[2 cases of severe Streptococcus group A infection]. / Två fall av allvarlig grupp A-streptokockinfektion.

During recent years there have been several cases of death due to severe infection caused by GAS. Here we report two cases treated at our hospital, one of a patient presenting with preshock (case 1), the other of a patient with septic shock (case 2), in both of whom the concentrations of various coagulation factors and platelet counts were low. Other clinical findings common to both cases were scarlet coloured maculopapular exanthema, relative bradycardia, excessive tendency to develop oedema, and impaired function both in the lungs, kidneys and brain; and both patients were devoid of antibodies against the most predominant toxins (B and C) of the GAS strains isolated. Initial treatment comprised extensive administration of fluids, antibiotics, antithrombin, and low dose hydrocortisone. Plasma exchange by continuous centrifugation (CS 3000 Travenol Baxter) was given twice in case 1 and five times in case 2. In case 2, besides human immunoglobulin with a high anti-GAS (toxins A, B and C) antibody content given at admission, the patient received respiratory support, infusion of inotropic drugs and CAVH. Both patients recovered. The risk of death is high in cases of progressive multiple organ failure during the course of septic shock; and where conventional treatment combinations fail to remedy the condition, adjuvant treatment components may prove successful.

Use of serology to diagnose pneumonia caused by nonencapsulated Haemophilus influenzae and Moraxella catarrhalis.

Antibodies against nonencapsulated Haemophilus influenzae and Moraxella (Branhamella) catarrhalis were measured by ELISA in paired sera from 158 adult patients with pneumonia. A mixture of 10 clinical isolates of each species was used as antigen. Eleven patients (7%) showed significant increases in antibody to H. influenzae. In 3 of them, the organism was isolated from transtracheal aspirate and in another 7 from sputum, nasopharynx, or both. Six patients with nonencapsulated H. influenzae in transtracheal aspirate cultures did not show any antibody increase. Six patients had significant increases in antibody to M. catarrhalis. The organism was isolated in transtracheal aspirates from 1 of them and in sputum and nasopharynx (or both) from another 3. Two patients with M. catarrhalis in transtracheal aspirate cultures showed no antibody response. In conclusion, the serologic methods increased the possibility to diagnose infections caused by the two agents but had low sensitivity.

High prevalence of hypophosphataemia amongst patients with infectious diseases. A retrospective study.

OBJECTIVES: To describe the prevalence of hypophosphataemia amongst all patients treated during 1993 for infectious diseases. The associations between serum C-reactive protein, serum albumin and white blood cells in blood were studied amongst hypophosphataemic patients. Comparisons were made according to the severity of infection. DESIGN: A retrospective study of the prevalence of hypophosphataemia, and a case-control study amongst a subgroup of patients. SETTING: The Department of Infectious Diseases, University Hospital, Umeå, Sweden. SUBJECTS: For the prevalence study all 967 patients (449 women and 518 men) treated during 1993 were included. In the case-control study, 108 cases, with serum phosphate < or =0.64 mmol L(-1), 216 age-and sex-matched controls with serum phosphate >0.82 mmol L(-1) (men) and >0.86 mmol L(-1) (women), respectively, were included. RESULTS: In 402 of 967 patients (42%) at least one serum phosphate value was below the reference level. Hypophosphataemia was found in 573 of 1966 blood samples (29%). Severe hypophosphataemia (<0.30 mmol L(-1)) was seen in 1.2% of the patients (0.9% of blood samples). The prevalence of hypophosphataemia was higher amongst women than amongst men. In the case-control study, the serum C-reactive protein and the number of white blood cells was higher amongst the cases compared with the controls (124 vs. 94 mg L(-1) and 11.4 vs. 9.3 cells/L x10(9), respectively). The multiple logistic regression showed a 4-fold higher risk of having low serum phosphate in patients with severe infection, compared with mild infections. None of the other variables (albumin, days of hospital stay or white blood cells in blood) increased the risk for hypophosphataemia. CONCLUSIONS: The high prevalence of low serum phosphate levels and the increased risk of having low levels in severe infections shown in this study needs further attention.

Invasive pneumococcal infections: incidence, predisposing factors, and prognosis.

