[Invasive infections due to group A beta-haemolytic streptococci in two families]. / Invasieve infecties door beta-hemolytische streptokokken uit groep A binnen twee families.

An invasive beta-haemolytic Lancefield group A streptococcal (GAS) infection was diagnosed in 4 patients: a 70-year-old woman, her 71-year-old husband, a 62-year-old woman and her 43-year-old son. In the married couple the infection was caused by GAS-type TB3264M100. The woman had a pneumonia, whilst her husband developed a streptococcal toxic shock-like syndrome; he died. The other woman and her son were infected with GAS-type T6M6. The son died of a circulatory arrest due to necrotizing fascitis from a wound in his arm. His mother recovered following a severe tonsillitis. The number of invasive GAS infections has increased in the past decades. GAS infections occur mostly in isolated cases, but clusters of patients are also seen, like the two described here. The risk of an invasive GAS-infection is greatest if one has been in the neighbourhood of the index patient during the week prior to the diagnosis in that patient. According to the latest (American) guidelines, there is no reason for prophylactic treatment of the close contacts of patients.

Efficacy and safety of azithromycin versus benzylpenicillin or erythromycin in community-acquired pneumonia.

Azithromycin, a recently introduced antibiotic, offers the potential advantages of short-course administration and lower toxicity compared to other macrolides. Approved for the treatment of mild pneumonia, this drug was investigated in a study of patients hospitalized for community-acquired pneumonia. In an open-labelled randomized study, oral azithromycin was compared with intravenous benzylpenicillin in patients suspected to have pneumococcal pneumonia. Azithromycin was also compared with erythromycin, both administered orally, in all other patients. Three hundred thirty-four patients with community-acquired pneumonia were hospitalized, 108 of whom were randomized; 104 could be evaluated. A need for intravenous therapy was the most common reason for exclusion. In the pneumococcal group, 35 patients received azithromycin and 29 benzylpenicillin. The clinical and radiological success rate achieved with azithromycin (83%) was considerably higher than that achieved with benzylpenicillin (66%), though the difference was not significant. In the non-pneumococcal group, 19 patients received azithromycin and 21 erythromycin; no differences in the success rate were found (79% and 76%, respectively). Eight patients on azithromycin had a blood culture positive for Streptococcus pneumoniae; in three of these patients therapy was changed. None of the five patients with pneumococcal bacteraemia who received benzylpenicillin required a change in therapy. It is concluded that oral azithromycin, administered as short-course therapy, is an appropriate antibiotic for treating patients with community-acquired pneumonia. However, it is not yet certain that azithromycin is a good choice for patients with pneumococcal bacteraemia.

Nosocomial catheter-associated bacteriuria: a clinical trial comparing two closed urinary drainage systems.

We compared the time of onset and incidence of nosocomial bacteriuria between two different closed urinary drainage systems: a simple closed drainage system containing an antireflux valve ('Urias A-4') and a complex closed drainage system ('Curity Infection Control System') incorporating: (1) a preconnected, coated catheter, (2) a tamper discouraging seal at the catheter-drainage tubing junction, (3) a drip chamber, (4) an antireflux valve, (5) a hydrophobic drainage bag vent and (6) a povidone-iodine releasing cartridge in line with the outlet tube of the urine collection bag. 181 non-bacteriuric patients, requiring catheter drainage for more than 48 h, were assigned by chance to either of the two systems. Bacteriological monitoring of bladder urines of the enrolled patients was performed every 24 h by establishing viable counts and identification of all microorganisms. No differences in the onset and incidence of nosocomial bacteriuria between the two urine drainage system groups were noted. We conclude that additional complex features aimed at preventing intraluminal spread of bacteria did not reduce the risk of urinary tract infection, compared to a simple closed urinary drainage system.

A comparison of four film-type dressings by their anti-microbial effect on the flora of the skin.

