Microindentation of cartilage before and after articular loading in a bioreactor: assessment of length-scale dependency using two analysis methods.

Background: Microindentation is a technique with high sensitivity and spatial resolution, allowing for measurements at small-scale indentation depths. Various methods of indentation analysis to determine output properties exist. Objective: Here, the Oliver-Pharr Method and Hertzian Method were compared for stiffness analyses of articular cartilage at varying length-scales before and after bioreactor loading. Methods: Using three different conospherical tips with varying radii (20, 100, 793.75 µm), a bioreactor-indenter workflow was performed on cartilage explants to assess changes in stiffness due to articular loading. For all data, both the Oliver-Pharr Method and Hertzian Method were applied for indentation analysis. Results: The reduced moduli calculated by the Hertzian Method were found to be similar to those of the Oliver-Pharr Method when the 20 µm tip size was used. The reduced moduli calculated using the Hertzian Method were found to be consistent across the varying length-scales, whereas for the Oliver-Pharr Method, adhesion/suction led to the largest tip exhibiting an increased average reduced modulus compared to the two smaller tips. Loading induced stiffening of articular cartilage was observed consistently, regardless of tip size or indentation analysis applied. Conclusions: Overall, geometric linearity is preserved across all tip sizes for the Hertzian Method and may be assumed for the two smaller tip sizes using the Oliver-Pharr Method. These findings further validate the previously described stiffening response of the superficial zone of cartilage after articular loading and demonstrate that the finding is length-scale independent.

Bacteremia associated with decubitus ulcers.

We studied 104 episodes of bacteremia in 102 patients with decubitus ulcers observed over five years in the hospitals of one metropolitan area. The ulcers were considered to be the "probable" source of bacteremia in 49% of episodes. Another site of infection was documented in 86% of patients. Proteus mirabilis, Staphylococcus aureus, and Escherichia coli were the most frequent blood isolates in these patients, but only Bacteroides species correlated with "probable" origin of bacteremia from the ulcers. The overall mortality was 55%, with 51% of deaths being attributed to infection. These findings emphasize the importance of decubitus ulcers as potential sources of bacteremia in hospitalized patients.

Bacteremia in diabetic patients: comparison of incidence and mortality with nondiabetic patients.

We determined the incidence of bacteremia and associated mortality in diabetic and nondiabetic patients in the four major hospitals of one metropolitan area over the 5-yr period 1977-1981. Mortality rates, based on episodes of bacteremia, were similar in diabetic and nondiabetic patients in most instances. Diabetic patients experienced lower mortality rates from Enterobacteriaceae bacteremia compared with nondiabetic patients; this finding was explained by a greater tendency for diabetic patients to have Escherichia coli bacteremia due to community-acquired urinary tract infection. However, the incidence of bacteremia due to all microorganisms was increased twofold in diabetic patients and the incidence of Enterobacteriaceae bacteremia was increased threefold. Because of their increased incidence of bacteremia, diabetic patients in this population were nearly twice as likely to die as a result of bacteremia compared with nondiabetic patients. Thus, the frequent occurrence of bacteremia among patients with diabetes mellitus represents a significant problem.

Carbenicillin therapy in patients with normal and impaired renal function.

Optimun therapy with carbenicillin entails the use of high serum concentrations and the risk of significant dose-related toxicity. We report a study of serum clearance method of dose adjustment of carbenicillin patients with normal and imparied renal function. This method was found to provide serum concentrations considered to be satisfactory in every instance, by either constant-rate or intermittent infusion, and should enable greater precision in the use of the antibiotic. Implications of these findings aimed at providing dosage schedules for patients with renal failure are discussed.

Treatment of pneumococcal pneumonia: the case for penicillin G.

Although widely endorsed for specific treatment of pneumococcal pneumonia, penicillin G is seldom used for this purpose in clinical practice for at least three reasons: (1) concern about penicillin-resistant Streptococcus pneumoniae (PRSP) strains; (2) the difficulty of making an early etiologic diagnosis of pneumonia; and (3) lack of a clear consensus about the optimum dosage. Continuous infusion of 20-24 million units of penicillin per day provides serum levels of 16-20 microg/mL in persons with normal renal function. These levels easily exceed the minimum inhibitory concentrations (MICs) of penicillin G against most PRSP strains (4 microg/mL), which are actually strains with reduced susceptibility to penicillin. High-dose penicillin G therapy has not been shown to be therapeutically ineffective against pneumonia due to PRSP strains. However, the extent of penicillin resistance warrants continued monitoring, because strains exhibiting extremely high-level resistance (MIC > or = 8 microg/mL) would probably respond poorly if at all. Development and use of rapid, sensitive, specific ways to diagnose pneumococcal pneumonia could extend the usefulness of penicillin G, thus postponing the emergence of resistance to other antibiotics.

Gram-negative bacillary endocarditis. Interpretation of the serum bactericial test.

