistance may be a problem as well as evaluating the potential usefulness of an alternate antimicrobial agent against resistant microbes.

Chlamydia pneumoniae infection of the central nervous system in multiple sclerosis.

Our identification of Chlamydia pneumoniae in the cerebrospinal fluid (CSF) of a patient with multiple sclerosis (MS) led us to examine the incidence of this organism in the CSF from 17 patients with relapsing-remitting MS, 20 patients with progressive MS, and 27 patients with other neurological diseases (OND). CSF samples were examined for C pneumoniae by culture, polymerase chain reaction assays, and CSF immunoglobulin (Ig) reactivity with C pneumoniae elementary body antigens. C pneumoniae was isolated from CSF in 64% of MS patients versus 11% of OND controls. Polymerase chain reaction assays demonstrated the presence of C pneumoniae MOMP gene in the CSF of 97% of MS patients versus 18% of OND controls. Finally, 86% of MS patients had increased CSF antibodies to C pneumoniae elementary body antigens as shown by enzyme-linked immunosorbent assay absorbance values that were 3 SD greater than those seen in OND controls. The specificity of this antibody response was confirmed by western blot assays of the CSF, using elementary body antigens. Moreover, CSF isoelectric focusing followed by western blot assays revealed cationic antibodies against C pneumoniae. Infection of the central nervous system with C pneumoniae is a frequent occurrence in MS patients. Although the organism could represent the pathogenetic agent of MS, it may simply represent a secondary infection of damaged central nervous system tissue. A therapeutic trial directed at eliminating C pneumoniae from the central nervous system may provide additional information on its role in MS.

Bismuth-mediated disruption of the glycocalyx-cell wall of Helicobacter pylori: ultrastructural evidence for a mechanism of action for bismuth salts.

The mechanism of bismuth's bactericidal activity against Helicobacter pylori was investigated using transmission electron microscopy (TEM) and analytical electron microscopy (AEM); time-kill kinetic methods evaluated the effect of excess divalent cations. TEM analysis of untreated H. pylori revealed a normal morphology. In contrast, H. pylori exposed to bismuth salts had swollen, distorted cells with membrane-cell wall blebbing and a cytoplasm containing electron-dense, sometimes crystalline aggregates. By AEM, swollen cells contained bismuth at the cell periphery, whereas bacillary forms contained cytoplasmic bismuth localizations. Time-kill studies showed that the bactericidal activity of bismuth could be prevented by pretreatment with divalent cations. The effects of bismuth salts on the glycocalyces-cell walls of H. pylori with reversal of bactericidal activity by divalent cations are identical to those produced by other polycationic agents on various gram-negative bacilli. We conclude that disruption of the glycocalyces-cell walls of H. pylori is one mechanism of action for bismuth salts.

In-vitro evaluation of nitrofurantoin as an alternative agent for metronidazole in combination antimicrobial therapy against Helicobacter pylori.

Increasing metronidazole resistance suggests the need for alternative antibiotics for combination therapy of Helicobacter pylori infections. We evaluated a metronidazole-resistant and a clarithromycin-resistant strain of H. pylori under stationary growth phase conditions that favoured physiological conditions in order to determine if nitrofurantoin might be a suitable alternative for metronidazole in combination therapy. The results demonstrated that the triple combination of bismuth, tetracycline and nitrofurantoin achieved greater bactericidal activity against these two strains than did the combination of bismuth, tetracycline and metronidazole. These results suggest that further evaluation is warranted.

The bactericidal activity of clarithromycin versus ampicillin alone and in combination with omeprazole and/or bismuth against clarithromycin-susceptible and clarithromycin-resistant strains of Helicobacter pylori.

We evaluated the in vitro bactericidal effect of clarithromycin versus ampicillin alone and in combination against clarithromycin-sensitive and clarithromycin-resistant strains of Helicobacter pylori. No combination containing clarithromycin achieved complete bactericidal effect against clarithromycin-resistant strains. Complete bactericidal effect was achieved for all strains by triple-agent combinations that contained bismuth, omeprazole, and relatively high concentrations of ampicillin. These in vitro results demonstrate the additive bactericidal activity provided by a combination of agents for the eradication of H. pylori. Bismuth may play a particularly important role in the bactericidal effect.