A retrospective analysis of the case records of 494 patients with 508 episodes of pneumococcal infections verified by cultures from blood or from cerebrospinal, pleural, and/or synovial fluid from 1964 through 1980 is presented and discussed in relation to the literature on invasive pneumococcal infections. The documented incidence (1976-1980) of pneumococcal meningitis in a defined area of southwestern Sweden was similar to that reported from the United States; 1.4 cases per 100,000 persons per year; for nonmeningitic infections (mainly bacteremic pneumonia) the incidence was 6.1 per 100,000 per year. The highest age-specific incidence was seen in infants younger than two years. In the vast majority of patients, predisposing conditions (young or old age or severe underlying diseases) were present. In adults, alcoholism was the most important risk factor. The fatality rate was 33% for patients with meningitis and 15% for patients with non-meningitic infections, figures that were strikingly similar to those reported in other studies. Underlying diseases and young or old age contributed significantly to the high mortality rates.

Candida albicans pneumonia.

The increased incidence of deep fungus infections, especially of the lungs, should be kept in mind. Although no characteristic pulmonary abnormality is found in candidiasis, the appearance is usually different from that seen in virus pneumonia, bronchopneumonia, or tuberculosis. The diagnosis is more difficult than in these conditions but the clinical and radiologic findings, together with cultures and serologic tests, often justify a provisional diagnosis which is sufficiently quick and reliable for the initiation of adequate treatment.

Clinical experience with azlocillin in the treatment of urinary tract infections with Pseudomonas aeruginosa.

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.

A comparative study of meningoencephalitis epidemics caused by echovirus type 7 and coxsackievirus type B5. Clinical and virological observations during two epidemics in northern Sweden.

Two epidemics of meningoencephalitis caused by echovirus type 7 and coxsackievirus type B 5 in the summer and autumn of 1973 in Umeå in Northern Sweden were compared. Most patients with echovirus 7 meningoencephalitis were neck stiff and 50% had a polymorphonuclear pleocytosis in the cerebrospinal fluid (CSF). The illness was usually mild. It appears to be the first time that an epidemic caused by this virus is described from Scandinavia. On the other hand most patients with coxsackievirus B 5 meningoencephalitis showed a more profound involvement of the central nervous system, with abnormal electroencephalograms in 70% and a long convalescence period. The number of cells in CSF was normal in 70% of these patients.

Pharmacokinetics of meropenem and its metabolite ICI 213,689 in healthy subjects with known renal metabolism of imipenem.

Six healthy male subjects who had received imipenem without cilastatin in previous studies, were given 500 mg meropenem as single 30 min intravenous infusions. Plasma and urine samples were collected for 12 h and meropenem and its metabolite were assayed by HPLC and RIA, respectively. The mean plasma half-life of meropenem was 0.8 h, mean plasma clearance 277 ml/min and the mean volume of distribution 20.4 l. The metabolite reached mean peak plasma concentrations of 1.5 mg/l. Renal clearance of meropenem averaged 200 ml/min. The mean urinary recovery of the metabolite was 20% and of unchanged drug 72% of the dose given. The recovery of meropenem ranged from 62.2% to 78.2% and was correlated to the urinary recovery of imipenem when given without cilastatin to the same subjects in previous studies (range 15.2-32.2%, rank correlation coefficient = 0.934). The results indicate that meropenem is much less susceptible to renal metabolism than imipenem. The inter-subject variability observed with meropenem correlates with the extent of urinary recovery of imipenem observed in previous studies with imipenem alone, indicating some susceptibility of meropenem to renal dehydropeptidase-I.

Serotype distribution of Streptococcus pneumoniae strains isolated from blood and cerebrospinal fluid in Sweden.

215 strains of Streptococcus pneumoniae isolated from blood or cerebrospinal fluid at 3 different laboratories in Sweden were serotyped by coagglutination and subtyped by the capsular reaction test. 78% of the strains belonged to serotypes which are included in or completely cross-immunogenic with serotypes included in the 14-valent vaccine while serotypes included in the 23-valent vaccine covered 89% of the isolates. Types 7F, 14 and 33F, which cannot be detected by counterimmunoelectrophoresis constituted 19% of all strains.

Long-term persistence of false positive antibody reactivity in HIV western blot testing of sera from a healthy blood donor.

HIV-Western blot (WB) testing of sequential sera from a blood donor revealed identical bands in the p24 and p55 positions. Additional testing using indirect immunofluorescence antibody technique, radioimmunoprecipitation assay and an HIV p24 antigen immunoassay were negative. During a 5-year follow-up period the blood donor has remained apparently healthy and no signs of disease have developed. We conclude that sera from this blood donor show a false positive HIV WB reactivity. The nature of this reactivity remains obscure but has practical implications for the routine HIV screening of blood donors.