Although the serum bactericidal test is commonly used in the management of infective endocarditis, little has been written about its validity or limitations. We report three cases of gram-negative bacillary endocarditis (Pseudomonas aeruginosa, Vibrio fetus and Serratia marcescens) encountered in 1 year at a Veterans Administration hospital. Serum bactericidal titers were considered necessary to identify inadequate antibiotic regimens or to avoid unnecessary drug toxicity. The limitations of the test, particularly those pertaining to gram-negative infections, are reviewed. Misleading results during treatment with aminoglycoside antibiotics could be due to the tendency of serum to become alkaline on standing. A detailed study of the interaction of the complement-dependent bactericidal system of serum with eight antibiotics is presented. In the context of the serum bactericidal test, the interaction was additive or synergistic in 15 of 16 determinations, indicating the need to include a control study of serum sensitivity of the infecting microorganism in each case.

Penicillin dosing for pneumococcal pneumonia.

Most textbook authors still endorse penicillin G as the specific antibiotic of choice for pneumococcal pneumonia. However, problems with early precise etiologic diagnosis of pneumonia and the emergence of drug-resistant pneumococci cause penicillin to be seldom used for this purpose today. A third explanation for the infrequent use of penicillin is lack of clear consensus dosing guidelines. Emergence of pneumococci resistant to the newer cephalosporins and concerns about overuse of vancomycin, however, have prompted renewed interest in the development of precise, rapid methods for diagnosis of pneumococcal pneumonia with the implication that penicillin might be used more frequently. We review several issues concerning penicillin dosing: intermittent vs continuous therapy, high dose vs low dose, relationship of dose to resistance, and cost-effective pharmacology. An optimum "high-dose" regimen for life-threatening pneumococcal pneumonia in a 70-kg adult consists of a 3 million unit (mu) loading dose followed by continuous infusion of 10 to 12 mu of freshly prepared drug every 12 h. The maintenance dose should be reduced in elderly patients and in patients with renal failure according to the following formula: dose (mu/24 h = 4+[creatinine clearance divided by 7]). This regimen provides a penicillin serum level of 16 to 20 microg/mL, which should suffice for all but the most highly resistant strains (minimum inhibitory concentration > or = 4 microg/mL). Newer cephalosporins and vancomycin can be reserved for patients with suspected meningitis or endocarditis or for localities in which highly resistant pneumococci are known to be prevalent.

Endocarditis related to transvenous pacemakers. Syndromes and surgical implications.

Two cases of microbial endocarditis related to transvenous pacemakers illustrate syndromes whose pathogenesis we consider to be distinctive. Acute Pseudomonas aeruginosa endocarditis related to a pacemaker developed in a 75-year-old man, an event which to our knowledge has not been previously described. There was no evidence of generator site infection, and the sequence of events indicated metastatic implantation of bacteria on traumatized endothelium. A 76-year-old women with a 3 year history of local generator site infection and recurrent fever was found to have extensive vegatative Staphylococcus epidermidis endocarditis at cardiotomy. The sequence of events indicated gradual spread of infection locally, related to the contaminated foreign body. Awareness of these separate pathogenetic mechanisms should facilitate recognition and appropriate management. Removal of the entire pacing system and prolonged antibiotic therapy were considered to be essential to cure of infection in both instances.

Comparison of cefamandole and cefazolin during cardiopulmonary bypass.

In a randomized comparison, concentrations of cefazolin were found to exceed those of cefamandole in serum, atrial appendage, and sternal bone in patients undergoing cardiopulmonary bypass. No postoperative infections and no antibiotic-related complications occurred in either patient group.

Utility of the hospital tuberculosis registry.

Emerging guidelines suggest that the management of tuberculosis and suspected tuberculosis in the hospital will become an increasingly costly enterprise. The local hospital registry can be a focal point for determining the extent to which such measures are necessary at individual institutions, that existing infection control recommendations are being carried out, and that patients released from the hospital are not lost to follow-up. Consideration might be given to inclusion of all patients begun on antituberculous therapy, regardless of the results of acid-fast bacilli cultures, in view of renewed concern about patient compliance.

Changing patterns of mycobacterial disease at a teaching community hospital.

OBJECTIVES: To evaluate trends in the occurrence and diagnosis of mycobacterial disease. DESIGN: Prospective surveillance study using a central tuberculosis registry at a 611-bed teaching community hospital. RESULTS: Data pertaining to 715 patients were entered into the registry between 1976 and 1991 on the basis of positive smears or cultures for acid-fast bacilli (AFB). Over time, the ratio of isolates of Mycobacterium tuberculosis to isolates of nontuberculous mycobacteria reversed (from 3.2 to 1 between 1976 and 1981 to 1 to 1.6 between 1986 and 1991). The sensitivity of the sputum AFB smear for diagnosis of pulmonary tuberculosis increased (from 0.73 to 0.96), but the positive predictive value of the sputum AFB smear declined (from 0.72 to 0.59). The acquired immunodeficiency syndrome epidemic accounted for these changes only to a small extent. CONCLUSIONS: The increasing occurrence of non-tuberculous mycobacterial disease and the declining positive predictive value of the sputum AFB smear at this hospital imply that respiratory isolation and antituberculous therapy will be used inappropriately for many patients. The development and use of newer tests for early isolation and specific identification of M tuberculosis should be accelerated.

