Determination of an inoculum effect with various cephalosporins among clinical isolates of methicillin-susceptible Staphylococcus aureus.

Using 98 clinical methicillin-susceptible Staphylococcus aureus isolates of known beta-lactamase (Bla) type, we found a pronounced inoculum effect for cephalexin (mostly Bla type A and C strains), a mild inoculum effect for cephalothin (especially types B and C), and no inoculum effects for ceftriaxone and cefuroxime. Ceftobiprole showed the lowest MICs at a high inoculum but with a slight increase for Bla-positive versus Bla-negative strains. Since a potential therapeutic effect associated with a cephalosporin inoculum effect has been described, further studies are warranted.

Inoculum effect with cefazolin among clinical isolates of methicillin-susceptible Staphylococcus aureus: frequency and possible cause of cefazolin treatment failure.

Methicillin (meticillin)-susceptible Staphylococcus aureus (MSSA) strains producing large amounts of type A beta-lactamase (Bla) have been associated with cefazolin failures, but the frequency and impact of these strains have not been well studied. Here we examined 98 MSSA clinical isolates and found that 26% produced type A Bla, 15% type B, 46% type C, and none type D and that 13% lacked blaZ. The cefazolin MIC(90) was 2 microg/ml for a standard inoculum and 32 microg/ml for a high inoculum, with 19% of isolates displaying a pronounced inoculum effect (MICs of >or=16 microg/ml with 10(7) CFU/ml) (9 type A and 10 type C Bla producers). At the high inoculum, type A producers displayed higher cefazolin MICs than type B or C producers, while type B and C producers displayed higher cefamandole MICs. Among isolates from hemodialysis patients with MSSA bacteremia, three from the six patients who experienced cefazolin failure showed a cefazolin inoculum effect, while none from the six patients successfully treated with cefazolin showed an inoculum effect, suggesting an association between these strains and cefazolin failure (P = 0.09 by Fisher's exact test). In summary, 19% of MSSA clinical isolates showed a pronounced inoculum effect with cefazolin, a phenomenon that could explain the cases of cefazolin failure previously reported for hemodialysis patients with MSSA bacteremia. These results suggest that for serious MSSA infections, the presence of a significant inoculum effect with cefazolin could be associated with clinical failure in patients treated with this cephalosporin, particularly when it is used at low doses.

Requirements for Staphylococcus aureus in vitro cellular internalization

Staphylcoccus aureus is a prokaryotic organism capable of causing numerous superficial and severe human infections. Adhesion of S. aureus to host tissues or cells is believed to be a crucial event in S. aureus infections. Subsequently, S. aureus can seed into the bloodstream resulting in metastasis of the infection. Several reports show that S. aureus can be internalized by non-professional phagocytes, a process which has been proposed to be important in S. aureus dissemination. An intracellular residence has also been proposed to provide safe harbor to reservoirs of dormant bacteria contributing to the persistence of infection. This dissertation describes an investigation into the molecular mechanisms of S. aureus internalization into both fibroblast and epithelial cells. Bacterial requirements for internalization were found to be limited to expression of proteins that bind the extracellular matrix protein fibronectin. A previously unknown fibronectin-binding region in the S. aureus fibronectin-binding protein A was discovered after showing competitive inhibition of S. aureus internalization. This novel fibronectin-binding activity is characterized. Internalization also required cell-based factors. The presence of fibronectin and cell surface receptors of the β1 integrin class, which are known to bind and internalize fibronectin, were found to be necessary for optimal internalization of S. aureus. These results led to the conclusion that fibronectin acts as a bridge between the bacterium and integrins on the host cells. The internalization process exhibits features characteristic of integrin-mediated cell migration on fibronectin-coated surfaces. Both processes involved an active form of the β1 integrin subunit and the protein tyrosine kinase Src. Finally, a Src inhibitor previously shown to be effective in reducing osteoporosis in an in vivo rat model is capable of greatly reducing S. aureus internalization. ^

Comparative Disciplinary Rates as a Tool for Reducing Exclusionary Discipline and Eliminating the School to Prison Pipeline

Invited Commentary on "Comparing Campus Discipline Rates: A Multivariate Approach for Identifying Schools with Significantly Different than Expected Exclusionary Discipline Rates" by Eric Booth and colleagues.

William Osler: Original Papers 1881-1897

Part 1: 1881-1888 On Some Points in the Etiology and Pathology of Ulcerative Endocarditis, 1881 On Certain Parasites in the Blood of the Frog, 1883 The Third Corpuscle of the Blood, 1883 On the Use of Arsenic in Certain Forms of Anaemia, 1886 Antifebrin, 1887 Case of Arterio-Venous Aneurism of the Axillary Artery and Vein of Fourteen Year's Duration, 1887 Typhilitis and Appendicitis, 1888 Part 2: 1889-1892 Annual Address - License to Practice 1889 Case of Syphiloma of the Cord of the Cauda Equina-Death From Diffuse Central Myelitis, 1889 On a Case of Simple Idiopathic Muscular Atrophy, Involving the Face and the Scapulo-Humeral Muscles, 1889 Note on Intra-Thoracic Growths Developing from the Thyroid Gland, 1889 On the Value of Laveran's Organisms in the Diagnosis of Malaria, 1889 On the Form of Convulsive Tic Associated with Corprolalia, Etc., 1890 A Case of Sensory Aphasia Word-blindness with Hemianopsia, 1891 Rudolf Virchow: The Man and the Student, 1891 The Healing of Tuberculosis, 1892 The Cold-Bath Treatment of Typhoid Fever, 1892 Part 3: 1893 Remarks on the Varieties of Chronic Chorea, and a Report Upon Two Families of the Hereditary Form, With One Autopsy, 1893 Note on Arsenical Neuritis Following the use of Fowler's Solution, 1893 Note on a Remarkable House Epidemic of Typhoid Fever, 1893 Cases of Sub-Phrenic Abscess, 1893 On Sporadic Cretinism in America, 1893 Notes on Tuberculosis in Children, 1893 Part 4: 1849-1895 Parotitis in Pneumonia, Case of Pericarditis Treated by Incision and Drainage, 1894 The Army Surgeon, 1894 Introductory Remarks to Course of Clinical Demonstrations on Typhoid Fever, 1894 Cancer of the Stomach with Very Rapid Course, 1895 Case of Sporadic Cretinism (Infantile Myxcedema) Treated Successfully with Thyroid Extract, 1895 Visible Contractile Tumour of the Pylorus Following Ulcer of the Stomach, 1895 On the Association of Enormous Heart Hypertrophy, Chronic Proliferative Peritonitis, and Recurring Ascites, with Adherent Pericardium, 1895 Teaching and Thinking the Two Functions of a Medical School, 1895 The Practical Value of Laveran's Discoveries, 1895 Part 5 1896 Addison's Disease, 1896 On Six Cases of Addison's Disease, 1896 Hemiplegia in Typhoid Fever Thomas Dover (of Dover's Powder) Physician and Buccaneer, 1896 John Keats The Apothecary Poet, 1896 On The Classification of the Tics or Habit Movements, 1896 The Cerebral Complication of Raynaud's Disease, 1896 Part 6: 1897 On Certain Features in the Prognosis of Pneumonia, 1897 Clinical Lecture on Mitral Stenosis - Sudden Death - Ball Thrombus in the Left Auricle, 1897 The Diagnosis of Malarial Fever, 1897 The Functions of a State Faculty (President's Address), 1897 A Clinical Lecture on The Ball-Valve Gall-Stone in the Common Duct, 1897 Pneumonia (Review of Cases studied), 1897 Internal Medicine as a Vocation, 1897 Back Notes