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Phages in the international basic set used for routine typing of Staphylococcus aureus were grouped serologically with the indirect haemagglutination inhibition test. The results showed complete agreement with the serological division of these phages into 4 groups: A, B, F and L, which had earlier been done by neutralizing tests. 33 additional phages isolated from 29 Staphylococcus aureus strains of human source were investigated and found to belong to group A or B. Phages of each group were antigenically identical and showed no crossreaction with phages of any other group.

396 Haemophilus influenzae strains were biotyped according to Kilian. 393 of the strains were assigned to biotypes I to V, while 3 strains remained unclassified. Eighty-nine per cent of the capsulated strains produced both urease and ornithine decarboxylase, biotypes I or IV, while 95 per cent of the non-capsulated strains produced only one of the enzymes, biotypes II, III, or V. Of consecutive strains from the upper respiratory tract, the incidence of beta-lactamase-positive strains was higher among capsulated than among non-capsulated strains (p less than 0.025). None of 133 non-capsulated beta-lactamase-positive strains produced both urease and ornithine decarboxylase, in contrast to 15 out of 147 non-capsulated beta-lactamase-negative strains (p less than 0.001). The type e strains were all of biotype IV and 3 of 7 consecutive strains were beta-lactamase-positive.

Antibodies to IgA were detected in two males with hypogammaglobulinaemia. The antibodies were demonstrated to belong to the IgG class. In both patients low serum levels of IgG and IgM but no IgA were found. On two occasions one of the patients reacted with severe side reactions within a few seconds after an intramuscularly given injection of gammaglobulin. The other patient had received monthly intramuscular injections of gammaglobulin over a period of 2 years when the anti-IgA antibodies first appeared and has since then been regularly treated for 1 1/2 years without any signs of adverse reactions. In five additional patients with hypogammaglobulinaemia and side reactions after i.m. injections of gammaglobulin no antibodies to IgA, IgG or Gm-determinants were detected.

Objectives: to investigate the incidence of intraoperative graft contamination, bacterial species and the influence of change of surgeon's gloves on contamination. Design: a prospective randomised study.Materials and methods : forty patients had implantation of synthetic vascular grafts. All patients received intraoperative cloxacillin (2.0 g) or clindamycin (0.6 g) intravenously. The procedures were randomised to two groups: Group 1 – surgeons changed the gloves before the first contact with the vascular prosthesis and Group 2 – operation without glove change. The growth of all bacterial species from graft segments and from the gloves was recorded. The susceptibility to antibiotics was tested.Results : the number of contaminated grafts was similar in the two groups. Growth of bacteria was recorded from 92.5% (37/40) of the graft segments and 33% (51/156) of glove imprints. Of the cultured species, 75% and 47%, respectively, were identified as coagulase-negative staphylococci (CNS). Twenty-eight per cent of CNS were resistant to cloxacillin, 15% to clindamycin, and 10% to cloxacillin and clindamycin. In all, 25% of the CNS strains were resistant to the prophylactic antibiotic used. In 50% of cases, the antibiogram of the CNS strain recovered from gloves agreed with that of the strain harvested from the graft. Conclusions: a high incidence of graft contamination was found which was not reduced by changing gloves. However, changing gloves did seem to reduce the number of bacterial species.

A separation between mecA + strains of Staphylococcus aureus and strains lacking mecA was achieved by the disk diffusion assay and the agar dilution method, utilizing disks containing 5 μg of oxacillin and inocula of approximately 5 × 10 5 CFU/spot, respectively, provided that agar with 0 to 0.5% NaCl and incubation at 30°C were employed. The 5-μg oxacillin disks clearly discriminated between borderline methicillin-susceptible and mecA + strains. The oxacillin MICs were more affected by the inoculum density and salt concentration than were the methicillin MICs, and oxacillin MICs of 4 to 16 μg/ml were obtained for strains lacking mecA . Significantly higher levels of β-lactamase production and reduced oxacillin susceptibilities were recorded for strains lacking mecA , in particular strains of phage group V, when agar with ≥2% NaCl was used than when agar with 0 to 0.5% NaCl was employed. The results indicate that the borderline methicillin-susceptible phenotype is a salt-dependent in vitro phenomenon of questionable clinical relevance.

