Interferon‐gamma and resistance to bacterial infectionsCZARNIECKI, CHRISTINE W.; SONNENFELD, GERALD
doi: 10.1111/j.1699-0463.1993.tb00073.xpmid: 8457320
Since its initial description as an antiviral, it has become clear that Interferon‐γ (IFN‐γ) has potent immunoregulatory and cell growth regulatory activities. As a result of these additional activities, it is now apparent that IFN‐γ plays a major role in regulation of bacterial infections. IFN‐γ can be both induced by bacteria and bacterial products; endogenous IFN‐γ production has been shown to play a protective role in the natural host response to several bacterial infections; and administration of exogenous IFN‐γ is effective in the prevention and treatment of bacterial infections in numerous animal model systems. Although it is now clear that IFN‐γ plays a role in regulation of bacterial infections, the mechanisms of its anti‐bacterial effects in vivo remain to be established due to the pleiotropic nature of IFN‐γ activity.
Demonstration of toxin A and B by polymerase chain reaction and McCoy cell assay in clinical isolates of Clostridium difficile from DenmarkKNUDSEN, J. D.; TVEDE, M.
doi: 10.1111/j.1699-0463.1993.tb00074.xpmid: 8457321
A polymerase chain reaction (PCR) for demonstration of gene fragments of Clostridium difficile was established. One hundred and sixty‐eight clinical isolates of C. difficile from three population groups were tested for production of cytotoxins by McCoy cell line assay (MCA) and for fragments of toxin A and B genes by PCR. The fragments for PCR amplification were at the 5′ end of the toxin genes, which was found to be specific for C. difficile. Full agreement between the PCR and MCA results was found with respect to toxicity. Fifty‐eight of the 168 strains were cytotoxin positive. Isolates from 41 normal healthy children did not differ regarding cytotoxicity compared to isolates from hospitalized children. In adult hospitalized patients a much higher frequency of toxin‐producing isolates was found. In two strains from two children, not of the same family, only the toxin A gene fragment was demonstrated, indicating that some strains of C. difficile only harbour the gene for enterotoxin. When two isolates from different periods of time were tested from 36 of the healthy children, a variation in cytotoxicity was found: in seven children strains changed from non‐toxic to toxic and in four vice versa. This may be explained by a fluctuating colonization of toxic and non‐toxic C. difficile strains, or it may indicate the need for examination of more than one strain from a positive faecal sample to demonstrate cytotoxicity.
In vitro antimicrobial susceptibility testing of rapidly growing mycobacteria using the tablet diffusion method: resistance pattern of Norwegian Mycobacterium fortuitum and Mycobacterium chelonae isolatesHOEL, TERJE; CASALS, JOSÉ B.; ENG, JAN
doi: 10.1111/j.1699-0463.1993.tb00076.xpmid: N/A
Thirty‐one Norwegian clinical isolates of rapidly growing mycobacteria classified as Runyon's group IV, including 20 Mycobacterium fortuitum and 11 Mycobacterium chelonae strains, were found resistant to a majority of tuberculostatic agents. Minimal inhibitory concentration (MIC) was determined for twelve other antimicrobial agents: amikacin, tobramycin, streptomycin, cefoxitin, imipenem, norfloxacin, ciprofloxacin, doxycycline, erythromycin, fusidic acid, co‐trimoxazole and capreomycin. The agar plate dilution method was employed and compared with the agar tablet diffusion method. Regression lines were established correlating MIC values and inhibition zones. The agar tablet diffusion method was found to be a simple and useful method for testing antimicrobial susceptibilities of M. fortuitum and M. chelonae, and a good correlation between MIC values and zone sizes with twelve antimicrobial agents was revealed. Correlation coefficients for most of these antimicrobial agents were around ‐0.90. M. chelonae was generally more resistant than M. fortuitum. Four antimicrobial agents, capreomycin, norfloxacin, ciprofloxacin and amikacin, showed differences between M. fortuitum and M. chelonae large enough to allow the zone diameter to be used diagnostically.
Susceptibility pattern of Scandinavian Francisella tularensis isolates with regard to oral and parenteral antimicrobial agentsSCHEEL, OLAF; HOEL, TERJE; SANDVIK, TORSTEIN; BERDAL, BJØRN P.
doi: 10.1111/j.1699-0463.1993.tb00077.xpmid: N/A
Some recently introduced antimicrobial agents have only been incompletely evaluated for use in Francisella tularensis infections. The present study evaluated the susceptibility pattern of Scandinavian human, rodent, and hare F. tularensis isolates with respect to a selection of traditional as well as recently introduced antimicrobial agents. All strains were resistant to the following β‐lactams: penicillin, cephalexin, cefuroxime, ceftazidime, aztreonam, imipenem, and meropenem with minimal inhibitory concentrations > 32 mg/1. Against macrolides, a mixed susceptibility/resistance pattern appeared. All strains were susceptible to gentamicin, chloramphenicol, doxycycline, and four quinolones. Since the quinolones showed the lowest MIC values, and in addition give a good intracellular penetration, we conclude that future drugs to consider against tularemia should definitely include this group of antibiotics. The outpatient mode of antibiotic treatment is especially relevant as the Scandinavian variant of F. tularensis infection is nonlethal, usually pustuloglandular, and not septicemic. Therefore, oral drugs must be sought, and the quinolone group also satisfies this requirement.
