Christer Lundberg

Impact of Cefaclor on the Normal Human Oropharyngeal and Intestinal Microflora

Cefaclor was given orally in doses of 250 mg every 8 h for 7 days to 10 volunteers. Saliva and faecal specimens were taken up to 16 days for cultivation of aerobic and anaerobic microorganisms and for assay of cefaclor. Cefaclor was not detected in saliva or faeces. In the oropharynx only minor changes in the anaerobic part of the microflora were observed. The microflora was normalized within 1 week after the administration of cefaclor had stopped. The aerobic intestinal microflora was unchanged during and after cefaclor administration while a minor impact on the anaerobic intestinal microflora was observed. The anaerobic intestinal flora returned to its normal state within 1 week. No new colonization with cefaclor resistant microorganisms were observed and no side effects were registered during the investigation period.

Imprints from the oropharyngeal mucosa: a novel method for studies of cell-kinetics and spatial relations between leukocytes, epithelial cells and bacteria in the secretion on the surface of the mucosa

Cell-kinetics and spatial relations between the cellular elements in the secretion on the mucosal surfaces of the oral cavity and the pharynx were studied with a new imprint technique whereby pieces of foam-plastic are pressed against the mucosal surfaces and then immediately against a glass slide. For visualisation of leukocytes, epithelial cells and bacteria, imprints were stained according to May Grünewald-Giemsa and with acridine orange. For visualisation and discrimination between T and B-cells, slides were stained with immunohistochemical technique using anti-CD-3 and anti-CD-19, respectively, as antibodies. Imprints were also prepared for scanning electron microscopy (SEM). The results show that there are large numbers of morphologically intact cells in the secretions and that there are statistically significant differences between the different mucosal areas as regards numbers, types and spatial relations between the cellular elements in the surface secretions. Rather great inter- and intra-individual differences in cellular composition were observed, indicating a dynamic system. This was further documented by observation of a dominance of polymorphonuclear leukocytes on the tonsillar surface, in contrast to the dominance of mononuclear leukocytes in secretion from the mesopharynx. We consider that this new imprint method is reliable and gives representative samples from the surface secretion. The results clearly show the need for further studies concerning the physiological role of the cellular elements in the surface secretion of the oral cavity and mesopharynx.

Acute pharyngotonsillitis is an infection restricted to the crypt and surface secretion.

A commonly accepted hypothesis is that acute pharyngotonsillitis is caused by bacteria which first adhere to the epithelial surface and then invade the tonsillar parenchyma; however, evidence directly supporting this hypothesis is not available. In previous studies on acute pharyngotonsillitis, we found that the secretion in crypts and at the surface was infected in acute pharyngotonsillitis while no bacteria were detected in the parenchyma. Based on these results, we have proposed a new hypothesis stating that the infection is restricted to the crypt and surface secretions in acute pharyngotonsillitis. To evaluate this hypothesis further, in the present study we examined tonsillar tissue and secretion from patients with acute pharyngotonsillitis, recurrent pharyngotonsillitis and healthy tonsils. Surface secretion was studied after sampling by an imprint technique followed by routine histological preparation. Tonsillar tissue was examined by fluorescence microscopy after staining with acridine orange and by transmission electron microscopy. There were high numbers of bacteria and moderate or extensive ongoing phagocytosis in the crypt and surface secretion from patients with acute pharyngotonsillitis. Bacteria, leucocytes and phagocytosis were also present, but to less extent in the secretion from patients with recurrent pharyngotonsillitis and to even less extent in the healthy controls. In none of all the investigated tonsils were bacteria present in the parenchyma. Bacterial adherence to the epithelial surface was only very rarely observed. This study supports the hypothesis that acute pharyngotonsillitis is an infection restricted to the crypt and surface secretion and that bacterial adherence is not of significant importance in the pathogenesis of acute pharyngotonsillitis.