As part of an intervention project, all patients in Malmöhus county with a culture positive for penicillin-resistant pneumococci, MICor =0.5 mg/L (PRP), have been registered since January 1995. Nasopharyngeal specimens were obtained from family members and close contacts of identified carriers. Children were denied attendance at regular day-care until PRP-negative. In 1995 and 1996, PRP were isolated from 882 individuals, 364 of whom had clinical infection and the remaining of whom were asymptomatic carriers. In 49%, the PRP were of serogroup 9, with MIC of penicillin 0.5-2.0 mg/L and resistance to trimethoprim/sulfamethoxazole. Further analyses with serotyping and genetic fingerprinting suggested strongly that most of the isolates belonged to a single serotype 9V clone. Month by month, an apparently continuous spread appeared from one municipality to a neighboring one. In most communities, the serotype 9V PRP appeared and disappeared within a few months. The active procedures of the intervention project may have limited the spread of the clone in the county.

In a survey of pneumococcal blood isolates from patients in Southern Sweden, 560 isolates were found between 1981 and 1996. Between these years, the incidence of pneumococcal bacteraemia increased from 5.2 to 15.2/100,000/y. The eight most common serogroups/types (14, 7, 9, 6, 23, 3, 4 and 19) accounted for >75% of the isolates, and 96.4% of the isolates were of serogroups/types represented in the present vaccine. A male preponderance (1.17:1) was noted, and the men were younger than the women (mean 57 vs 63 y of age; p

Penicillin tolerance in group A streptococci has been suggested to cause treatment failures in pharyngotonsillitis. In the present study, group A streptococci from patients with pharyngotonsillitis, who healed (n = 33) or failed (n = 25) on phenoxymethylpenicillin therapy for 10 days, as well as isolates obtained following the first (n = 25) and second (n = 7) failure were tested for penicillin tolerance by a plate-screening method. For most strains, the survival rate after a 6-h exposure of log-phase bacteria (10(4) CFU) to a phenoxymethylpenicillin concentration of 4 times the minimum inhibitory concentration (MIC) was below 0.1%. Five strains from cases of failure, exhibiting survival rates of 0.2-0.5%, were subjected to time killing kinetic tests with phenoxymethylpenicillin at 12 times the MIC. At 6 h each of the strains from failures showed survival rates below 0.03%. One single group A strain, previously selected in our laboratory, showed a survival rate of 0.4-1.2%, which was close to tolerance as defined. Four streptococcal strains, earlier reported as tolerant, showed survival rates of1% but were found to be group G. Penicillin tolerance does not significantly contribute to failures in penicillin therapy of group A streptococcal pharyngotonsillitis, but seems to be a common property of group C and G streptococci.

The in-vitro activities of clarithromycin, 14-OH clarithromycin, erythromycin, amoxycillin, metronidazole and omeprazole against Helicobacter pylori were determined at pH 7.2 and 5.5. At pH 5.5 the activities of clarithromycin and erythromycin decreased approximately 16 times while 14-OH clarithromycin was less influenced. Chequerboard titration indicated that the combined activity of clarithromycin and the other compounds was additive.

239 patients with streptococcal pharyngotonsillitis completed treatment with phenoxymethyl penicillin 12.5 mg per kg body weight b.i.d. for 10 days. At examination after completing therapy, throat specimens from 53 patients (22%) yielded growth of group A streptococci of the same. T-type as the initial culture (bacterial treatment failure). 20 of these 53 (38%) had symptoms and signs of tonsillitis (clinical and bacterial treatment failure). 48 of the patients with bacterial failure were randomly allocated to phenoxymethyl penicillin or clindamycin in an open design; 22 of them received a second course of phenoxymethyl penicillin for 10 days and 26 were given clindamycin, 6.5 mg per kg body weight b.i.d. (children) or 300 mg t.i.d. (adults) for 10 days. After completing their treatment, 14 of 22 patients (64%) given phenoxymethyl penicillin harboured the same T-type as in the previous two cultures, while group A streptococci were not recovered from any of the 26 patients receiving clindamycin. In patients with clinical failure after phenoxymethyl penicillin treatment, a new course with this drug is not motivated. In that situation clindamycin seems to be an efficient choice.

The in vitro activity of loracarbef, penicillin V, cefaclor and cefadroxil against log and stationary phase cultures of group A streptococci was compared. MICs and MBCs were determined with the broth dilution method and by a modified agar plate dilution technique where the beta-lactams were inactivated after the MICs were determined allowing inhibited but not killed organisms to grow on further incubation. The MICs of loracarbef and the two cephalosporins were 16-32 times higher than those of penicillin V. In plate dilution the MBC/MIC ratios of all agents were or = 32 for a large number of strains. The phenotype response of stationary phase cultures to beta-lactam antibiotics may not only be related to the physiological status of the streptococci, to the culture conditions and to the beta-lactam under test. The present investigation indicated that the phenotypic response was also an intrinsic property of certain strains.

