Persistent bacteremia in staphylococcal endocarditis

Methicillin-tolerant staphylococci are organisms that are inhibited by low concentrations of the drug but are resistant to its bactericidal effects. The clinical significance of this in vitro phenomenon is unknown. An experimental model of staphylococcal endocarditis in rabbits was used to determine whether methicillin-tolerant staphylococci are particularly difficult to eradicate from infected heart valves. In vitro sensitivity testing was used to identify a tolerant and a nontolerant strain of Staphylococcus aureus . Rabbits prepared by the insertion of a polyethylene catheter into the left ventricle and injected with a tolerant strain survived significantly longer than those injected with a nontolerant strain. No significant differences were demonstrated in the prevention of endocarditis with a single prophylactic dose of methicillin, or in the treatment of established endocardial infection with multiple doses of methicillin. In this study, methicillin had the same activity against experimental endocarditis caused by a tolerant and a nontolerant strain of S. aureus .

Section: Methodssupporting

confidence: 93%

Significance of Methicillin Tolerance in Experimental Staphylococcal Endocarditis

Goldman

Petersdorf

1979

“…This patient remained bacteremic for 6 days and febrile for 27 days despite sequential therapy with teicoplanin, nafcillin, and, finally, vancomycin plus rifampin. A similarly protracted course has been well documented in many other patients treated with conventional antistaphylococcal antibiotics (5,10,15,18,23).…”

Section: Resultsmentioning

confidence: 68%

“…Because of persistent bacteremia, nafcillin was substituted for teicoplanin on hospital day 7. Subsequent blood cultures were sterile; however, the patient continued to have spiking fever and chills. On day 18 nafcillin was discontinued, and therapy was successfully completed with vancomycin and rifampin for an additional 25 days. Fever persisted until day 27 of treatment.…”

Section: Resultsmentioning

confidence: 99%

Clinical evaluation of efficacy, pharmacokinetics, and safety of teicoplanin for serious gram-positive infections

Bibler¹,

Frame²,

Hagler³

et al. 1987

Teicoplanin is a new glycopeptide antibiotic structurally related to vancomycin and ristocetin. Like vancomycin, it is highly active in vitro against a wide spectrum of grampositive organisms, including enterococci and both methicillin-susceptible and methicillin-resistant staphylococci (3,14,21). Unlike vancomycin, however, teicoplanin has a long elimination half-life permitting administration once a day (11,20,21), and it is well tolerated when given intramuscularly (i.m.), with a bioavailability of 90% (21)

“…This indicates that the improved killing of drug-damaged microorganisms by phagocytes occurred with Streptococcus pneumoniae but not with Staphylococcus aureus. This observation may explain why microorganisms persist during several days of adequate antimicrobial therapy in staphylococcal but not in pneumococcal infection (21).…”

mentioning

confidence: 97%

Pharmacokinetics and Pharmacodynamics of Levofloxacin againstStreptococcus pneumoniaeandStaphylococcus aureusin Human Skin Blister Fluid

Trampuž

Wenk

Rajacic

et al. 2000

The pharmacokinetics of levofloxacin in serum and in skin blister fluid (SBF) was determined for 20 volunteers after a single 500-mg oral dose of levofloxacin. In addition, ex vivo bactericidal activity of SBF against Streptococcus pneumoniae and Staphylococcus aureus was studied. SBF containing levofloxacin and granulocytes killed 5.2 log of Streptococcus pneumoniae bacteria and 2.0 log of Staphylococcus aureus bacteria during a 6-h incubation.Fluoroquinolones are rapidly acting and concentration-dependent bactericidal antibiotics that inhibit bacterial DNA gyrase (22). The earlier quinolones (e.g., norfloxacin and ciprofloxacin) are active mainly against gram-negative pathogens. The newer molecules retained their activity against gram-negative bacteria and exhibit improved activity against gram-positive bacteria and atypical pathogens, such as Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella pneumophila (1,5,6,16). Levofloxacin penetrates well into polymorphonuclear leukocytes (PMN), which can act as vehicles for transport and delivery of the active drug to sites of infection. Accumulation of the drug in PMN plays an important role in the treatment of intracellular pathogens (7,10,18).In order to establish the tissue penetration of the drug, we analyzed the respective pharmacokinetic parameters of levofloxacin in serum and in the inflammatory fluid of skin blisters. In addition, we studied the ex vivo bactericidal activity of skin blister fluid (SBF) against two common clinical pathogens, Streptococcus pneumoniae and Staphylococcus aureus. Skin cantharide blisters were provoked in human volunteers, and SBF was sampled before, and at regular intervals after, a single oral dose of levofloxacin (12). The inflammatory exudate was incubated ex vivo with a clinical isolate of Streptococcus pneumoniae (serotype 3) and a methicillin-susceptible laboratory strain of Staphylococcus aureus (ATCC 29213). Time-kill curves were obtained by inoculation of 3 ϫ 10 6 CFU/ml for studies with Streptococcus pneumoniae and by inoculation of 1.5 ϫ 10 6 CFU/ml for studies with Staphylococcus aureus. The MICs and minimal bactericidal concentrations (MBCs) of levofloxacin for both test strains were established by a standard macrodilution assay in Mueller-Hinton broth (Becton Dickinson), with a final inoculum of approximately 5 ϫ 10 5 CFU/ml, and incubated at 37°C for 24 h as described by the National Committee for Clinical Laboratory Standards (15). For in vitro testing, we used the commercially available levofloxacin (Tavanic) as an aqueous infusion solution (Hoechst Marion Roussel, Zurich, Switzerland). For the volunteer study, we used film-coated tablets (Tavanic) containing 512.46 mg of levofloxacin hemihydrate, corresponding to 500 mg of levofloxacin as an active ingredient (Hoechst Marion Roussel). Each volunteer received a single oral dose of 500 mg of this commercially available drug.Approval for this study was obtained from the Ethics Committee of the University Hospitals. Twenty healthy male and female volunteers p...