Rainer Gattringer

Antibiotic Abscess Penetration: Fosfomycin Levels Measured in Pus and Simulated Concentration-Time Profiles

ABSTRACT The present study was performed to evaluate the ability of fosfomycin, a broad-spectrum antibiotic, to penetrate into abscess fluid. Twelve patients scheduled for surgical or computer tomography-guided abscess drainage received a single intravenous dose of 8 g of fosfomycin. The fosfomycin concentrations in plasma over time and in pus upon drainage were determined. A pharmacokinetic model was developed to estimate the concentration-time profile of fosfomycin in pus. Individual fosfomycin concentrations in abscess fluid at drainage varied substantially, ranging from below the limit of detection up to 168 mg/liter. The fosfomycin concentrations in pus of the study population correlated neither with plasma levels nor with the individual ratios of abscess surface area to volume. This finding was attributed to highly variable abscess permeability. The average concentration in pus was calculated to be 182 ± 64 mg/liter at steady state, exceeding the MIC50/90s of several bacterial species which are commonly involved in abscess formation, such as streptococci, staphylococci, and Escherichia coli. Hereby, the exceptionally long mean half-life of fosfomycin of 32 ± 39 h in abscess fluid may favor its antimicrobial effect because fosfomycin exerts time-dependent killing. After an initial loading dose of 10 to 12 g, fosfomycin should be administered at doses of 8 g three times per day to reach sufficient concentrations in abscess fluid and plasma. Applying this dosing regimen, fosfomycin levels in abscess fluid are expected to be effective after multiple doses in most patients.

Reduced valve replacement surgery and complication rate in Staphylococcus aureus endocarditis patients receiving acetyl-salicylic acid

OBJECTIVES To assess the influence of acetyl-salicylic acid (ASA) on clinical outcomes in Staphylococcus aureus infective endocarditis (SA-IE). METHODS The International Collaboration on Endocarditis - Prospective Cohort Study database was used in this observational study. Multivariable analysis of the SA-IE cohort compared outcomes in patients with and without ASA use, adjusting for other predictive variables, including: age, diabetes, hemodialysis, cancer, pacemaker, intracardiac defibrillator and methicillin resistance. RESULTS Data were analysed from 670 patients, 132 of whom were taking ASA at the time of SA-IE diagnosis. On multivariable analysis, ASA usage was associated with a significantly decreased overall rate of acute valve replacement surgery (OR 0.58 [95% CI 0.35-0.97]; p<0.04), particularly where valvular regurgitation, congestive heart failure or periannular abscess was the indication for such surgery (OR 0.46 [0.25-0.86]; p<0.02). There was no reduction in the overall rates of clinically apparent embolism with prior ASA usage, and no increase in hemorrhagic strokes in ASA-treated patients. CONCLUSIONS In this multinational prospective observational cohort, recent ASA usage was associated with a reduced occurrence of acute valve replacement surgery in SA-IE patients. Future investigations should focus on ASAs prophylactic and therapeutic use in high-risk and newly diagnosed patients with SA bacteremia and SA-IE, respectively.

Pharmacokinetics of Telithromycin in Plasma and Soft Tissues after Single-Dose Administration to Healthy Volunteers

ABSTRACT By use of microdialysis we assessed the concentrations of telithromycin in muscle and adipose tissue to test its ability to penetrate soft tissues. The ratios of the area under the concentration-versus-time curve from 0 to 24 h to the MIC indicated that free concentrations of telithromycin in tissue and plasma might be effective against Streptococcus pyogenes but not against staphylococci and human and animal bite pathogens.

Antibody responses to pneumococcal and hemophilus vaccinations in splenectomized patients with hematological malignancies or trauma

ZusammenfassungZiel der vorliegenden Studie war es zu untersuchen, ob eine zu Grunde liegende maligne hämatologische Erkrankung bei splenektomierten Patienten Einfluss auf die Immunantwort nach Impfung mit einem Bakterienpolysaccharid-Antigene (Streptococcus pneumoniae, Haemophilus influenzae) hat. Zwischen 1993 und 2003 wurden 44 splenektomierte Erwachsene in diese prospektive Studie eingeschlossen. 23 Patienten litten an einer malignen hämatologischen Erkrankung und waren zusätzlich splenektomiert (HM); 21 Patienten waren aufgrund eines Traumas splenektomiert (T) und dienten als Kontrollgruppe. Jeder Patient erhielt eine einmalige intramuskuläre Impfung mit 0,5 ml eines 23-valenten Pneumokokken Polysaccharid-Impfstoffes, sowie am anderen Arm 0,5 ml eines an Tetanus Toxid konjugierten Haemophilus influenzae Typ b Kapselpolysaccharid Impfstoffes. Betreffend die Impfantwort auf den 23-valenten Pneumokokken Impfstoff fand sich ein signifikant geringerer IgG und IgM Titeranstieg in der HM Gruppe verglichen mit der T-Gruppe (medianer IgG Anstieg: 1.27 [25 to 75% interquartile range: 0.7; 2.39] vs. 3.9 [2.1; 15.3] p < 0.001; medianer IgM Anstieg: 1.33 [1.0; 2.67] vs. 5.25 [2.33; 7.78], p < 0.001). In der HM Gruppe zeigten 8/23 und 6/23 Patienten einen zumindest zweifachen Titeranstieg von IgG und IgM, während die entsprechenden Werte für die T-Gruppe 16/21 und 16/20 betrugen. Der Antikörperanstieg in der HM Gruppe nach Hib-Impfung war zwar etwas ausgeprägter als nach der Pneumokokken-Polysaccharid Impfung, aber signifikant geringer als in der T-Gruppe. Zusammenfassend kann diskutiert werden, dass bei splenektomierten Patienten mit hämatologischer Grunderkrankung der Impferfolg nach Pneumokokken- aber auch nach Haemophilus influenzae-Impfung durch Bestimmung der Antikörper evaluiert werden sollte.SummaryIn this study we addressed the question of whether an underlying hematological malignancy may affect the immune response to vaccination against bacterial polysaccharide antigens (e.g. Haemophilus influenzae type b, Streptococcus pneumoniae) in splenectomized patients. Between 1993 and 2003, 44 splenectomized adults from the outpatient clinic for infectious diseases were prospectively included in the study: 23 patients suffered from hematological malignancies (HM) and had undergone splenectomy; 21 were splenectomized following trauma (T) and served as the control group. Each patient received an intradeltoid injection with 0.5 ml of a single lot of a 23-valent pneumococcal polysaccharide vaccine, and 0.5 ml of a polyribosyl ribitol phosphate capsular polysaccharide vaccine of H. influenzae type b (Hib) into the opposite arm. Blood samples for determination of pneumococcal and Hib antibodies were taken prior to vaccination and again 6–8 weeks later. In assessing responses to the 23-valent pneumococcal polysaccharide vaccine, we found significant differences in antibody titer increase between the HM and T groups (median IgG increase 1.27 [0.7; 2.39] vs. 3.9 [2.1; 15.3], P < 0.001; and median IgM increase 1.33 [1.0;2.67] vs. 5.25 [2.3; 7.78], P < 0.001). In the HM group, only 8/23 and 6/23 showed a titer increase of twice or more the base value for IgG and IgM respectively, whereas in the trauma group an adequate response was shown by 16/21 and 16/20 respectively. Patients with splenectomy and hematological malignancies responded poorly to the 23-valent polysaccharide vaccine. Response to the conjugated Hib vaccine was slightly better, but still significantly lower than in individuals with posttraumatic splenectomy. Data suggest that vaccination response to the polysaccharide vaccines should be evaluated at least in the high-risk group.