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This consensus document sets out proposals for antibiotic prophylaxis in abdominal, urological, gynaecological, orthopaedic, vascular and thoracic surgery. As far as possible the recommendations are based on prospective controlled trials. However, for some procedures, e.g. lung surgery and implantation of pacemakers, documentation is lacking but antibiotic prophylaxis is given traditionally. The choice of antibiotics is generally conservative, emphasizing that antibiotics used for therapy should be avoided in prophylactic regimens. Most recommendations are for the use of a first- or second-generation cephalosporin or an isoxazolyl penicillin, when necessary, combined with a nitroimidazole derivative (metronidazole or tinidazole). Suggestions are given for more frequent use of orally administered antibiotics, such as co-trimoxazole, doxycycline, metronidazole or tinidazole. Emphasis is put on short-term prophylaxis. In most cases surgical antibiotic prophylaxis should be given as a single dose and in no case should the prophylaxis time exceed 24 h. [ABSTRACT FROM AUTHOR]

A nationwide study of invasive group A streptococcal (GAS) infections in Sweden during 1994-1995 was carried out. All Swedish microbiological laboratories were asked to report isolates of GAS from normally sterile sites. During the study period they were also asked to send their isolates for T typing. Questionnaires were sent to the physicians in charge of each patient. The incidence, serotype, clinical presentation, symptoms and outcome were recorded. Clinical data were obtained for 468 of 556 patients with GAS bacteraemia. The lethality rate was 16%, but was much higher (37%) in the 113 patients who developed streptococcal toxic shock syndrome (STSS). Streptococci of serotype T1 dominated during the study period and were linked to the increase in invasive GAS infections. They also carried an increased risk of causing STSS. Invasive streptococcal disease with STSS most often has an unknown primary focus or is associated with soft tissue infections. Invasive streptococcal disease not associated with STSS most often has a skin infection as portal of entry or else an unknown focus.

Considerable knowledge has been accumulated regarding the characteristics of acute post-streptococcal glomerulonephritis (APSGN), and many attempts have been made to identify a streptococcal factor or factors responsible for triggering this disease. However, the pathogenic mechanism behind APSGN remains largely unknown. As glomerular deposition of C3 is generally demonstrated before that of IgG in the disease process, it is likely that the inflammatory response is initiated by renal deposition of a streptococcal product, rather than by deposition of antibodies or pre-formed immune complexes. During recent years, a number of streptococcal products have been suggested to be involved in the pathogenic process. In this review, possible roles of these factors are discussed in the context of the clinical and renal findings most often demonstrated in patients with APSGN. Streptokinase was observed to be required in order to induce signs of APSGN in mice, and a number of findings suggest that the initiation of the disease may occur as a result of renal binding by certain nephritis-associated variants of this protein. However, additional factors may be required for the development of the disease.

The intrafamilial spread and recurrence of group A beta-haemolytic streptococci (GAS) infections was investigated. The evaluation was based on 114 patients and their families treated with penicillin for 5 days and followed for 1 month. GAS of the same T-type as that of the isolate from the index case were found in other family members in 33% of the families. Genetic finger-printing using RFLP was performed on 33 of the isolates. The mothers dominated among the index cases, 40 patients experienced recurrences, 27 of them were clinical 28 recurrences occurred within 10 days after the end of treatment. Of 20 T-typed patients with early clinical treatment failures, infected family members were detected in 16 families (p < 0.001). In 19% of the patients GAS could be isolated from the nose. These patients had more ill family members than did other patients. An extensive intrafamilial streptococcal spread was found. Most recurrences of GAS pharyngotonsillitis after penicillin treatment are probably due to "ping pong" infection from family members.

In a randomized, placebo-controlled, double-blind, multicentre study, 130 patients with recurrence of group A beta-hemolytic streptococci (GAS) and clinical signs of pharyngotonsillitis were enrolled. The patients received antibiotic treatment for 10 days, followed by 10 days of alpha-streptococci-inhibitory to GAS-or placebo spray treatment. Patients taking antibiotic treatment for at least 9 days and using the spray for at least 5 days were included in the efficacy analysis. In addition, recurrence within the first 5 days of spray treatment was classified as 'early treatment failure'. The clinical recurrences (bacteriologically verified) in the alpha- (n = 51) and placebo-treated (n = 61) patient groups were 2% (n = 1) and 23% (n = 14) respectively, in patients given spray for at least 5 days (p = 0.004). The inclusion of 'early treatment failures' reduces this difference (p = 0.064). Both treatments were equally well tolerated. Thus, alpha-streptococci given as a spray and used for at least 5 days significantly prevented recurrence of GAS pharyngotonsillitis.