Antibody profiles to the group B streptococcal beta antigen in maternal and infant paired seraFLORES, AUREA E.; NELSON, JO ANN; WU, XIAO YAN; FERRIERI, PATRICIA
doi: 10.1111/j.1699-0463.1993.tb00079.xpmid: 8457325
Antibody profiles to the purified β antigen of the c protein of group B streptococci (GBS) were studied by ELISA and Western immunoblot (WB). The sera from 139 parturient women colonized with GBS, 35 non‐colonized parturients and their newborn infants were studied by ELISA; WB was done on 76 maternal and 26 infant sera. Enzyme‐labeled anti‐IgA (α), ‐IgG (γ), ‐IgM (μ), or ‐IgG (H&L) were used as secondary antibodies. A high prevalence of antibody to the β antigen was observed by both ELISA and WB among parturient women and their newborns. IgG (H&L) ELISA titers ≥200 were found in 84% and ≥800 in 31% of the maternal sera. A significantly higher percentage of women colonized than those non‐colonized with GBS had IgG (γ) titers ≥800. A significantly higher percentage of women colonized with c protein‐positive than c‐negative strains of GBS had IgG (H&L) titers ≥3200. Twelve of 27 women with IgM antibody to the β antigen also had IgG (γ) titers ≥800 and were, in addition, colonized with GBS. Multiple molecular forms of the antigen from 25 to 140 kDa were blotted by the maternal and infant sera. Concordance in the IgG but not in IgA or IgM antibody profiles of maternal and infant paired sera was observed in the overall blotting patterns and ELISA titers. The same titer as the mother was found in 55% of the infant sera and within one dilution in 97%. This suggests active transfer of IgG antibody to the β antigen across the placenta from mother to baby.
Induction of oxidative burst response in human neutrophils by adherent StaphylococciRIBER, ULLA; ESPERSEN, FRANK; SKINHØJ, PETER; KHARAZMI, ARSALAN
doi: 10.1111/j.1699-0463.1993.tb00081.xpmid: 8384459
The ability of staphylococci adherent to silicone surfaces to induce superoxide anion (O2−) production by polymorphonuclear leukocytes (PMNs) was investigated and compared with the same activity induced by planktonic bacteria. The responses to Staphylococcus aureus strain E 2371 and Staphylococcus epidermidis strain ATCC 14990 were compared. The staphylococci were allowed to adhere to silicone catheters for 2 h at 37°C. After opsonization of adherent bacteria in 30% human AB‐positive serum, the induction of superoxide anion production by PMNs was measured in a cytochrome C reduction assay. Both bacterial strains, when adhered to the surfaces, were able to induce superoxide anion production by PMNs to about the same extent. Comparing adherent and planktonic bacteria with these two bacterial strains, it was found that planktonic S. epidermidis induced one to three times higher superoxide anion production than the adherent bacteria, whereas planktonic S. aureus induced four to seven times higher superoxide anion production than the adherent bacteria. Interstrain variation between the response to adherent and planktonic staphylococci was found. The lower phagocytic response to adherent staphylococci as compared to the response to planktonic organisms may interfere with the killing process and thereby contribute to poor clearance of these bacteria when adherent to foreign bodies such as catheters.
Survival and ultrastructural changes of Helicobacter pylori after phagocytosis by human polymorphonuclear leukocytes and monocytesANDERSEN, LEIF PERCIVAL; BLOM, JENS; NIELSEN, HENRIK
doi: 10.1111/j.1699-0463.1993.tb00082.xpmid: N/A
Few studies have been carried out on the phagocytosis and killing of Helicobacter pylori by both polymorphonuclear leukocytes (PMNs) and monocytes. In this study, H. pylori was incubated for up to 60 min either alone or with phagocytes in the presence or absence of human serum. Both non‐immune serum and immune serum were used. Reduction in the number of H. pylori, which corresponds to the killing of H. pylori, was analysed by a colony count and ultrastructural changes were studied by electron microscopy. No reduction in the number of H. pylori was found when the bacteria were incubated alone or with phagocytes in the absence of serum. It is remarkable that unopsonized H. pylori was phagocytosed. When immune serum was added to the suspensions of bacteria and phagocytes, the killing rate of H. pylori was found to depend on the ratio of H. pylori to phagocytes. Thus an excess of monocytes reduced the number of H. pylori, whereas an excess of PMNs resulted in complete killing of H. pylori. On incubation with PMNs and serum, ultrastructural changes were observed in the majority of the bacteria whether they were phagocytosed or not. Controls without serum did not show any changes in the morphology of H. pylori, indicating that components in the serum play an important role in the phagocytosis and killing of H. pylori. In contrast, several of the phagocytosed bacteria were found to be unaffected after incubation with monocytes and serum. Such preparations often contained large aggregates of platelets surrounding unaffected H. pylori. In the gastric mucosa, H. pylori is often found in excess as compared to the phagocytes. If these results can be compared to the situation in vivo, the phagocytes seem to be ineffective in the killing of H. pylori, and other immune mechanisms may therefore be of importance for the elimination of H. pylori from the gastric epithelium. The possible intracellular survival of H. pylori should be taken into account when treatment regimes for H. pylori infections are chosen.