Sales of antibiotics have increased in Sweden during the past decade. This has been paralleled by an increase in the frequency of beta-lactamase-producing respiratory tract bacteria. To investigate the effects of regional differences in use of antibiotics on beta-lactamase production in respiratory tract bacteria, we collected nasopharyngeal specimens and information about antibiotic use from 1133 children attending day-care centres in four rural municipalities with low use, and one urban municipality with high use of antibiotics, use being assessed from pharmacy sales. The frequency of beta-lactamase production among isolates of Branhamella catarrhalis and Moraxella nonliquefaciens was significantly higher in the urban municipality. This appeared to be a long-term ecological effect of differences in the level of use of antibiotics between the urban and rural populations, rather than an effect of recent antibiotic treatment of individual patients.

Penicillin tolerance in Streptococcus pyogenes has been suggested as a possible cause of therapeutic failure in streptococcal phryngitis treated with penicillin. In 144 patients with acute group A streptococcal tonsillitis treated with phenoxymethyl penicillin 12.5 mg per kg body weight b.i.d. for 10 days the same T-type was recovered after treatment in 21%. The recovery rate was higher for non-tolerant strains, 23%, than for tolerant strains, 10% (p greater than 0.05). Of patients with a non-tolerant strain 17% had both clinical and bacterial treatment failure in comparison with 5% infected with a tolerant strain (p greater than 0.05). Reinfection with a new serotype occurred in altogether 3%. The present data did not indicate that penicillin tolerance in group A streptococci is of significance in acute tonsillitis treated with phenoxymethylpenicillin for 10 days.

purpose: To assess the ecologic impact, in terms of selection of beta-lactamase-producing respiratory tract bacteria, of a single course of peroral beta-lactam antibiotics. patients and methods: One-hundred fifty consecutive children with clinical signs of bacterial respiratory tract infection were randomly assigned to a seven-day course of treatment with either penicillin V, amoxicillin, or cefaclor. Bacteriologic specimens were collected before treatment, at its termination, and at follow-up four weeks later. results: All three drugs investigated caused a similar increase in beta-lactamase-producing bacteria, both in absolute and relative terms, an increase that persisted over a period of at least one month after completion of treatment. conclusion: Penicillin V, amoxicillin, and cefaclor all act as selective agents for beta-lactamase-producing bacteria in the upper respiratory tract. Treatment with a peroral beta-lactam antibiotic puts patients at risk of becoming persistent carriers of beta-lactamase-producing bacteria.

In Malmohus County, Southern Sweden, the frequency of penicillin-resistant pneumococci in nasopharyngeal specimens of outpatients with respiratory tract infections increased from 3.1% in 1993 to 7.6% in 1995, and was thereafter rather stable. Over the period, 82-85% of the patients with penicillin-resistant strains were children 0-6 years of age. Ten groups/types constituted 96-100% of the penicillin-resistant isolates. Grouping/typing of 200 consecutive isolates in October and November each year indicated that the distribution of groups/types amongst patients with respiratory tract infections was rather constant over the period. The frequency of penicillin-resistant pneumococci of groups/types 6, 14, and 19 roughly corresponded to the occurrence of these groups/types amongst the consecutive isolates. Other groups/types 9, 15, 21, and 23 either showed a pronounced increase or decrease, which could not be related to the prevalence of these groups/types among the consecutive isolates or degree of antibiotic resistance. Penicillin-resistant group 9, introduced in the area in 1993, consisted of one single clone, 9V. The stabilized level of penicillin resistance since 1995 may be related to the preventive measures implemented in the area, including day-care interventions, and measures to reduce the prescription rate of antibiotics to outpatients with respiratory tract infections.

In acute tonsillitis, group A streptococci (GAS) is the etiological agent in 30–50% of cases. The reported frequencies of clinical and bacterial treatment failure following penicillin therapy range from 10 to 25%, increasing if treatment is reduced from 10 to 7 days. The MIC value of GAS for penicillin V (pcV) is 0.004–0.03 mg/l by the plate dilution and 0.008–0.03 by the broth dilution technique (2). Resistant strains have not been isolated in vivo but according to some investigations, penicillin tolerance may be one cause of treatment failure (6).

The question whether penicillin V (pcV) given intermittently upon signs of upper respiratory tract infections (URTI) in otitis-prone children might prevent recurrent bouts of acute purulent otitis media (AOM) is addressed. As compared with continuous long-term antibiotic treatment as prophylaxis in otitis-prone children, intermittent administration would reduce the overall consumption of antibiotics. Seventy-six otitis-prone children less than 18 months of age were included in this double-blind, randomized, placebo-controlled multicentre study. Follow-up was from January till June. One hundred and twenty-three episodes of AOM occurred. The number of AOM episodes was reduced by 50% in the children on pcV during URTI episodes as compared with those on placebo. No obvious ecological drawbacks were noted. Thus, the described mode of pcV administration seems to be a rational and safe way to reduce the number of AOM episodes in otitis-prone children.