The efficacy of cefuroxime axetil compared with phenoxymethylpenicillin (PcV) was studied in group A beta-haemolytic streptococci (GAS) culture-proven tonsillitis in children aged 3-12 years with a history of at least 1 episode of tonsillopharyngitis requiring antibiotic therapy during the previous 3 months. This was a comparative, randomized, investigator-blind, multicentre study. A total of 236 children received either cefuroxime axetil suspension or PcV syrup. Inclusion criteria were a positive, rapid, group A strep test verified by bacteriological culture and clinical signs and symptoms of tonsillopharyngitis. Cefuroxime axetil treatment gave a significantly higher bacteriological eradication rate and clinical cure rate than PcV. At day 2-5 post treatment the eradication rates were 99/114 (87%) for cefuroxime axetil vs 61/109 (56%) for PcV (p < 0.001). The clinical cure rates were 98/114 (86%) and 73/109 (67%) respectively (p < 0.01). Up to 21-28 days post-treatment, 9/114 (8%) cefuroxime axetil patients and 37/109 (34%) PcV patients were treatment failures or had recurrence/reinfection of GAS tonsillopharyngitis (p < 0.001). More than 90% of the patients who experienced bacteriological treatment failure at either the first or second follow-up had the same serotype isolated pre- and post-treatment. During the study period, 21/114 (18%) patients in the cefuroxime axetil group and 50/109 (46%) patients in the PcV group received additional antibiotics (p < 0.001). No serious adverse events were noted and the mild adverse events were equally distributed among the patients in the 2 study groups: 15% for cefuroxime axetil and 14% for PcV.

The multiorgan failure syndrome caused by group A streptococci (GAS) designated streptococcal toxic shock syndrome (STSS) is believed to be mediated by cytokines induced by superantigens. In order to study the relationship between superantigen production, cytokine levels in patient sera, and clinical GAS manifestation we examined acute-phase sera and strains from 25 patients with GAS bacteremia. The patients had various disease manifestations, including STSS (44%), erysipelas (28%), septicemia (24%), wound infections (16%), and pneumonia (12%). Serotype T1M1 dominated, representing 56% of the isolates, but also strains of other serotypes were identified. The strains were found to produce the streptococcal pyrogenic exotoxins (Spe) A, B, and F, as determined by immuno-blot analyses. There was no difference in amounts of toxin produced between strains isolated from patients with different manifestations of disease. Levels of TNF alpha, IL1 alpha, IL6, IL8, and IFN gamma in acute-phase sera were determined by use of ELISA and RIA assays. The analyses showed higher levels of IL6 in sera from patients with STSS than in sera from patients with bacteremia without shock. TNF alpha was elevated in sera from patients with STSS, as compared to sera from patients with uncomplicated pharyngotonsillitis. No increase in the levels of IL1 alpha, IL8, and IFN gamma could be found in the patient sera and there was no difference in the level of those cytokines between the various patient categories.

Recurrences are a common finding after antibiotic treatment of acute group A streptococcal tonsillitis. This has been attributed to several factors, among others a disturbed normal throat flora and especially a lack of alpha-streptococci. It thus seems logical in patients with recurrent streptococcal tonsillitis, to restore the normal alpha-streptococcal flora by reimplantation of alpha-streptococci. This was performed in a double blinded, randomized, placebo-controlled study. 36 patients with recurrent streptococcal group A tonsillitis were treated with antibiotics followed by either placebo (19 patients) or a pool of 4 selected alpha-streptococcal strains (17 patients) with good interfering activity against clinical isolates of beta-streptococci. No patient recurred during the first 2 months of follow-up in the alpha-treated group, but 7 in those treated with antibiotics and placebo. After 3 months 1 in the patient group treated with antibiotics and alpha-streptococci and 11 in the placebo-treated group recurred. These results are statistically highly significant and show that recolonisation with alpha-streptococci seems to offer a new way to lower the rate of recurrence in streptococcal throat infections.

