Outbreak of nosocomial infections with two different MRSA-strains involved: significance of genomic DNA fragment patterns in strains otherwise difficult to type.

Methicillin-resistant Staphylococcus aureus isolates from an outbreak of 17 cases of wound infection in a municipal hospital were typed by conventional methods, phage typing by three sets of phages, reverse phage typing and plasmid profiles, as well as by genomic DNA fragment patterns obtained after Sma-I digestion and pulsed-field electrophoresis. These isolates were non-typable by phages, only some were typable by reverse phage typing and were not uniform in plasmid profile. Only the genomic DNA fragment patterns resulted in a clear discrimination of 2 strains (12 isolates for the first and 7 isolates for the second). Both strains were disseminated in different wards of the same hospital and one strain had obviously spread to another clinic in the same city.

[A rare cause of infection in chronic dialysis patients: Malta fever (febris undulans melitensis)]. / Seltene Sepsisursache bei chronischem Dialysepatienten: Maltafieber (Febris undulans melitensis).

A 45-years-old Greek patient developed septicaemia in his 10th year of hemodialysis treatment. Clinical investigation was directed first on bacterial infection of the arteriovenous shunt, on urosepsis or bronchopulmonary infection. Then, serologically (Widal's reaction and ELISA-test) and in different blood-cultures Brucella melitensis was detected as causative agent for Malta fever (Febris undulans). The focus of infection is suspected in unpasteurized sheep-milk cheese of mediterranean origine, wherein Brucella species can survive for months. The patient was treated effectively by a combination of amoxycilline and clavulanic acid.

Penetration of eight beta-lactam antibiotics into the peritoneal fluid. A pharmacokinetic investigation.

Serial serum and peritoneal fluid samples were taken after intravenous injection of cefuroxime sodium, cefoxitin sodium, cefotaxime sodium, cefoperazone sodium, ceftazidime, moxalactam disodium, mezlocillin sodium, and piperacillin sodium. Time-concentration curves were obtained for both pharmacokinetic compartments. The geometric mean of peritoneal fluid concentrations from eight to ten patients was used to define the time-concentrations curve for each substance. Serum pharmacokinetic values were calculated using an open two-compartment model. The concentrations (Cps) were calculated from peritoneal fluid concentrations by quadratic interpolation. The time for which one fourth of the Cp (Cp1/4) is maintained within the peritoneal cavity varied according to the substance and can be used to estimate dosage intervals. The Cp1/4 was compared with the minimal inhibitory concentrations for 1,344 pathogens encountered in 415 intra-abdominal infections from 31 studies.

[Use of hydroxyapatite for determination of antibiotic concentrations in bone]. / Uber die Bedeutung des Hydroxilapatits bei Konzentrations-bestimmungen von Antibiotika im Knochen.

A new method to determine antibiotic bone concentrations is presented. The bone fragments, obtained during hip joint replacement operations in 10 patients were investigated for antibiotic activity after i.v. application of 2 g of oxacillin and 4 g of mezlocillin. We were able to show that both penicillins do not penetrate into the inorganic bone part (hydroxylapatite). Therefore the concentrations measured are related to the organic bone part and are expressed in units per volume rather than in units per weight. With this method the differences between spongious and cancellous bone observed so far are diminished to values without any statistical difference. After 2 g of oxacillin and 4 g of mezlocillin the concentrations are 13.1 mg/l and 34.0 mg/l, respectively. The serum concentrations measured are compared to the bone concentrations. The terminal serum half-life is 63 min for oxacillin and 80 min for mezlocillin when the drugs are given simultaneously.

Distribution of moxalactam in serum, bone, tissue fluid, and peritoneal fluid.