The susceptibility to penicillin of 6 prevalent pneumococcal types isolated from nasopharynx in 1992 was compared with that of corresponding types from 1980–82. The 6 types or groups, 6, 9, 14, 15, 19 and 23, constituted 78% of consecutive isolates. 19/204 isolates in 1992 were intermediately resistant (MIC 0.12–1.0 mg/1) in comparison with 1/194 from 1980–82 (p < 0.001). Resistant strains (MIC ⩾ 2 mg/1) were not found. Of group 15, no fewer than 10/31 isolates were intermediately resistant, which may support the clonal origin and spread of penicillin-resistant pneumococci. At least 5.0% of nasopharyngeal isolates are now intermediately resistant to penicillin. This figure is substantially higher than the 2% earlier reported in Sweden.

Moraxella catarrhalis and Hemophilus influenzae are isolated from the nasopharynx in 50% to 55% and 8% to 15%, respectively, of cases of acute laryngitis in adults. This finding indicates that these organisms, M catarrhalis in particular, are in some way involved in the pathogenesis of the disorder. In the present double-blind, placebo-controlled trial, the effect of erythromycin ethylsuccinate (0.5 g twice a day for 5 days) on the elimination of nasopharyngeal pathogens and reduction of clinical signs of upper respiratory tract infection, as well as on subjective complaints, was evaluated in 106 adults with acute laryngitis. The bacterial isolation rates at presentation were M catarrhalis 50%, H influenzae 18%, and Streptococcus pneumoniae 4%. In the 99 patients who completed the study, the elimination of M catarrhalis after 1 week was better in the erythromycin group (25 of 30 cases) than in the placebo group (6 of 19 cases; p ≤ .00038). The elimination of H influenzae was unaffected by erythromycin. Otolaryngologic examination did not reveal any significant group differences regarding laryngitis, pharyngitis, or rhinitis. Voice quality was improved after 1 week, irrespective of treatment. However, as compared to the placebo group, the erythromycin group reported fewer voice complaints after 1 week and fewer coughing complaints after 2 weeks. As acute laryngitis in adults is self-limiting, and subjective symptoms are spontaneously reduced after 1 week in most cases, antibiotic treatment does not seem warranted as a general policy. However, erythromycin may be justified in patients who are professionally dependent on voice function.

In Moraxella (Branhamella) catarrhalis and Moraxella nonliquefaciens strains isolated from clinical specimens in the south of Sweden two variants of beta-lactamase were distinguished by isoelectric focusing (IEF). The BRO-1 (Ravasio type) enzyme was the most common in Branhamella catarrhalis, constituting about 90% of the beta-lactamase found in this species, while the BRO-2 enzyme (1908 type) was as common as BRO-1 in Moraxella nonliquefaciens. The determinants mediating the production of BRO-1 and BRO-2 were both transferable by conjugation. Cell-bound beta-lactamase from reference strains producing BRO-1 and BRO-2 could be solubilized by papain digestion. The isoelectric point of the solubilized enzymes differed distinctly between BRO-1 (pI 6.5) and BRO-2 (pI 6.9). The molecular species of BRO-1 and BRO-2 released by papain digestion were purified by affinity chromatography with phenylboronic acid agarose gel. They had identical molecular weights of approximately 28,000. Their kinetic constants were indistinguishable for a number of substrates and beta-lactamase inhibitors.

Previous studies of acute laryngitis in adults have shown high nasopharyngeal isolation rates of B. catarrhalis and H. influenzae. Phenoxymethylpenicillin had no effect on the clinical course. In the present study, 106 patients with acute laryngitis were treated with erythromycin 0.5 g x 2 V or placebo. During the first week the isolation rate of B. catarrhalis was reduced from 60 to 10% in the erythromycin group compared to 34 to 27% in the placebo group (p less than 0.01). The elimination of H. influenzae, isolated in 19% at the acute visit, did not differ between the two groups. As compared to controls, erythromycin treated patients reported significantly lower scores of subjective voice disturbance after 1 week and cough after 2 weeks. Laryngological examination and voice evaluation failed to reveal any differences between the groups.