During 1988 and 1989 > 500 cases of serious group A streptococcal infections were reported in Sweden, many with a fatal outcome. We report here on 11 consecutive patients with septic preshock/shock and multiorgan failure, including acute renal failure. 10 had verified group A streptococci (GAS) serotype T1M1 infections while 1 patient was culture negative but with clinical signs of severe infection and serological evidence of GAS infection. Presenting symptoms were high fever, relative bradycardia, edema and renal failure. In all patients the condition deteriorated despite conventional treatment including volume substitution and antibiotics. Systolic blood pressure was transiently < 80 mmHg in 10 patients and 9 of them needed infusion of inotropic agents to avoid fatal circulatory shock. In 9 patients respiratory aid was instituted and 7 were dialysed. Plasma exchange was performed in 7, while the remaining 4 received transfusions with blood and plasma without plasma exchange. 10 patients improved and were discharged within 8 weeks. One woman died within 2 days after admission to the hospital. Renal function recovered in all survivors, with a follow-up serum creatinine < 80 mumol/l. The complicated clinical picture in these patients with many simultaneous therapeutic events confounds the interpretation of the effect of single actions. The favourable outcome in these severely ill patients suggests that potent inotropic agents, immunoglobulin therapy and plasma exchange might be beneficial in severe streptococcal disease when conventional treatment fails.

A case of recurrent pyogenic arthritis in a knee joint and abscess formation of the lower limb is described. The infection occurred in a 70-year-old male patient treated with steroids for rheumatoid arthritis. A strain of Bacteroides fragilis was repeatedly isolated both from the knee joint and the abscess. The isolated strain was used as antigen in tube agglutination tests and significant titre changes were observed during the course of the disease. The isolated strain was initially sensitive to doxycycline but developed resistance to this drug during therapy. The sensitivity to lincomycin remained unaffected.

The penetration and distribution of labeled benzylpenicillin and cefuroxime into normal and infected rat brain was studied. 15 rats were injected intravenously with radiolabeled antibiotic; 5 of these served as uninfected controls and 10 were previously infected by stereotactic deposition of 10(11) B. fragilis in the right frontal lobe inducing bacterial cerebritis. The animals were killed after administration of antibiotic. The brains were immediately frozen and cut into 20/micron sections. Autoradiographic recordings showed that benzylpenicillin was mainly distributed in the cerebrospinal fluid and pial vessels but no activity was found in the deeper grey or white matter. In contrast, cefuroxime was found not only in the surrounding but also in the centre of the infected area. The autoradiographic technique provides a valuable method for studies of the distribution of antibiotics in the brain.

Dicloxacillin was administered as 2 g single intravenous doses to healthy young and old subjects of both sexes aged 19-32 years and 65-76 years, respectively, and the pharmacokinetics were studied. Peak serum concentrations were higher in young than in elderly subjects and in each age group in females than in males. The elimination rate was similar in all groups and the only striking pharmacokinetic differences observed were that the urinary recovery of active dicloxacillin was higher in young subjects and that the non-renal clearance was higher in elderly volunteers. The findings were interpreted to be due to a systemic metabolism of dicloxacillin, compensating for a reduced renal elimination in the elderly subjects. In all subjects dicloxacillin was well tolerated. No increases of serum creatinine were observed.

The pharmacokinetics of ampicillin and dicloxacillin following intravenous injection was studied in a tissue cage model in rabbits. Serum protein binding was 98.6% for dicloxacillin and 46.7% for ampicillin, and there were no major differences between the degree of binding in tissue case fluid. The highly bound dicloxacillin gave lower but more sustained levels in tissue cage fluid than ampicillin, and showed a very long elimination half-life. The findings suggest that the flow of albumin into the interstitial space could be of importance for the tissue penetration of highly protein bound antibiotics. The results also indicate dose-dependent pharmacokinetics for dicloxacillin.