Laboratory tests in critical care.

A simple clinical index can be utilized to identify occult bacterial infections in the critical care unit. Use of this index enables the critical care physician to estimate the likelihood of occult infection, thus reducing and directing the diagnostic effort. This article reviews nonspecific screening tests used in the index.

Association of borderline oxacillin-susceptible strains of Staphylococcus aureus with surgical wound infections.

Staphylococcus aureus isolates which produce type A staphylococcal beta-lactamase have been associated with wound infections complicating the use of cefazolin prophylaxis in surgery. To further evaluate this finding, 215 wound isolates from 14 cities in the United States were characterized by antimicrobial susceptibility and beta-lactamase type and correlated with the preoperative prophylactic regimen. Borderline-susceptible S. aureus isolates of phage group 5 (BSSA-5), which produce large amounts of type A beta-lactamase and exhibit borderline susceptibility to oxacillin, comprised a greater percentage of the 120 wound isolates associated with cefazolin prophylaxis than they did of the 95 isolates associated with other prophylactic regimens (25% versus 12.6%, respectively; P < 0.05). In contrast, methicillin-resistant S. aureus isolates were distributed evenly between the two groups (8.3% versus 11.6%, respectively). In vitro assays demonstrated that cefazolin was hydrolyzed faster by BSSA-5 strains than by other beta-lactamase-producing, methicillin-susceptible strains (1.54 versus 0.50 microg/min/10(8) CFU, respectively; P < 0.0001). These data demonstrate that BSSA-5 strains are a distinct subpopulation of methicillin-susceptible S. aureus which frequently cause deep surgical wound infections. Cefazolin use in prophylaxis is a risk factor for BSSA-5 infection.

Avoiding fluoroquinolone resistance. Strategies for primary care practice.

The therapeutic usefulness of fluroquinolones for serious and difficult-to-treat infections is well documented. However, with increasing reports of organisms becoming resistant to the agents (most often the pseudomonads, staphylococci, and streptococci), the usefulness of this class of antibiotics is being threatened. Appropriate and judicious prescribing of this class of antimicrobials can greatly aid in preserving the therapeutic value of fluoroquinolones for the treatment of infections in the future.

High-level aminoglycoside-resistant enterococcus causing endocarditis successfully treated with a combination of ampicillin, imipenem and vancomycin.

We describe a case of bacterial endocarditis caused by Enterococcus faecalis, which was highly resistant to aminoglycosides. The patient was successfully treated with a combination of ampicillin, imipenem and vancomycin. We believe this to be the first case in the literature to be treated successfully with this combination.

Lactobacillus bacteremia: description of the clinical course in adult patients without endocarditis.

Lactobacillus bacteremia in the absence of endocarditis is a rare entity, and the clinical relevance of such bacteremia remains unclear. The clinical courses of lactobacillus bacteremia without endocarditis in 43 previously described patients and 12 new patients were reviewed. Bacteremia with Lactobacillus alone occurred in 34 (62%) of the patients, and 12 (22%) of the patients had bacteremia with other organisms, including Lactobacillus. Lactobacillus was isolated from another site in 18 (33%) of these patients. Intravenous catheter infections were not noted in these patients. Underlying conditions included cancer (6 patients), organ transplantation (9), diabetes mellitus (4), and recent surgery (12). Fever occurred in all patients, and eight (15%) of the patients experienced a sepsis syndrome. The mortality rate was 14%; however, only three deaths were attributed soley to lactobacillus sepsis. Lactobacillus bacteremia is an uncommon condition that usually occurs in patients with severe underlying illnesses and is frequently seen as a part of a polymicrobial infection. Blood cultures positive for Lactobacillus represent true infection and not contamination. Although resistance to commonly used antibiotics is common, the mortality rate associated with this bacteremia appears to be low.