A novel formula based on broad spectrum antimicrobial drugs for the disinfection and maintenance of human heart valve allografts is presented. The antimicrobial efficiency was evaluated on sixteen aerobic, facultative aerobic and anaerobic bacterial species and 5 species of fungi, all from clinical material. Since 1986 the formula has been used for 66 human aortic and pulmonary valves. The composition and mode of preparation of the antibiotic mixtures, the procedures of disinfection, the outcome of aerobic and anaerobic blood cultures as well as the results of microbiological analysis valves are presented. The principles of valve selection and the criteria for the selection of drugs is described.

30/60 patients electively reconstructed with synthetic arterial grafts were randomly treated with dicloxacillin per- and postoperatively for 6 days. Wound infections occurred in 10 of the non-treated patients. 1 of whom had a graft infection. In the dicloxacillin group no wound infection was recorded. Overgrowth with bacteria resistant to isoxazolylpenicillin was not noticed during treatment. No late infections occurred. In comparison with previous results, improved hygienic routines before, during and after operation reduced the incidence of postoperative graft infections from 15 to 3%. As postoperative infections after synthetic arterial graft implantation are serious complications, per- and postoperative antibiotic treatment seems justified as a complement to a rigorous hygienic routine.

In order to determine the recovery rate of species of the genera Haemophilus and Moraxella (including subgenus Branhamella) from the upper respiratory tract and the incidence of beta-lactamase production within these genera, cultures were made of nose and throat swab specimens and adenoid tissue in 50 children undergoing adenoidectomy. Haemophilus influenzae was isolated from 92% of the children. All children harboured strains of Haemophilus spp. and in 46%, at least one strain produced the TEM-1 beta-lactamase. Branhamella catarrhalis and/or Moraxella nonliquefaciens were isolated from 82% of the children and strains producing the BRO-1 beta-lactamase from 34%. Overall, TEM-1 and/or BRO-1 producing strains were recovered from 60% of the investigated patients. The beta-lactamase production was found to be transferable by conjugation within the respective genera. It is suggested that the apathogenic species may be a source of transferable determinants mediating beta-lactamase production in the upper respiratory tract.

144 industrial workers were investigated for the presence of Staphylococcus aureus in the upper respiratory tract because 53 of them had complained of chronic throat discomfort. Significantly more patients with subjective throat complaints harboured Staph. aureus in the nose (49.1%) and throat (32.1%) than patients without such symptoms (27.4% and 9.9%, respectively). No Staph. aureus were found in throat swab cultures from 21 randomly selected individuals working in a similar factory where no chronic throat discomfort was reported and only 2 throat carriers of Staph. aureus were found among 66 medical undergraduates investigated. The staphylococci belonged to several different phage type patterns and could not be recovered on sedimentation plates or from machines or products. In the light of these and other findings it was suggested that the staphylococci accentuated an already existing damage of the mucous membrane of the throat, but seemed not to be the primary cause of the discomfort.

The plasmid-mediated Branhamella catarrhalis beta-lactamase BRO-1, also found in Moraxella nonliquefaciens, was characterized as regards substrate profile, isoelectric point and relative substrate affinity index (RSAI) to various substrates and compared in these aspects with the TEM-1 enzyme of Haemophilus influenzae. As measured by a biological assay and with high performance liquid chromatography (HPLC), BRO-1 was found to hydrolyse carbenicillin, mecillinam, methicillin and cefaclor with a higher rate than TEM-1. The only substrates having a relative rate of hydrolysis higher for TEM-1 than for BRO-1 were ampicillin and cephaloridine. The rates of hydrolysis registered with these two methods were comparable for all but 2 of 13 tested substrates. Isoelectric focusing yielded a main band at pH 5.6 and several satellite bands consistent with those reported by other authors for Branhamella enzymes having a substrate profile similar to that of BRO-1. A tenfold or higher difference in RSAI between BRO-1 and TEM-1 was recorded for five of the 15 compounds tested. BRO-1 seems to be the most common beta-lactamase in Bran. catarrhalis, irrespective of geographic origin. Its substrate profile, isoelectric pattern and RSAI differ from those of other known plasmid-mediated beta-lactamases described, thus justifying a specific designation.

Infection is a major complication of cerebrospinal fluid (CSF) shunt treatment with a reported incidence of 8-27%. In the present study, comprising 64 patients operated under strictly defined preoperative and peroperative hygienic measures and without use of prophylactic antibiotics, the infection rate was 3.1%. Out of the 2 cases of shunt infection recorded, 1 was probably caused by peroperative contamination and 1 by postoperative, hematogenous spread. Bacterial cultures from the operation area before incision and during operation were negative in 95% and 78%, respectively, and when positive yielded low numbers of organisms. Specimens taken after skin closure revealed growth in 59% and high bacterial numbers in 20%, mostly of Staphylococcus epidermidis and other resident skin bacteria. In addition, cultures of irrigation solutions, kept in open bowls during operation, yielded bacterial growth in 65% with a predominance of S. epidermidis. Thus, the strict hygienic measures did not prevent bacterial recolonization of the wound during operation. It is conceivable that endogenous as well as exogenous spread may be of importance in this context. The contamination of irrigation solutions indicates that closed irrigation systems should be used in this type of surgery.