17 primary health care (PHC) centres participated in a 1-month evaluation of a county urinary tract infection (UTI) management program. A total of 302 patients contributing 355 episodes, dominated by female (93%), lower symptomatic (75%) and Escherichia coli (74%) episodes were studied. In therapeutic failure gram-negative bacteria other than E. coli showed an increased prevalence whereas Staphylococcus saprophyticus was not found. The general pattern of drug resistance was little influenced by UTI history and the mean pretherapy prevalence of resistance to the 7 antibacterial agents studied was low (7%). Drug resistance was increased in failure (mean 24%) also for agents not used for therapy (sulphonamides and nitrofurantoin) but not in early or repeated recurrence. UTI symptoms were eradicated in only two-thirds of bacteriologically cured episodes but in one-third of the failures at the posttreatment control. On average, therapy resulted in 8% bacteriological failure and 12% early recurrence. The bacteriological cure rate was the same irrespective of whether the infecting bacteria were classified as sensitive or resistant in vitro to the drug given. Thus, sensitivity testing of isolates is rarely needed in sporadic or recurrent UTI in PHC but may be relevant in failure. In order to be of prognostic value in uncomplicated UTI high-level breakpoints focusing more on peak urinary drug concentrations need to be studied.

A new experimental model to evaluate the postantibiotic effect (PAE) in vivo was developed using subcutaneously implanted tissue cages in rabbits with normal host defence mechanisms. The rabbits received benzylpenicillin i.v. in a dose giving a free penicillin concentration of 10 X MIC in the tissue cage fluid (TCF). A log-phase suspension of group A streptococci was injected into the tissue cages exposing them to penicillin in vivo. After 2 h bacterial samples were withdrawn, treated with penicillinase and transferred to 2 tissue cages in untreated rabbits. Simultaneously, unexposed streptococci were implanted in 2 other cages in the same animals. By repeated sampling of TCF, growth curves of the streptococci exposed to penicillin and the controls could be compared and a PAE of 1.6-2.4 h demonstrated. The PAE was of the same magnitude as that found in vitro. The model has several advantages for the demonstration of PAE in vivo: repeated samplings are easy to perform percutaneously, the effect of subinhibitory antibiotic concentrations are avoided, interindividual variations are eliminated since each animal is its own control, and the experiments can be performed in animals with undisturbed host defence mechanisms.

11 patients with moderate infections were treated with bolus injections of tobramycin in a fixed dose of 4.5 mg/kg and day for 8 days. The patients were randomized to injections every 8 h (TID) for 4 days followed by injection every 12 h (BID) or vice versa. Serum concentrations were measured on day 2 of each regimen. The TID regimen gave peak levels less than 4 micrograms/ml in 5/11 patients, mean value 4.2 micrograms/ml. With the BID regimen 2 patients had peaks less than 4 micrograms/ml, mean value 5.9 micrograms/ml. The BID regimen seems preferable when treating patients with normal renal function. The bolus injections were well tolerated.

Out of 169 patients with streptococcal tonsillitis treated with phenoxymethylpenicillin, 13 (8%) developed a new clinical infection with the same streptococcal strain within 2 weeks of completing the therapy (clinical treatment failure) and 24 (14%) were clinically healthy but harboured the same streptococcal strain after treatment (bacterial treatment failure). Patients with clinical treatment failure showed beta-lactamase activity in their saliva pellet significantly more often than patients with bacterial treatment failure, healed streptococcal tonsillitis or non-streptococcal tonsillitis as well as healthy controls. In an interference study, clinical treatment failures were compared with healthy streptococcal carriers, i.e. persons living in the same household and harbouring the same beta-streptococcal strain. 11/12 healthy carriers had alpha-streptococci with interfering activity against their own beta-streptococcal strain, while the corresponding figure for the clinical treatment failures was 2/13. Furthermore, 6/12 healthy carriers had beta-streptococci inhibiting their own alpha-strains, while the streptococci in 11/13 clinical treatment failures had this ability. The beta-lactamase activity and the interference between alpha- and beta-streptococci may be a contributory cause to treatment failure in streptococcal tonsillitis.