Concentration-vs.-time curves in serum, peritoneal fluid, bone, and tissue fluid were determined after 2-g intravenous doses of moxalactam. Serum concentrations were measured in five volunteers (group 1; mean age, 22.8 years). Serum and peritoneal fluid concentrations were measured in eight patients (group 2; mean age, 66.5 years). Serum, bone, and tissue fluid concentrations were measured in eight patients (group 3; mean age, 71.5 years). The serum concentrations fitted an open two-compartment model. In groups 1, 2, and 3, the respective serum beta-phase half lives were 134, 169, and 184 min. In group 2, the peak concentration in peritoneal fluid was 43.8 mg/liter after 2.02 hr, with one-quarter of this concentration being maintained for 13 hr. In group 3, the bone concentrations were 19.4 mg/liter after 60 min and 19.1 mg/liter after 120 min; the peak concentration in tissue fluid was 36.1 mg/liter after 2.4 hr, with one-quarter of this concentration being maintained for 15 hr. These concentrations in tissues will inhibit most aerobic and anaerobic bacteria that cause infections.

[Pharmacokinetic investigations on the penetration of mezlocillin into the pleural fluid]. / Pharmakokinetische Untersuchungen über die Penetration von Mezlocillin in das Pleurasekret.

5 g of mezlocillin were administered by a 30 minute drip infusion to each of ten patients (mean age 59.4 years). Antibiotic concentrations in serum and pleural fluid were assayed microbiologically at regular intervals. The antibiotic concentrations determined 1.5 and 8 hours after beginning the infusion were between 83.9 and 4.0 mg/l in the serum and 53.1 and 6.5 mg/l in the pleural fluid. A comparison of the mean antibiotic concentration found in the pleural secretions (22 mg/l) with the minimal inhibitory concentrations of clinically relevant pathogens shows that mezlocillin covers 69% to 84% of the pathogen spectrum. Mezlocillin can thus be used in the therapy of infectious pleural effusions.

[Antibiotic concentrations in the abdominal cavity as basis for antibacterial therapy of peritonitis: penetration of mezlocillin into the peritoneal exudate]. / Antibiotikakonzentrationen in der Bauchhöhle als Grundlage der antibakteriellen Peritonitistherapie: Zur Frage der Penetration von Mezlocillin in das Peritonealexsudat.

The importance of the antibiotic concentration in peritoneal exudate is emphasized as a criterium for the possible success of antibiotic therapy of intra-abdominal infections. 5 g of mezlocillin were given i. v. over 15 min to ten patients with a mean age of 56 years. The serum concentrations, assayed microbiologically, were: 299.5 mg/l at the end of the infusion, 103.2 mg/l, 18.6 mg/l and 2.1 mg/l 60, 240 and 480 min after the end of the infusion, respectively. The serum half-life T1/2 beta, calculated from the beta phase, was 67 min. In the peritoneal fluid the peak concentration of Cp = 42.0 mg/l was achieved after 2.2 h. A quarter of this concentration was maintained in the peritoneal cavity for five to six hours. This concentration inhibited 74% of the 322 pathogens isolated from 123 intra-abdominal infections.

[Studies with azlocillin, mezlocillin, penicillin-g-potassium and sisomicin on tolerance in the cornea and the kinetics of inhibiting concentrations in the cornea and aqueous humor in rabbits]. / Untersuchungen zur Verträglichkeit an der Cornea und zur Kinetik von Hemmstoffkonzentrationen in Hornhaut und Kammerwasser des Kaninchens mit den Antibiotika Azlocillin, Mezlocillin, Penicillin G-Kalium und Sisomicin.

We studied the effect of azlocillin, mezlocillin and sisomicin in concentrations of 1, 2.5 and 5% on the regeneration of stromal corneal wounds in rabbits following subconjunctival injections and treatment with eye drops. Concentrations of the antibiotics were also determined in corneal tissue and in aqueous humor and compared with that of penicillin G-potassium. Together with azlocillin, sisomicin proved to be the most effective and the safest. Mezlocillin only inhibited wound regeneration slightly and thus mezlocillin appears to be inferior to the other two antibiotics investigated in the local treatment of the eye.

[The penetration of moxalactam into bone (author's transl)]. / Zur Frage der Penetration von Moxalactam in den Knochen.

After injection of 2 g of moxalactam over 5 minutes in 8 patients with mean age of 71,5 years, serum halflife was found to be T 50% beta = 184 min and the volume of distribution at steady state VDSS = 17,45l, whereas these figures in volunteers with mean age of 22.8 years were T 50% beta = 134 min and VDSS 16,80l respectively. The concentrations in organic bone were 30 to 60 min after injection of 2 g of Moxalactam 19,40 mg/l with a deviation factor of 1,43 and 61 to 120 min after injection 19,08 mg/l with a deviation factor of 1,16. The problems of penetration of antibiotics into bone are discussed. Moxalactam does not penetrate into anorganic bone (hydroxylapatite).