25 patients with infections with penicillinase-producing methicillin-sensitive Staphylococcus aureus strains were treated by oral administration of flucloxacillin. In 12 of the patients the serum concentration was measured after administration of 0.5 or 1.0 g 3 times a day. After the smaller dose the average serum level was 24 μg/ml in fasting patients and 17 μg/ml in those who had taken the drug in association with a meal. The corresponding values after administration of 1.0 g were 35 and 26 μg/ml, respectively. In both groups the peak serum level occurred, on the average, one hour after intake of the antibiotic. In 14 of 16 patients with deep infections the effect of treatment was regarded as good. In 9 patients with skin infections the effect was initially good. Three of the patients complained of malaise, but the symptom could not be ascribed to the antibiotic.

Varying doses of spiramycin were administered orally to healthy volunteers, and concentrations in serum and saliva were determined. The absorption of the drug was not significantly influenced by concomitant food intake. Saliva peak concentrations were 1.3--4.8 times higher than peak concentrations in serum. The elimination half life was 2--3 h in serum, and 4--8 h in saliva. Accumulation of the drug was seen in saliva but not in serum. The possible effect of spiramycin in eliminating bacteria from the nasopharynx was evaluated in vitro by comparing the spiramycin saliva concentrations with the MICs of bacteria known to establish themselves in the nasopharynx. At a concentration of 1.2 microgram/ml, spiramycin inhibited all investigated strains of group A streptococci, pneumococci and Branhamella catarrhalis, and at 2.4 microgram/ml all investigated gonococci. Concentrations of 19 and 38 microgram/ml, respectively, were required to inhibit all meningococci and Haemophilus influenzae. Following administration of 1.5 g spiramycin as a single daily dose for 3 days, the mean concentration in saliva reached or surpassed the MIC values of streptococci, pneumococci and Branhamella for 45 h, and of gonococci for 25 h. The possible use of spiramycin for prevention of relapses in acute otitis media and in treatment of serous otitis media is discussed, as well as the possible use of the drug in gonococcal and meningococcal nasopharyngeal carriage.

An outbreak in a neonatal intensive care nursery of severe infections caused by Klebsiella pneumoniae type K-17 has been studied. Over a 9-month period 20 epidemiologically linked cases of severe septicemia, meningitis and pneumonia were diagnosed. The specific epidemic strain could be identified. After introduction of a policy of hygienic measures the nosocomial infection could be eradicated although colonization still occurred. Thorough handwashing before and after the nursing care of each infant, individual gowning and disposable gloves in the care of infants below 1 500 g were important. The changing bacterial ecology of a neonatal unit should be followed closely by weekly routine throat cultures as well as by cultures of incubators and ventilation equipment. The present investigation has shown the importance of this procedure, which is mandatory for appropriate choice of antimicrobial agents when treating infections in critically ill or very low birth weight infants in the neonatal intensive care unit. Prophylactic antimicrobial treatment is not indicated. Control of K. pneumoniae nosocomial infections can only be achieved by maintaining a high standard of hygiene in the neonatal care.

Among 250 S. aureus clinical isolates, the incidence of TSST-1 production was 18.0%. S. aureus var. hominis strains were predominant (95.6%), producing high levels of toxin in vitro, within the range of 0.6 to 4.3 micrograms/ml and exhibiting crystal violet binding with C/D pattern. No correlation was found between the level of TSST-1 production in vitro and the clinical course. Two (3.4%) of the var. bovis strains produced toxin in amounts less than 0.6 micrograms/ml and did not bind crystal violet. None of the 24 var. canis isolates produced TSST-1. Fifty five per cent of the isolates of phage group I produced TSST-1 and corresponded to 57.8% of the toxigenic strains. Two of the 250 patients developed toxic shock syndrome.

Branhamella catarrhalis was isolated from the nasopharynx in 55% of 40 noncompromised adult patients suffering from acute laryngitis. Diplococcus pneumoniae and haemophilus influenzae were found in another 5 and 8%, respectively; one patient had group A streptococci in the throat specimen. In 90% of the patients the laryngitis complaints were preceded by symptoms of an acute respiratory tract infection. Two of the patients with B. catarrhalis showed a significant titre conversion against influenza B and parainfluenza type e virus, respectively. Attempts to isolate virus failed in all cases. The results indicate that B. catarrhalis, known to cause acute otitis media in small children and respiratory tract infections in adult compromised hosts, may be involved in the etiology of acute laryngitis in otherwise healthy adults.