Double-blind comparison of cefixime and cefaclor in the treatment of acute otitis media in children

In a double-blind study cefixime, an oral cephalosporin of the third generation, was compared to cefaclor in the treatment of acute otitis media in 397 children aged 6 months to 12 years. Clinical evaluation was carried out at the beginning, at day 10-12 and day 28-35 after the start of the treatment. Specimens for bacterial culture and sensitivity testings were taken from the nasopharynx at the initial visit. Patients were randomized either to cefixime in a dose of 8 mg/kg/day or cefaclor in a dose 40 mg/kg/day in the proportion of 2 cefixime patients to 1 cefaclor patient. Two daily doses were administered for 7 days. At day 10-12, 93.5% in the cefixime group and 90.5% in the cefaclor group (p = 0.08) were clinically cured or improved. At day 28-35 the rate of cured or improved patients had decreased, mostly due to reinfections, to 90.1% in the cefixime group and to 86.6% in the cefaclor group (p = 0.12), respectively. 375 patients (69.9%) had positive bacterial culture in the nasopharynx of at least one strain of Haemophilus influenzae, Streptococcus pneumoniae, Branhamella (Moraxella) catarrhalis or combinations of these 3.73.6% of the B. catarrhalis strains were beta-lactamase producing and 11.4% of the H. influenzae strains, respectively. All isolated bacteria were sensitive to cefixime. Adverse events were reported in 17.9% in the cefixime and 10.6% in the cefaclor group. Most reactions were of moderate or mild nature and mostly affected skin or the gastrointestinal region. No serious adverse experiences occurred. In view of the good clinical results obtained cefixime seems to be at least as effective as cefaclor in the treatment of acute otitis media in children.

Phagocytosis in the nasopharyngeal secretion by cells from the adenoid

The aim of this study was to elucidate whether granulocytes and macrophages in surface secretion on the adenoid emanate from the adenoid and whether these cells participate in the control of the nasopharyngeal bacterial flora. Samples of the adenoid and its surface secretion were obtained during adenoidectomy from 12 children with recurrent acute otitis media, secretory otitis media or enlarged adenoids causing obstruction. Immunochemistry was used to examine the location of granulocytes and macrophages in the adenoid as well as the presence of IgA, IgM, IgG and plasma cells in the secretion. Phagocytosis in the secretion was examined in imprints stained with May-Grünwald Giemsa. Acridine Orange and Gram staining were used to demonstrate the presence and location of bacteria in the secretion and mucosa. As a control, surface secretions were obtained from 12 children without any history of recurrent airway problems. Granulocytes and macrophages were observed in the epithelium of the adenoid and some of these cells penetrated the epithelial surface. Positive staining for IgA, IgM and IgG was observed in all secretions. In 10 of 12 children plasma cells were present in the secretion. Bacteria were observed in all imprints. With the exception of 1 child in each group phagocytosis of bacteria in the surface secretion was demonstrated from imprints in all children. We conclude that granulocytes and macrophages leave the adenoid and enter the surface secretion, where constant phagocytic activity takes place. The spatial relations between mononuclear and polymorphonuclear cells imply a possible cooperation between these cells in the overall control of the nasopharyngeal bacterial flora.

Low Secretory IgA Concentrations in Oral Secretions during the Acute Phase of Infectious Mononucleosis

Although the Epstein-Barr virus (EBV) relation to infectious mononucleosis (IM) has been well established, the question why IM is not compulsory during a primary EBV infection has yet to be solved. Assuming a possible oropharyngeal secretory immunoincompetence as an etiological component of IM, the secretory IgA concentrations in oral secretions during the acute phase of IM was investigated. Low concentrations of secretory IgA in IM patients (n = 18) were found, mean value 0.180 g/l as compared to those in healthy controls (n = 10), mean value 0.680 g/l. Furthermore, diminishing concentrations of secretory IgA were found during the acute phase of IM. There was no corresponding serum IgA decrease. The investigation also revealed that tinidazole, claimed to be beneficial in the treatment of anginous IM, did not affect the concentrations of spit secretory IgA.

Chemotactic properties of retained maxillary sinus secretions.

The chemotactic activity of 82 aspirated maxillary sinus secretions obtained from 32 sinuses in 29 patients was assayed with a modified Boyden chamber technique. The secretions were also analysed with respect to the proteolytic activity according to a modification of a technique described by Moroz. In only 3 of 24 sinus secretions obtained from untreated patients with purulent or mucopurulent sinusitis, but in 5 of 8 serous secretions from untreated patients with serous sinusitis a chemotactic activity exceeding random migration was found. A high proteolytic activity was found to be incompatible with a high chemotactic activity. Regarding mucopurulent and purulent sinusitis, treatment by repeated antral aspiration resulted in an increase of the proportion of chemotactically active secretions and a decrease of the proteolytic activity. Repeated antral aspirations in patients with serous sinusitis resulted in less uniform changes of the chemotactic activity.