The study was designed to analyse the effect of penicillin on interference between alfa-streptococci and group A streptococci in vivo. Tissue cages were implanted subcutaneously in 9 rabbits and inoculated with 10(5) cfu of alfa- and beta-streptococci together as well as separately. Both streptococci were recovered 96 h after the inoculation in the untreated rabbits. Alfa-streptococci inhibiting the growth of beta-streptococci in vitro retained this capacity under the experimental in vivo conditions. Higher penicillin concentration did not increase the killing rate of beta-streptococci grown separately while a faster killing was observed with low penicillin levels in the presence of inhibiting alfa-streptococci, indicating synergistic effect.

200 patients with primary impetigo were studied. Staphylococcus aureus was the only organism isolated in 72.5%, beta-hemolytic streptococci, group A, in 10%, and both pathogens in 15%. 17 of the 50 streptococcal isolates were typed serologically; 11 of these belonged to potentially nephritogenic types. A majority of these cases had identical strains in the nose and throat. Hence, the primary source of skin streptococcal in this study may be the nasopharynx. Uncomplicated cases were treated with topical antibiotics, and oral antibiotics were added in 22 cases with extensive lesions, fever or a concurrent throat infection. None of the 200 patients developed acute glomerulonephritis and urinary analyses were normal at follow-up after 3 weeks.

The in vitro susceptibility to gentamicin, tobramycin, amikacin and netilmicin in septicaemia isolates was followed during 1980-1984 in 6-8 Swedish laboratories. The bacterial distribution was similar over the years and was dominated by Escherichia coli and staphylococci. Resistance to gentamicin was found in 2.3-3.6%, to tobramycin in 1.4-3.4%, to amikacin and netilmicin in 0.5-0.9%. Production of aminoglycoside modifying enzymes was observed among resistant strains.

Studies on the streptococcal epidemiology of impetigo in children below 12 years of age in Addis Ababa indicated that most streptococci isolated belonged to the classic serological impetigo strains. Streptococcal type 9 seemed to be a new impetigo strain. Several cases of severe acute glomerulonephritis on impetigo basis were observed during the study.

Beta-streptococci isolated from patients with acute tonsillitis were tested for penicillin tolerance defined as an MBC/MIC ratio greater than or equal to 16. 11/18 strains recovered from patients with clinical treatment failure were tolerant to penicillin in comparison with 0/15 strains from successfully treated patients. The MBC/MIC ratio was less than 16 for all strains versus cefadroxil but above that ratio for many strains versus clindamycin, doxycycline and erythromycin. We suggest that penicillin tolerance may be one reason to treatment failures in individuals with streptococcal tonsillitis and that other antibiotics could be used to treat these patients since penicillin tolerance is not correlated to a general increase in antibiotic resistance.

A neurosurgical patient with postoperative meningitis caused by Serratia marcescens was treated with intraventricular as well as intramuscular gentamicin. Gentamicin concentration in serum and CSF was determined at different times after the administration. Serratia marcescens could not be isolated from CSF after 3 days of therapy. Determination of gentamicin concentrations in CSF showed that gentamicin should not be given intraventricularly more than once a day to avoid accumulation of the drug. No adverse effect was noticed although the CSF concentration reached 450 mug/ml.

The penetration of various aminoglycosides into uninfected and infected fluids of steel net cages, implanted subcutaneously into rabbits, was studied. The pharmacokinetics of the antibiotics tested in these fluids were characterized by a peak concentration which was delayed in relation to that in serum after both intramuscular and intravenous administration, and by a slower elimination from cage fluids than from serum. Comparing amikacin, gentamicin, netilmicin and tobramycin, the latter seemed to have a somewhat lower penetrability into uninfected cage fluids. Infection of the cage fluids with gram-negative aerobic bacteria resulted in a reduction of the measurable concentrations of amikacin, gentamicin or netilmicin in the cage fluids when compared to those obtained in uninfected fluids in the same rabbits. Elimination of the aminoglycosides from the infected cage fluids was slower than from the uninfected ones. The lower concentrations of the aminoglycosides in infected cage fluids were considered to be primarily due to a penetration barrier created by the infection. The viable counts in infected cage fluids were only marginally affected in cages where the aminoglycoside concentrations were above the minimum inhibitory concentrations (MIC's) of the aminoglycosides against the bacterial strains used for infection when tested in vitro according to standard techniques. In infected cage fluids the pO2 and pH were low, while the pCO2 was high. The number of viable bacteria was high. These factors, which in vitro increased the MIC's of the agents, and the low concentrations achieved in infected cage fluids could explain the inefficacy of aminoglycoside treatment in this experimental model.