The aim of the present investigation was to determine to what extent beta-lactamase producing Haemophilus influenzae (H.i.) and Branhamella catarrhalis (B.c.) were isolated in cases of failure of treatment of acute otitis media (AOM) with phenoxymethylpenicillin. Among children with suspected therapeutic failure referred to an ENT specialist altogether 11, 15% of those referred, fulfilled the criteria of AOM. Three of them were on erythromycin, 1 on ampicillin and 7 on phenoxymethylpenicillin. In 5 of the children treated with phenoxymethylpenicillin H.i. was isolated from middle ear exudate and/or the nasopharynx. All H.i. isolates were non-capsulated and beta-lactamase negative. One beta-lactamase producing B.c. was isolated from the nasopharynx in a patient with pure culture of H.i. in the ear exudate. The present investigation did not support the suggestion that beta-lactamase producing H.i. or B.c. are major causative agents in therapeutic failures of AOM treated with phenoxymethylpenicillin and did not produce any evidence supporting a change from the recommended ampicillin esters/amoxycillin in therapeutic failures.

The plasmid-mediated beta-lactamase in Branhamella catarrhalis (BRO-1), also occurring in Moraxella nonliquefaciens, differs from other known plasmid-mediated beta-lactamases in Gram-negative bacteria regarding substrate profile and isoelectric point. B. catarrhalis strains previously reported to produce beta-lactamases deviating from BRO-1 were tested, and the beta-lactamases did not differ significantly from BRO-1 in substrate profile, isoelectric point or relative substrate affinity index (RSAI). Further investigations of strains of various geographic origin should be undertaken. RSAI seems to be a useful tool for screening of beta-lactamases in B. catarrhalis since values for a large number of strains can easily be determined. The previously reported conjugational transfer of BRO-1 production within species B. catarrhalis and from M. nonliquefaciens to B. catarrhalis was confirmed. Four bands of extrachromosomal DNA were regularly detected by agarose gel electrophoresis in beta-lactamase-producing as well as in beta-lactamase-negative strains of B. catarrhalis and M. non-liquefaciens, provided that the excessive nuclease activity in the preparations was inhibited.

The concentrations of penicillin V were determined in the serum and in ear exudate from children with acute otitis media after oral administration of single doses of 13 mg (20,000 I.U.) and 26 mg (40,000 I.U.) per kg of body weight. The concentration in serum after administration of the smaller dose reached a maximum within 30 min, after which it decreased at a rate corresponding to a half time of 30–45 min. After the larger dose the concentration in serum was highest about 60 min after administration. The concentrations of penicillin V in the exudates after the larger dose reached such values that one might expect the drug to be effective also in most cases of acute otitis media due to Haemophilus influenzae. The method used in the investigation was a modification of the well diffusion method (agar well method) and allowed determination in samples down to a volume of about 0.03 ml. The standard deviation of the method was less than 10%.

Pneumococci isolated from the ear exudate in 245 children under 10 years of age afflicted with acute otitis media were typed. Types 3, 6, 14, 18, 19 and 23 were found in 80% of the cases. In the remaining cases, 15 other types were found. Five strains were not typable with the antisera used. Types 14 and 23 were found twice as often in the age group 0-3 years as in the higher age groups, whereas the opposite was true for type 3. The relapse frequency was highest after types 14 and 19 infections. The frequency of residual secretory otitis was highest after type 14 infections. Types 19 and 23 were never found in infections followed by secretory otitis. Patients with type 14 infections, healed or unhealed, showed the same blood group distribution within the ABO and Lewis systems as a normal Swedish population. Penicillin V therapy failed to eliminate the pneumococcal strain from the nasopharynx in 40% of consecutive cases of otitis media. Relapse after penicillin-treated pneumococcal otitis is to be regarded as a new complication of the primary infection and not as a reinfection from the environment.

Intrageneric and intergeneric conjugational transfer of beta-lactamase production to a Branhamella catarrhalis recipient is described. The branhamella donor strains were fresh isolates subcultured onto penicillin-containing media directly from the primary plates. A beta-lactamase positive Moraxella nonliquefaciens served as donor in the intergeneric matings. The substrate profiles of the branhamella and moraxella enzymes were indistinguishable as determined by biological assays. Excessive endonuclease activity did not permit a conclusive characterization of isolated extrachromosomal DNA from the branhamella donors.

