M. J. M. Meddens

The role of bacterial adherence in the pathogenesis of infective endocarditis

SummaryBacterial adherence as a result of specific surface properties may be a contributory factor in the pathogenesis of bacterial endocarditis giving certain types of bacteria a selective advantage to cause this disease. Adherence could interact with other pathogenetic mechanisms, and this interaction could promote or hamper the development of endocarditis. Dextran production by streptococci, the activation of the clotting system by monocyte tissue thromboplastin, and phagocytic removal of bacteria from the vegetational surface by granulocytes and monocytes are examples of interacting mechanisms that could contribute to the pathogenesis of bacterial endocarditis.ZusammenfassungDie Adhärenz von Bakterien infolge spezifischer Oberflächeneigenschaften ist möglicherweise ein pathogenetischer Faktor in der Entwicklung der bakteriellen Endokarditis. Bestimmte Bakterientypen sind selektiv bevorzugt an der Entstehung dieser Erkrankung beteiligt. Es kann angenommen werden, daß Adhärenz und pathogene Mechanismen in Wechselwirkung treten, was sich auf die Entstehung der Endokarditis fördernd oder hemmend auswirken könnte. Beispiele einer solchen Interaktion, die zur Pathogenese der bakteriellen Endokarditis beitragen könnte, sind Dextranbildung durch Streptokokken, Aktivierung des Gerinnungssystems durch Gewebethromboplastin der Monozyten und die Phagozytose von Bakterien von der Oberfläche der Vegetationen durch Granulozyten und Monozyten.

Role of granulocytes in the prevention and therapy of experimental Streptococcus sanguis endocarditis in rabbits.

The contributions of granulocytes to the prevention and therapy of Streptococcus sanguis endocarditis with procaine benzylpenicillin (PBP) was investigated in rabbits. Depletion of granulocytes by treatment with mechlorethamine appeared to have no significant effect on either the prophylactic or therapeutic activities of PBP. Administration of 3,000 IU of PBP before inoculation with S. sanguis retarded the course of the endocarditis for only 24 h whether granulocytes were normal or depressed in numbers. Prophylaxis with either 15,000 or 30,000 IU of PBP was equally effective in non-granulocytopenic and granulocytopenic rabbits. Treatment of established infections with PBP at doses of 3,000 to 300,000 IU of PBP at 12-h intervals for 48 h was equally effective in rabbits with normal and depressed numbers of granulocytes. The effect of 3,000 IU of PBP was equivalent, however, to that of granulocytes alone, as shown by the fact that the numbers of CFU per gram of vegetation in the granulocytopenic rabbits treated with this dose of PBP and in the non-PBP-treated control rabbits were not significantly different.

Hamster model for herpes simplex virus infection of the central nervous system

SummaryAdult Syrian hamsters were inoculated with a mouse brain passage of herpes simplex virus type 1 (HSV-1) along an intradermal and an oral route after local scarification. For both routes, clinical symptoms of central nervous system (CNS) involvement were seen in the period between five and 12 days post infection. Compared with the route via the buccal mucosa, CNS involvement by intradermal infection is easier to establish. With a minimum dose of 2 × 104 TCID50 virus via the intradermal route, an infection rate of 80% or more can be obtained reproducibly and detected simply by clinical observation without need of a survey of the humoral immune response. Scarification of the skin prior to inoculation was found to be essential for establishment of the CNS infection.ZusammenfassungErwachsene syrische Hamster wurden auf intradermalem sowie auf oralem Infektionsweg nach lokaler Skarifizierung mit Herpes simplex-Virus Typ 1 (HSV-1) aus Mäusegehirn infiziert. Bei beiden Methoden wurden Symptome einer Beteiligung des Zentralnervensystems (ZNS) in der Periode zwischen fünf und 12 Tagen nach der Infektion beobachtet. Die ZNS-Beteiligung ist mit der intradermalen Infektion leichter auszulösen als durch Inokulation der Wangenschleimhaut. Mit einer Mindestdosis von 2 × 104 TCID50 Virus auf intradermalem Weg kann reproduzierbar eine Infektionsquote von mindestens 80% erreicht werden, was durch klinische Beobachtung leicht festzustellen ist. Deshalb ist eine serologische Überwachung der Immunreaktion für die Feststellung einer HSV-Infektion nicht erforderlich. Die Skarifizierung der Haut vor der Inokulation erwies sich als unabdingbar für die Auslösung einer intrazerebralen Infektion.

Role of granulocytes and monocytes in the prevention and therapy of experimental Staphylococcus epidermidis endocarditis in rabbits.

Rabbits with endocarditis caused by Staphylococcus epidermidis were studied to determine the parts played by granulocytes and monocytes in the prevention or outcome of therapy with cloxacillin. Both monocytes and granulocytes influenced prophylaxis with cloxacillin. The amount of cloxacillin needed to prevent infection in 50% of the rabbits was significantly less in control rabbits than in those selectively depleted of monocytes, as it was also in rabbits selectively depleted of monocytes compared with those that had both granulocytopenia and monocytopenia. Granulocytes strongly potentiated the effect of cloxacillin during prophylaxis, whereas the contribution of monocytes was merely additive. Monocytes also contributed to the effect of therapy with cloxacillin, partially via a cloxacillin-independent mechanism and partially by potentiation of the effect of cloxacillin. Granulocytes did not appear to affect cloxacillin therapy. Results of this study suggest that currently used regimens for prophylaxis and treatment of S. epidermidis endocarditis may need to be adjusted for neutropenic patients.

The role of monocytes in infective endocarditis

Traditionally, the leading role in the pathogenesis of infective endocarditis is assigned to bacterial virulence factors, whereas the contribution of host factors is deemed to be minor. According to some recent clinical reports, however, immunocompromised patients were found to constitute a significant part of the population with endocarditis (1, 2).