[Pharmacokinetic studies on the penetration of azlocillin and mezlocillin into bone and tissue fluid (author's transl)]. / Pharmakokinetische Untersuchungen zur Penetration von Azlocillin und Mezlocillin in den Knochen und in die Gewebsflüssigkeit.

During and after hip replacement arthroplasty antimicrobial concentrations in serum, bone and tissue-fluid were determined microbiologically using agar diffusion assay technique after 15-min infusion of 5 g 6-[D-2-(2-oxoimidazolidine-1-carboxamido)-2-phenylacetamido] - penicillanic acid (azlocillin) and 5 g 6-[D-2-(3-methylsulfonyl-2-oxoimidazolin-1-ylcarboxamido)-2-phenylacetamido]-penicillanic acid (mezlocillin) and after i.v. bolus injection of 2 g mezlocillin. Serum pharmacokinetic data on the individual patients are computer derived using a modified open two-compartment model. The geometric mean of bone level determinations at defined intervals with deviation factor are presented. These results are related to the organic bone compartment and are expressed in mg/l. From the tissue fluid-concentration curve, peak concentration CP and its time were calculated. The time for which one-fourth of the peak concentration CP 1/4 was maintained in tissue fluid was determined graphically. This concentration is compared with the cumulative minimum inhibitory concentrations of representative bacteria causing bone and joint infections. These results are focused as criteria of valuation of antimicrobial chemotherapy.

Activity of ceftazidime and newer antibiotics against Gram-negative bacilli.

Ceftazidime is a new parenterally applicable cephalosporin with high beta-lactamase stability and a remarkable activity against the Enterobacteriaceae and non-fermentative Gram-negative bacilli. The in-vitro activity of ceftazidime in general is comparable with that of cefotaxime and moxalactam. Ceftazidime proved the most active of the newer cephalosporins against Ps. aeruginosa, Ps. cepacia, Ser. marcescens and Pr. vulgaris. The bactericidal effectiveness of ceftazidime is excellent against the majority of species tested. Ceftazidime is a promising new beta-lactam antibiotic and the first clinical results seem to confirm the excellent in-vitro activity.

Pharmacokinetic studies of ceftazidime in serum, bone, bile, tissue fluid and peritoneal fluid.

After a single iv bolus injection of 2 g ceftazidime, concentrations were measured in serum and urine in volunteers and in serum, bone, bile and tissue fluid in patients. The serum half-life was 171 min in volunteers (n=6, average age 26 years) and 221 min in patients (n=12, average age 58 years). The peripheral volumes of distribution were also different, being 7.81 in volunteers and 11.31 in patients. Urinary recovery from the volunteers averaged 92% of the dose. Bone samples free from blood and taken from the femoral head, the pelvis or the femoral shaft contained an average of 24.1 mg ceftazidime per litre of organic bone at 30 min after injection and 19.7 mg/l at 2 h. Samples of fluid from the periprosthetic space after hip replacement contained 25.6 mg/l at 2 h and were above 8 mg/l at 10 h. Bile concentrations reached 36.4 mg/l at 90 min and were above 8 mg/l for over 8 h. Peritoneal fluid samples contained 27.6 mg/l at 1 h and 8.0 mg/l at 8 h. These concentrations are considered sufficient to treat most aerobic infections associated with surgery.

[Availability of cefotaxime. Pharmacokinetic studies on the distribution in central and various peripheral compartments (author's transl)]. / Verfügbarkeit von Cefotaxim. Pharmakokinestische Untersuchungen über die Verteilung in zentralen und verschiedenen peripheren Kompartimenten.

After 2 g as a bolus injection the concentration of Cefotaxime was determined in serum, bone, tissue fluid, peritoneal exudate and bile under clinical conditions in 43 patients with a mean age of 61 years. Pharmacokinetic constants were calculated using a modified two compartment model. The basis for these calculations was a mean serum curve from 299 serum samples. The geometric mean and deviation factors of time-dependent values in tissue and tissue fluid are presented. The results are compared to the minimal inhibitory concentrations of pathogenic bacteria. The clinical success in 121 severe infections at a dose of 2 g every 12 hours support the theoretical results of this study.