Gentamycin, like the other aminoglycosides, is potentially oto- and nephrotoxic. Despite ten years of clinical experiance it is still not possible to predict the occurrence of oto- and/ or nephrotoxic incidences in a given patient. Vestibular calamities occur unexpectedly, sometimes considerable time after therapy has been discontinued (Jao and Jackson, -64). Renal function impairment, although often slight and transient, seems to be more frequent than was originally supposed (Mosegaard et al., -75). A better understanding of the pharmacokinetic properties of the drug is a necessity to ensure optimal therapeutic effect while at the same time avoiding the oto- and nephrotoxic incidences.

Twenty children with acute pneumococcal otitis media were studied. In 6 children the infection ran a normal course and healed after the first episode and in 14 it relapsed. The serum levels of the immunoglobulins IgG, IgA and IgM were normal in all 20 children. Specific antibodies to pneumococcal polysaccharide were found in all cases, with no differences in the titers between the relapsed cases and those that healed. The complement components were quantitated with electroimmuno assay. C1q proved depressed in 60 per cent of the relapsed cases and in 16 per cent of the healed cases. C1r and Gls were disproportionally high compared with the C1q levels. Furthermore, crossed Immunoelectrophoresis revealed abnormal complexes composed of C1r and C1s, and complexes composed of C1r, C1s and CI IA. These complexes were more pronounced in sera from the children with relapsing otitis media.

Sixty-one patients, aged six months to ten years, with acute purulent otitis media were treated with penicillin V for ten days. The drug was given twice a day in a total daily dose of 50 mg/kg body weight. The concentration of penicillin was determined in serum and in middle ear exudate on one of the first six days of treatment, 60, 120 or 180 minutes after administration of the drug. Bacterial cultures were taken from the nasopharynx before and during treatment and from the middle ear exudate at the time of myringotomy. The serum level of penicillin decreased during treatment. There was also a decrease in penicillin concentration of the middle ear exudate during treatment. This decrease was most pronounced during the first two days. In a few cases Haemophilus influenzae was found in the middle ear exudate during treatment. In these cases the concentration of penicillin in the exudate was found to be higher than the mean concentration at corresponding times. The rapid decrease in the exudate concentration of the drug two to three days after the beginning of therapy may suggest that the patients responded to the treatment and that it is the initial concentration that decides whether an infection will respond to the therapy. High exudate concentrations later on seem to be due mainly to a continuation of the inflammatory reaction and had slight or no clinical effect. Thus, the present investigation produced no strong evidence for a ten-day treatment compared with, for example, a five-day treatment.

Sera from healthy individuals and from patients with staphylococcal infections were examined for anti-alpha-lysin and for antibodies against staphylococcal phage antigens. The phage antigens consisted of purified phages of the serological groups A, B and F, which were adsorbed to tanned sheep erythrocytes. In healthy individuals elevated antibody titres against each of the phage antigens were found in 9–11 per cent and elevated ASta-titres in 1 per cent. Elevated titres against phage antigen group A were found in 71 per cent of the patients. The corresponding figures for antigen group B and F were 25 and 47 per cent, respectively. Elevated ASta-titres were found in 44 per cent of the patients. A four-fold rise of the antiphage antibody titre could occur within 6–14 days in patients with acute staphylococcal infections.

The possible influence of food intake on the bioavailability of metronidazole was examined in ten health volunteers by administration of a single dose of metronidazole on an empty stomach, and with a standardized breakfast. Food intake did not significantly alter the bioavailability of metronidazole. The interindividual variation in bioavailability appeared to be slight. In nine patients with Crohn's disease, the absorption of metronidazole appeared to be reduced and to be more variable than in healthy subjects. In both groups there was a clear relationship between the amount absorbed and dose/kg body weight. Thus, from the pharmacokinetic point of view, metronidazole can safely be given either with or between meals. The dose should be related to body weight.

Four qualitative methods for the detection of beta-lactamase production in Staphylococcus and Micrococcus species were evaluated and compared with a quantitative macroiodometric reference method. The disc diffusion test with penicillin G and the cloverleaf method could not separate beta-lactamase-positive from beta-lactamase-negative strains. Two applications of the chromogenic cephalosporin test, using uninduced strains and strains grown on blood agar plates, gave a large number of false negative and false positive results. False negative reactions were most common among uninduced strains, while the false positive reactions were most often recorded for Staphylococcus saprophyticus. A high degree of efficiency was recorded for the nitrocefin spot test, using induced strains grown on antibiotic susceptibility agar, and for the starch-iodine plate method. The starch-iodine plate with methicillin as inducer gave the most reliable results.