Staphylococcus aureus secretes numerous exotoxins which may exhibit superantigenic properties. Whereas the virulence of several of them is well documented, their exact biological effects are not ...fully understood. Exotoxins may influence the immune and inflammatory state of various organs, including the sinonasal mucosa: their possible involvement in chronic rhinosinusitis has been suggested and is one of the main trends in current research. The aim of this study was to investigate whether the presence of any of the 22 currently known staphylococcal exotoxin genes could be correlated with chronic rhinosinusitis.
We conducted a prospective, multi-centred European study, analysing 93 Staphylococcus aureus positive swabs taken from the middle meatus of patients suffering from chronic rhinosinusitis, with or without nasal polyposis, and controls. Strains were systematically tested for the presence of the 22 currently known exotoxin genes and genotyped according to their agr groups. No direct correlation was observed between chronic rhinosinusitis, with or without nasal polyposis, and either agr groups or the presence of the most studied exotoxins genes (egc, sea, seb, pvl, exfoliatins or tsst-1). However, genes for enterotoxins P and Q were frequently observed in nasal polyposis for the first time, but absent in the control group. The number of exotoxin genes detected was not statistically different among the 3 patient groups.
Unlike many previous studies have been suggesting, we did not find any evident correlation between staphylococcal exotoxin genes and the presence or severity of chronic rhinosinusitis with or without nasal polyposis.
Severe infections due to Staphylococcus aureus require prolonged therapy for cure, and relapse may occur even years after the first episode. Persistence of S. aureus may be explained, in part, by ...nasal carriage of S. aureus which occurs in a large percentage of healthy humans and represents a major source of systemic infection. However, the persistence of internalized S. aureus within mucosal cells has not been evaluated in humans. Here, we provide the first in vivo evidence of intracellular reservoirs of S. aureus in humans, which were assessed in endonasal mucosa specimens from patients suffering from recurrent S. aureus rhinosinusitis due to unique, patient-specific bacterial clonotypes. Heavily infected foci of intracellular bacteria located in nasal epithelium, glandular, and myofibroblastic cells were revealed by inverted confocal laser scan fluorescence and electron microscopic examination of posttherapy intranasal biopsy specimens from symptom-free patients undergoing surgery on the sinuses. Intracellular residence may provide a sanctuary for pathogenic bacteria by protecting them from host defense mechanisms and antibiotic treatment during acute, recurrent S. aureus rhinosinusitis
Abstract Small-colony variants (SCVs) of Staphylococcus aureus are phenotypic variants characterised by their small colony size and improved intracellular survival and are associated with persistent ...and relapsing infections. XF drugs are membrane-active, porphyrin-based antibacterial agents for topical administration, exerting rapid bactericidal activity against actively growing or resting, antibiotic-susceptible and multidrug-resistant strains of S. aureus . In this study, minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of XF-70 against isogenic, electron-transport deficient, SCV hemB mutants of one meticillin-susceptible S. aureus (MSSA) strain and one meticillin-resistant S. aureus (MRSA) strain were evaluated. Macrodilution MICs of XF-70 for MSSA strain 8325-4 and its hemB+ -complemented derivative (0.5–1 mg/L) were reproducible and were slightly higher than that for the SCV hemB mutant (0.25–0.5 mg/L) and were not influenced by increasing inoculum size from 106 to 108 colony-forming units (CFU)/mL. MICs for MRSA strain COL, its SCV hemB mutant and hemB+ -complemented derivative were equivalent (0.25–1 mg/L). MBCs of XF-70 were ≤2-fold higher than MICs for all isolates. Extensive killing (≥4 log reduction in CFU/mL) was produced by 2 mg/L XF-70 within 30 min against SCV hemB mutants both of 8325-4 and COL as well as their respective parent or hemB+ -complemented derivatives. Pre-incubation of 107 CFU/mL of 8325-4 and its SCV hemB mutant with 5 × 106 polymorphonuclear neutrophils for 30 min markedly protected phagocytised organisms from rapid extensive killing by bactericidal levels (2 mg/L) of subsequently added XF-70. The rapid bactericidal activity of XF-70 at low concentrations both against SCV and normally growing S. aureus is remarkable and represents an attractive potential for the treatment of persistent localised infections.
Background
Increased antibiotic resistance against
Staphylococcus aureus
and low penetration into bone requires regimen optimization of available drugs.
Methods
We evaluate pharmoacokinetic and ...pharmacodynamic parameters (PK/PD) as well as
in vivo
interactions of continuous flucloxacillin 12 g/d administration combined with high dose oral rifampicin 600 mg bid in the serum of 15 adult patients with bone and soft tissue infections. We use the patient’s own serum directed against his own isolated
S. aureus
strain to reproduce
in vivo
conditions as closely as possible.
Results
The continuous flucloxacillin infusion constantly generated plasma free drug levels largely exceeding the serum minimal inhibitory concentrations (mean 74-fold). Combination with rifampicin significantly increased flucloxacillin levels by 44.5%. Such an increase following rifampicin introduction was documented in 10/15 patients, whereas a decrease was observed in 1/15 patients. Finally, all infections were cured and the combination was well tolerated.
Conclusions
In this
in vivo
methodological pilot study among adult patients with orthopaedic infections due to
S. aureus
, we describe a new method and reveal substantial but inconsistent interactions between flucloxacillin and rifampicin, of which the clinical significance remains unclear.
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