Two polyurethane dressings ('Tegaderm' and 'OpSite') were compared with their respective povidone iodine and chlorhexidine acetate-impregnated dressings ('Tegaderm Plus' and 'OpSite CH') for their effectiveness in reducing recolonization of skin after application of the dressings. After 7 days the average number of cfu on undamaged skin, covered with the four dressings, was significantly lower than the number of cfu on skin which had not been covered. The number of cfu on the skin covered with OpSite CH was significantly lower than with all other dressings tested. OpSite CH possesses most anti-microbial activity in relation to the flora of the skin.

A quantitative evaluation of pulmonary macrophage kinetics.

A new mathematical approach to the calculation of the kinetics of macrophages in a tissue compartment is presented. This approach, which takes into account the influx of monocytes into the compartment, the local division of mononuclear phagocytes, and the efflux of macrophages from the compartment, was applied to data on the pulmonary macrophages of mice in the normal steady state. The results show that at least 70% of the pulmonary macrophage population is supplied by monocyte influx and at most 30% by local division of immature mononuclear phagocytes originating from the bone marrow. The calculated turnover time of pulmonary macrophages is about 6 days, and the turnover amounts to 14.6 X 10(3) macrophages/hr.

Characteristics of human monocytes cultured in the Teflon culture bag.

Blood monocytes from healthy volunteers were isolated by Ficoll-Isopaque centrifugation and cultured (together with lymphocytes) in medium 199 with 20% heat-inactivated newborn calf serum in a Teflon culture bag. Quantifiable data on survival showed that up to 21 days of culture, approximately 40% of the initial number of monocytes were still viable. Such cultures could be maintained for more than 8 weeks without refeeding. The monocytes exhibited the morphology of macrophages after 5-7 days of culture, and increased in size during culture. Less than 1% of the cells became giant cells even after long culture periods. Almost all cultured monocytes were positive for alpha-naphthyl butyrate esterase, whereas the peroxidase-positive granules disappeared during the first week of culture. After long culture times increasing amounts of lysozyme and angiotensin-converting enzyme were detected in the culture supernatants. Phagocytosis of staphylococci did not decrease appreciably during culture, and the same holds for intracellular killing of these bacteria. Chemotactic activity decreased during culture, whereas the chemokinetic response of the monocytes persisted.

The current view on the origin of pulmonary macrophages.

In the present contribution the current view on the origin of macrophages is briefly summarized. Recent studies on the kinetics of pulmonary macrophages in the normal steady state and during an inflammatory reaction induced by heat-killed BCG applied intravenously or by aerosol are reported in more detail, and the effect of glucocorticosteroids on the kinetics of these cells is described. The results support the general conclusion that pulmonary macrophages derive mainly from circulating monocytes, exclude the existence of an interstitial pool of dividing precursors cells, and provide evidence that the limited local production of pulmonary macrophages is the result of division of mononuclear phagocytes recently derived from the circulation.

Functions of peripheral-blood monocytes and granulocytes in cutaneous T-cell lymphoma.

Granulocyte and monocyte functions (phagocytosis, intracellular killing, chemokinesis and chemotaxis) and the opsonic and chemotactic activity of the serum of twenty-two patients with cutaneous T-cell lymphoma were assessed. Granulocyte functions were within the normal control range in most cases. The monocyte functions showed more variation in the test results; in six out of twenty-two patients intracellular killing of Staphylococcus aureus was depressed and in four out of ten patients a disturbance in monocyte chemotaxis was found. Two patients with a decreased chemotactic response also had an impaired capacity to kill S. aureus. No correlation was found between the cell disturbance and susceptibility to infection, stage of the disease, or clinical course in these patients.

The origin of pulmonary macrophages.

The controversy as to whether pulmonary macrophages derive from monocytes or from precursor cells in the pulmonary interstitium has been solved by quantitative analysis of 3H-thymidine labeling data on the circulating monocytes and the total population of pulmonary macrophages isolated from mice by lavage and enzyme digestion of lung tissue. It was found that in the normal steady state, during acute inflammatory reactions, and under long-term corticosteroid treatment, pulmonary macrophages derive mainly from circulating monocytes which enter the lungs and become pulmonary macrophages within a few hours. Local division of pulmonary macrophages made only a minor contribution to the maintenance of the population; a dividing precursor cell population located in the interstitium of the lung could not be demonstrated. The few mononuclear phagocytes dividing locally in the lung have most probably arrived recently from the circulation and originate in the bone marrow. These dividing cells already have the characteristics of pulmonary macrophages.