A Swedish fatal case of nephropathia epidemica.

A previously healthy 55-year-old man with nephropathia epidemica (NE) developed disseminated intravascular coagulation, anuria and shock and died on day 6 of his disease. By use of indirect immunofluorescence technique and ELISA, specific serum IgM antibodies against Puumala virus could be detected, thus confirming the clinical diagnosis. This case demonstrates that NE in Scandinavia is a potentially lethal disease.

Cefuroxime treatment of urethritis caused by a beta-lactamase-producing strain of Neisseria gonorrhoeae.

A patient who contracted urethritis from a beta-lactamase-producing strain of Neisseria gonorrhoeae was successfully treated with the cephalosporin derivative cefuroxime. As expected, neither cefuroxime nor cefamandole was hydrolysed by plasmid-coded gonococcal beta-lactamase. Cefuroxime ought to be a valuable and efficacious substitute for penicillins in the treatment of gonhorrhoea due to beta-lactamase-producing gonococcal strains.

Efficacy and safety of cefpirome (HR810).

Sixty adult patients with suspected systemic bacterial infections were treated with cefpirome 1 g or 2 g twice daily for 5-22 days. Forty-seven patients were evaluable for clinical efficacy. Diagnoses in evaluable patients were urinary tract infections (20), pneumonia (10), soft tissue infections (17), and bone and joint infections (4); four patients had two infections each. Nine patients were bacteraemic and all were cured; the responsible bacteria were Escherichia coli (6), Streptococcus pneumoniae (1), Pseudomonas aeruginosa (1), and Haemophilus influenzae (1). One patient with a soft tissue infection failed to respond clinically to cefpirome. Bacteriologically, 41 of 48 isolated pathogens (85%) were eradicated. In wound cultures, three strains of Staphylococcus aureus and one each of Ps. aeruginosa and Str. faecalis persisted. One Enterobacter sp. relapsed in urine. Of isolated strains, only Str. faecalis and methicillin resistant Staph, epidermidis were resistant to cefpirome. Staph, aureus strains were inhibited in vitro by 0.25 to 2 mg/l of cefpirome in agar dilution. Adverse effects, probably or possibly related to cefpirome, were skin reactions (3), fever (1), Clostridium difficile diarrhoea (2), and disturbed taste sensation (1). Tolerance was good. Cefpirome is suitable for large-scale comparative trials.

Pharmacokinetics in healthy subjects of FCE 22101 and its acetoxymethyl ester, FCE 22891: effect of co-administration of imipenem/cilastatin on the renal metabolism of FCE 22101.

The pharmacokinetics of FCE 22101 were studied in eight healthy male subjects who received FCE 22101 intravenously alone or together with imipenem/cilastatin which was given to inhibit dehydropeptidase-I, a renal enzyme metabolizing penem and carbapenem antibiotics. The kinetics of FCE 22101 were also studied following oral administration of its acetoxymethyl ester, FCE 22891. For comparative purposes, the kinetics of imipenem and cilastatin, given alone or together with FCE 22101, were calculated. Intravenously administered FCE 22101 at a dose of 250 mg gave peak plasma concentrations of about 12 mg/l and the plasma half-life was about 60 min. Co-administration of FCE 22101 with imipenem/cilastatin did not affect the plasma kinetics of FCE 22101, nor did FCE 22101 influence the kinetics of imipenem or cilastatin. Cilastatin increased the urinary recovery of FCE 22101 from 17.5% to 53.0% with FCE 22101 alone to 73.2% to 91.8% when it was given with cilastatin. There was a high correlation between the urinary recovery of FCE 22101 in this study and that of imipenem given alone to the same subjects in previous studies; subjects who were high metabolizers of imipenem were also high metabolizers of FCE 22101. When FCE 22891 was given orally at a dose of 500 mg (corresponding to 400 mg of FCE 22101 free acid), peak concentrations of 2.2 to 6.1 mg/l were found. The absorption was rapid with peak concentrations achieved 20 to 80 min after administration. In comparison with imipenem, FCE 22101 seems to undergo less non-renal metabolism.

Diagnosis of pneumonia by cultures, bacterial and viral antigen detection tests, and serology with special reference to antibodies against pneumococcal antigens.