The aim of the investigation was to study the influence of various penicillin levels on the interference between alfa- and beta-streptococci based on antibiotic levels registered after oral intake of penicillin tablets. It was found that penicillin was released from ordinary sugar coated tablets already in the mouth resulting in concentrations in saliva above the MIC of most penicillin sensitive microorganisms during the first 2 min. This was followed by a decrease of the alfa-streptococcal flora. It was also shown that penicillin levels above the MIC of alfa-streptococci resulted in prolonged survival of beta-streptococci as compared to that noted at penicillin levels above the MIC of beta-streptococci but below that of the alfa-strains. At this latter level a synergistic effect between penicillin and interfering alfa-streptococcal strains could be demonstrated.

27 patients, aged 19-23 yr, with symptomatic urinary tract infection or epididymitis due to Pseudomonas aeruginosa were treated with azlocillin. All pseudomonas strains were sensitive to azlocillin. The microorganism was eradicated in 25/26 evaluable patients. 25/27 patients were clinically cured. Bacteriological relapse occurred in 11 patients. No serious drug reactions were noted.

The pharmacokinetics of phenoxymethylpenicillin in tonsillar tissue was studied in 33 patients who underwent tonsillectomy, mainly because of repeated tonsillitis or peritonsillitis. The patients were operated on 30-240 min after an oral penicillin dose of 12.5 mg/kg body weight. The mean serum concentration was 2.8 micrograms/ml for 10 patients operated upon 80-95 min after drug administration. The mean tissue concentration for these patients at the same time was 0.6 micrograms/g. The mean concentration of penicillin in tissue after 240 min was 0.05 micrograms/g. 19% of the serum concentration was recovered in the tonsillar tissue. No significant difference between penicillin concentration in the centre or surface of the tonsils was found. The tissue concentration was calculated to be above 0.03 micrograms/ml for at least 4-5 h. 30% of the patients harboured penicillinase producing bacteria on their tonsils, mainly Staphylococcus aureus. These patients had a lower tissue concentration than those lacking the bacteria, but the difference was not statistically significant (p = 0.095).

13/169 outpatients (8%) with streptococcal tonsillitis developed a new tonsillitis with the same strain within 2 weeks of completion of therapy (clinical treatment failures) and 24 (14%) remained carriers (bacterial treatment failures) after treatment with phenoxymethylpenicillin (penicillin V) 12.5 mg/kg body weight twice daily for 10 days. The mean serum concentration 60 min after penicillin V administration was 7.84 micrograms/ml. Very large individual differences in serum concentration were found but these differences could not be correlated to treatment failure. About 60% of the patients showed salivary concentrations around 0.03 micrograms/ml. Three strains of streptococci (groups C and G) from patients with bacterial treatment failure had MIC values of 0.06 and 0.12 micrograms/ml. A majority of the patients with clinical treatment failures had contact with individuals with high carrier rates of beta-hemolytic streptococci. It therefore seems likely that some so-called treatment failures in reality are new infections. In clinical treatment failures group A streptococci were twice as common as groups C + G. In bacteriological treatment failures the ratio between A and C + G was 1:1. Patients with nonstreptococcal tonsillitis as well as carriers of groups C and G may appear among bacterial treatment failures.

Paired sera from 97 patients with acute maxillary sinusitis were examined regarding antibodies to Branhamella catarrhalis. Precipitating antibodies were demonstrated in almost all sera both from patients and from healthy blood donors. Complement-fixing (CF) antibodies to B. catarrhalis were present in sera from 25 of the 97 patients and in one of 20 healthy blood donors. The titres were low and the titre changes when present were of a small magnitude. CF antibodies were most commonly demonstrated in the younger age groups. The patients with demonstrable CF antibodies to B. catarrhalis did not differ from patients without antibodies regarding radiological appearance or healing during therapy. Strains of B. catarrhalis were all rapidly killed by normal human serum but not in heated sera. The strains could not multiplicate significantly at an oxygen tension corresponding to about half the atmospheric value. The possible significance of the serological and bacteriological findings is discussed.