Comparison of the in vivo and in vitro proliferation of monoblasts, promonocytes, and the macrophage cell line J774.

Mononuclear phagocytes are localized in the bone marrow compartment (monoblasts, promonocytes and macrophages), the circulation (monocytes), and the tissues and serous cavities (macrophages). In vivo and in vitro studies done in murine bone marrow have shown that monoblasts and promonocytes are the most immature, dividing cells of the mononuclear phagocyte cell line; monocytes and resident macrophages do not divide. A very small percentage of the mononuclear phagocytes in the tissues, which are bone-marrow derived and have already the morphology of macrophages, divide once in vivo. The progeny of these dividing cells contribute to the maintenance of the tissue population of macrophages under steady-state conditions. In vitro an appreciable percentage of (young) macrophages divide, in all probability due to the influence of colony-stimulating factor. The cells of macrophage cell lines are transformed cells that proliferate continuously. The morphological, cytochemical and functional characteristics of all these kinds of cells, as well as their proliferative behavior in vivo and in vitro, show great similarity, although there are also distinct differences.

Origin and kinetics of pulmonary macrophages during an inflammatory reaction induced by intravenous administration of heat-killed bacillus Calmette-Guérin.

This report gives a quantitative description of the kinetics of the pulmonary macrophages and their direct precursors during the acute inflammatory reaction in the lungs induced by intravenous injection of heat-killed bacillus Calmette-Guérin (BCG) into specific-pathogen-free mice. After BCG injection, the total number of pulmonary macrophages isolated by lavage and subsequent enzyme digestion of lung tissue increased to 225% of normal within 12 h and, after a minor decrease, rose to a maximum of 250% of normal at 96 h, followed by a decrease to 150% at 144 h, the end of the observation period. The number of circulating monocytes doubled in the first 48 h and stayed close to that level. In vivo and in vitro labeling with [3H]-thymidine showed that an influx of monocytes transforming into pulmonary macrophages was mainly responsible for the population increase. A temporary increase in the number of locally dividing pulmonary macrophages--manifested by an increased in vitro labeling index, reaching a maximum of 9.6% 72 h after BCG injection--made a minor contribution to the population increase. All pulmonary macrophages were classified according to morphological criteria as alveolar-macrophage-like (AML) or non-alveolar-macrophage-like (NAML), and their respective characteristics were established. The in vivo labeling data showed NAML to represent exudate macrophages derived from circulating monocytes entering the interstitial tissue, and these cells changed morphologically into AML upon entering the alveolar hypophase. This mechanism was confirmed by the finding that the interstitially deposited BCG were found first inside NAML and later in AML. The in vivo labeling data showed that local production was mainly a result of division of macrophages that were morphologically identical with normal alveolar macrophages. The former cells, however, derived most probably recently from the circulation, because the turnover of the total population was very high before local macrophage production became maximal. In mice treated with HC before the injection of BCG, this population increase was absent, because of virtual abolition of the initial monocyte influx and absence of the increased local production of macrophages. Calculations showed that the monocyte influx in the first 48 h amounted to approximately 4 x 10(6) cells, i.e., eight times that found in the normal steady state, and that the efflux of pulmonary macrophages in that period amounted to approximately 3.5 x 10(6) cells, i.e., seven times the normal efflux. The local production over the total period of 144 h was only three times that found normally. The results of these quantitative studies show that the increase of the pulmonary macrophage population during an acute inflammation is brought about mainly by monocyte influx and to a minor extent by a temporary increased local production of macrophages. Disposal of interstitially deposited BCG occurred by phagocytosis by local macrophages and the subsequent efflux of the latter.