Petriellidium boydii infection of the sphenoid sinus.

Petriellidium boydii infection of the sphenoid sinus in a previously healthy woman was initially diagnosed by immunofluorescent staining of biopsy tissue sections. The diagnosis was confirmed by demonstrating P. boydii precipitins in serum and by isolating the infecting fungus. Despite surgical drainage and intensive therapy with miconazole nitrate, the outcome, because of intracranial extension, was fatal.

The hospital tuberculosis registry: an aid to infection control.

Maintenance of a "central tuberculosis registry" has been proposed to facilitate communication between hospital personnel and other persons such as members of health departments and practicing physicians involved in the care of patients. A 5-year experience revealed additional benefits: (1) recognition, and partial correction, of deficiencies in tuberculin testing; (2) recognition and termination of a pseudoepidemic of false positive acid-fast bacilli smears; (3) increased frequency with which patients were placed in respiratory isolation at the time of admission to the hospital; and (4) decrease in the indicence of tuberculin conversions among hospital employees. It is suggested that such a registry should be included in all hospital infection control programs.

Implementing control measures.

Implementation is the means by which a favorable infection control policy leads to a favorable result (low infection rate). Determination of endemic infection rates by traditional surveillance (outcome surveillance) may, in many situations, be a relatively insensitive method for identifying suboptimal implementation practices. Surveillance of the practices themselves (process surveillance) may identify situations likely to lead to unfavorable results and thus provide early feedback to personnel. Innovative approaches to process surveillance are needed in order to enhance motivation.

Postpartum cytomegalovirus infection. A hazard of multiple transfusions.

A patient whose postpartum course included the defibrination syndrome and Bacteroides septicemia developed recurrent high fever. Cytomegalovirus infection was suspected on the basis of the clinical features and a history of massive blood transfusion, and was confirmed by subsequent observations. Recognition of this disease and its typically benign course averts the need for extensive diagnostic procedures, exploration, and empiric drug therapy trials.

Bacteremia in obstetrics and gynecology.

Surveillance of all episodes of bacteremia in the four major hospitals of a metropolitan area of 400,000 population between 1977 and 1981 revealed that bacteremia was documented in only 92 patients on obstetrics and gynecology services. Death was attributed to bacteremia in only four of these patients, three of whom had severe underlying diseases. These data confirm that death due to bacteremia in present-day obstetric and gynecology practice is extremely uncommon.

Strategies to improve antibiotic use.

The desideratum of "appropriate" antibiotic therapy include efficacy, safety, and low cost. Strategies for achieving these goals include education, control of the hospital formulary, written justification forms and automatic stop orders, ongoing utilization review, restriction, required consultation, control of laboratory susceptibility testing, and limitation of contact time between physicians and pharmaceutical representatives. Because traditional education methods have had limited impact on "appropriate" antibiotic use, the potential of the newer strategies must be explored. Most published studies emanate from teaching hospitals, leaving the applicability of the findings to community hospitals largely unsettled. At each hospital, it should be determined which combination of strategies will strike the best balance between effectiveness and palatability. Computer technology continues to hold promise as a way to provide instantaneous, nonthreatening feedback to prescribing physicians.

Bacteroides bacteremia. Analysis of 142 episodes from one metropolitan area.

Overall mortality for 142 patients with Bacteroides bacteremia encountered in the four hospitals of one metropolitan area between 1977 and 1982 was 41%. Only 43% of deaths of these patients, however, were attributed directly to Bacteroides infection according to the criteria used in this study. Deaths of patients with Bacteroides bacteremia, compared with deaths of patients with bacteremia due to aerobic gram-negative rods, were less likely to occur early after onset of bacteremia. Choice of antimicrobial therapy had no obvious relationship to eventual outcome. Nonobstetrical Bacteroides bacteremia identifies a group of patients at high risk of death during hospitalization. The diversity of both clinical and microbiologic features of these infections, however, makes specific recommendations regarding optimum therapy difficult to formulate.

Vertebral osteomyelitis due to Staphylococcus warneri attributed to a Hickman catheter.

A patient with a long-term right atrial (Hickman) catheter developed vertebral osteomyelitis due to Staphylococcus warneri. Documentation of this event--to our knowledge previously unreported--was made possible by use of special studies including plasmid profiles of the coagulase-negative staphylococcal isolates.

Posttraumatic meningitis due to ampicillin-resistant Hemophilus influenzae. Case report.

Two men who sustained skull fractures secondary to blunt head trauma developed meningitis due to Hemophilus influenzae type b. The isolates in both cases were resistant to ampicillin but susceptible to chloramphenicol. Based of this experience, and recent epidemiological trends, it is suggested that chloramphenicol, rather than penicillin G, might be the initial therapy of choice for posttraumatic meningitis when no micro-organisms are recognized on Gram-stained smears of the cerebrospinal fluid.