In a prospective study of the etiology of pneumonia 196 adult patients were included. One of the following criteria was required for diagnosis of pneumococcal pneumonia: isolation of pneumococci from blood; isolation from transtracheal aspirate; isolation from sputum or nasopharynx or detection of capsular antigen in sputum in combination with a significant increase in antibodies against at least one pneumococcal antigen (type-specific capsular polysaccharide, C-polysaccharide, pneumolysin); or increase in antibodies against two pneumococcal antigens. Pneumococcal pneumonia was diagnosed in 63 patients (32%). Other diagnoses were nonencapsulated Haemophilus influenzae isolated from transtracheal aspirates, 9; Mycoplasma pneumoniae diagnosed by serology, 17; Chlamydia psittaci, 6; and viral infections, 42. Twenty-two patients (11%) had evidence of infection with more than one agent. The pathogen could not be determined in 70 (36%). Many patients were given antibiotics before admittance to the study, and in some cases a convalescent serum sample was not available.

Randomised trial of 23-valent pneumococcal capsular polysaccharide vaccine in prevention of pneumonia in middle-aged and elderly people. Swedish Pneumococcal Vaccination Study Group.

BACKGROUND: We assessed the effectiveness of a 23-valent pneumococcal vaccine in the prevention of pneumococcal pneumonia and of pneumonia overall in non-immunocompromised middle-aged and elderly people. METHODS: The prospective, multicentre, double-blind, randomised, placebo-controlled trial was carried out across departments of infectious diseases at six tertiary-care or university hospitals in Sweden. 691 non-immunocompromised patients aged 50-85 years who had been treated as inpatients for community-acquired pneumonia (CAP) were randomly assigned either 23-valent pneumococcal capsular polysaccharide vaccine or placebo (sodium chloride). We used Cox regression models to estimate the relative risks of pneumonia overall and pneumococcal pneumonia for the placebo group compared with the vaccine group. FINDINGS: 63 (19%) of 339 patients in the vaccine group and 57 (16%) of 352 patients in the placebo group developed a new pneumonia, corresponding to a relative risk over time for the placebo group compared with the vaccine group of 0.83 (95% CI 0.58-1.12, p=0.31). Pneumococcal pneumonia was diagnosed in 16 (4.5%) patients in the placebo group and in 19 (5.6%) in the vaccine group, corresponding to a relative risk for the placebo group of 0.78 (95% CI 0.40-1.51, p=0.45). We found no difference in the death rate between the two study groups. INTERPRETATION: The 23-valent pneumococcal polysaccharide vaccine did not prevent pneumonia overall or pneumococcal pneumonia in middle-aged and elderly individuals.

Imipenem/cilastatin versus amikacin plus piperacillin in the treatment of infections in neutropenic patients: a prospective, randomized multi-clinic study.

In this open, controlled, randomized multi-clinic trial, monotherapy with imipenem/cilastatin was compared to amikacin plus piperacillin as empiric antibacterial therapy in 210 neutropenic cancer patients. Of patients randomized, 53 (25%) had bacteriologically documented infections and of those 30 had septicemia. A further 80 patients (38%) were evaluable for clinical efficacy but did not have documented infections. Seventy-seven patients (37%) were non-evaluable due to effective antibiotic treatment before the trial, early institution of other antibiotics during the trial, verified non-bacterial infections, no neutropenia or other reasons. There were no significant differences in terms of efficacy between imipenem/cilastatin and amikacin plus piperacillin but a consistent trend towards higher rates of clinical cure or improvement and of elimination of causative pathogens was noted in the imipenem/cilastatin group. In patients who were severely neutropenic (less than 0.1 x 10(9) granulocytes/l), similar cure rates were obtained in the two treatment groups--again with a tendency towards better results in the imipenem/cilastatin group. Among evaluable patients with septicemia, one patient in the imipenem/cilastatin group had persistent Staphylococcus aureus bacteremia during treatment. Five patients in the amikacin plus piperacillin group had persistent bacteremia during treatment; all but one (a Pseudomonas aeruginosa) caused by strains resistant to amikacin or piperacillin. Clinical and laboratory adverse effects were mild in the imipenem/cilastatin group although nausea was significantly more common than in the amikacin plus piperacillin group. Among patients on amikacin plus piperacillin, one died in renal failure, possibly related to treatment. Drug-related serious adverse events were reported in two additional amikacin plus piperacillin patients; one with drug fever and one with hearing loss. Microbiological adverse effects occurred in similar frequencies in the two groups. It is concluded that imipenem/cilastatin is a promising candidate for monotherapy of bacterial infections in neutropenic cancer patients.