[Fosfomycin, a new antibiotic: in vitro activity compared with mezlocillin, cefuroxime and gentamicin]. / Fosfomycin, ein neues Antibiotikum: In-vitro-aktivität im Vergleich mit Mezlocillin, Cefuroxim und Gentamicin.

In vitro investigations with fosfomycin, mezlocillin, cefuroxime, and gentamicin against staphylococci, enterobacteriaceae an pseudomonadaceae were carried out by Agar Dilution method on Mueller-Hinton agar. The fosfomycin breakpoint for the low dosage of 2-3 times 3 g per infusion daily was defined with 16 micro g/ml and for the high dosage of 2-3 times 5 g fosfomycin per infusion with 64 micro g/ml. At a concentration of 16 micro g/l fosfomycin more than 90% of the cultures of staph. aureus (penicillin-resistant), e. coli, proteus mirabilis an proteus vulgaris examined were inhibited. At a concentration of less than 64 micro g/ml fosfomycin 80 toi 100% of the cultures of serratia marcescens, klebsiella pneumoniae, enterobacter cloacae, proteus morgani et rettgeri and pseudomonas aeruginosa (gentamicin sensitive and resistant) were inhibited. Fosfomycin showed an absolute stability against many Beta-Lactamases of different bacterial species.

[Bacteriology of the stomach after operation (author's transl)]. / Bakteriologie des operierten Magens.

The intergastric bacterial flora was studied in 125 patients after different types of ulcer operations and correlated with pH value and histological state of gastric mucosa. Following vagotomy most of the gastric juices were sterile whereas more than 60% of the resected stomach were contaminated with fecal and oropharyngeal flora. After jejunal transposition the proportion of fecal flora was reduced to one-third. There was a good correlation between bacterial overgrowth and pH value. Only 10-20% of the stomachs with pH values lower than 4.5 and more than 80% of the stomachs with pH values above 6 were bacterially contaminated. Intragastric flora was found in 90% of the stomachs with atrophic gastritis. The synergistic role of intragastric bacterial flora in carcinogenesis by deconjugation of the bile acids and production of nitrosamine is emphasized.

[Postoperative heart infection caused by M. fortuitum (author's transl)]. / Postoperative Herzinfektion mit M. fortuitum.

Shortly after an open-heart operation a 5-year-old girl died of an infection caused by M. fortuitum. Strains of this species are often isolated from human specimens, but generally they are not correlated with pulmonary tuberculosis. Nevertheless M. fortuitum produces relatively often infections after transplantations of different kind. The diagnosis is difficult to find, especially because nobody thinks of the possibility that a rapid growing mycobacterium is able to cause such infections. -- The therapy is very problematical. That is why these infections are not seldom fatal.

[Dibekacin--a novel aminoglycoside antibioticl. Antimicrobial activity and parallel resistance in vitro]. / Dibekacin--ein neues Aminoglykosid-Antibiotikum. Antimikrobielle Aktivität und Parallelresistenzen in vitro.

Dibekacin (Orbicin) is a new aminoglycoside antibiotic which chemically differs from tobramycin only by lack of an OH-group. The activity of dibekacin against E. coli, Klebsiella, Enterobacter, Serratia, Proteus indol-negative and indol-positive and Pseudomonas aeruginosa was compared with that of gentamicin, sisomicin, tobramycin and amikacin by tube dilution procedure. Dibekacin showed a high activity against P. aeruginosa including gentamicin-resistant strains. The development of resistance and cross-resistance in vitro in E. coli, Klebsiella, Proteus and P. aeruginosa to the five aminoglycosides was investigated. The experimentally produced resistance under increasing aminoglycoside concentrations was developing by multiple-step mutation. The frequency of cross-resistance is of great importance for the first choice of an aminoglycoside antibiotic in the hospitals. These in vitro studies have yielded that dibekacin and gentamicin are well suited for the first choice of an aminoglycoside in P. aeruginosa infection.