Sydney M. Finegold

Sydney "Sid" Martin Finegold (August 21, 1921 – September 17, 2018) was an American physician, medical school professor, and researcher in infectious diseases caused by anaerobic bacteria. He was elected in 1971 a Fellow of the American Academy for the Advancement of Science.

Quotes

 * Several classes of antimicrobial agents (e.g., penicillins, cephalosporins, tetracyclines, chloramphenicol, and clindamycin) are useful in treatment of infections due to anaerobic bacteria. However, certain anaerobic bacteria have shown a striking resistance to antimicrobial agents. In vitro susceptibility tests are useful for selection of optimal therapy. The choice of agent depends, to some extent, on the organisms responsible for the infection. Bacteroides fragilis is the most commonly encountered anaerobe, and it is also the most resistant to antimicrobial agents. Other factors influencing the selection of therapy include pharmacologic characteristics, degree of bactericidal activity, and toxicity. Proper therapy for anaerobic infections often requires intensive antimicrobial therapy for a prolonged period. Surgical intervention, including drainage of abscesses and excision of necrotic tissue, is important.


 * The bacteria typically described from biliary tract infection include Escherichia coli, Klebsiella, Enterobacter, and enterococci. It has also been recognized for some time that Clostridium perfringens may occasionally be involved in serious complications of biliary tract infection such as sepsis and emphysematous cholecystitis. Other anaerobes, including various Bacteroides and Fusobacterium sp, clostridia other than C perfringens, anaerobic cocci and streptococci, and Actinomyces have been reported from a variety of biliary tract infections, usually as single case reports ... More recently, several reports indicate that anaerobes, and especially B fragilis, may be more common in biliary tract infections than had been appreciated ... Anaerobes have been recovered in approximately 40% of such infections; B fragilis is the most common anaerobe encountered. Anaerobes may also be found, as aerobes are, in asymptomatic bactibilia.


 * Anaerobic bacteria produce many different enzymes that are of importance in providing nutrients to the bacterial cell, as virulence factors, and in permitting organisms to colonize or survive under adverse conditions (including exposure to antimicrobial agents). Some enzymes effect several types of modifications to bile acids, neutral steroids, and corticosteroids. Anaerobes are clearly important in a variety of infections in humans and animals as well as in various other types of pathologic processes.
 * 1979


 * There is an impressive incidence of anaerobes in major infections involving the lung and pleural space, intra-abdominal sites, and the female genital tract. Almost all anaerobic infections are endogenous in origin. Therapy consists of making the environment such that anaerobes find it difficult to proliferate, checking the spread of anaerobes into healthy tissues, and neutralizing the toxins of anaerobes.


 * Anaerobes are prevalent on all mucosal surfaces and virtually all anaerobic infections are endogenous. Two thirds of anaerobic infections involve five anaerobic organisms or groups—the Bacteroides fragilis group, the Bacteroides melaninogenicus-Bacteroides asaccharolyticus group, Fusobacterium nucleatum, the anaerobic cocci, and Clostridium perfringens. Conditions that lower the oxidation-reduction potential and disrupt the mucosal surface (eg, vascular problems, malignant neoplasms, and surgery) lead to infection with anaerobes. Clues to anaerobic infection include foul odor, gas, tissue destruction, underlying malignant neoplasms, and the unique appearance of certain anaerobes on Gram's stain. Specimens must be collected to avoid normal flora and transported to the laboratory under anaerobic conditions. Therapy involves surgical débridement and drainage and the use of various antimicrobial agents. Antimicrobial agents must be used for extended periods to avoid relapse.


 * The field of infectious diseases covers many entities that can be considered true medical emergencies. Included are meningitis, brain abscess, spinal epidural abscess, epiglottitis, pneumonia, bacteremia, endocarditis, certain intraabdominal infections, gas gangrene, and necrotizing fasciitis. Because emergencies related to infectious agents are potentially the most readily reversible of all medical emergencies, it behooves us to diagnose them as rapidly and specifically as possible so that appropriate life-saving therapy may be begun expeditiously.


 * The commonly used drugs that have a major effect on the colonic flora are ampicillin, cefoperazone, clindamycin and oral neomycin or kanamycin, used together with either tetracycline, erythromycin or metronidazole.


 * Most gastrointestinal infections secondary to the use of antimicrobial agents that have been documented are related to overgrowth of Clostridium difficile which produces a spectrum from severe pseudomembranous colitis to mild diarrhea or asymptomatic carriage. The most common inducers of pseudomembranous colitis or antimicrobial agent-associated diarrhea are ampicillin, clindamycin, and various cephalosporins, but almost all antimicrobials may cause this problem. Symptoms vary from watery to bloody diarrhea; the extent and severity of the diarrhea, fever, and abdominal cramps and the incidence of complications (such as toxic megacolon and perforation of the bowel) and of fatality are variable. Normal carriage of C. difficile in infants and asymptomatic carriage in adults who have received antimicrobial therapy make it impossible to rely on culture for diagnosis. The presence of cytotoxin or enterotoxin produced by C. difficile is much more reliable diagnostically, but there may be false-positives with this as well, particularly in infants.


 * Anaerobic bacteria currently demonstrate increased resistance to antimicrobial agents, primarily by the production of beta-lactamase. A number of species of Bacteroides, most notably those in the Bacteroides fragilis group, produce these enzymes. A few species of Fusobacterium and Clostridium produce beta-lactamase as well. Fortunately, this mechanism of resistance is readily overcome by administering beta-lactamase inhibitors coupled with a beta-lactam antibiotic that would otherwise be inactivated. Other types of resistance encountered in anaerobic bacteria include inactivating enzymes such as chloramphenicol acetyltransferase, plasmid-mediated transferable multiple-drug resistance, changes in porin molecules in the outer membrane of the bacterial cell, decreased uptake of drug by other mechanisms, changes in the target organs such as penicillin-binding proteins, and decreased reduction of the antibiotic to an active intermediate product. In many institutions, certain drugs such as cefoxitin, clindamycin, and piperacillin, which were previously active against almost all strains of B. fragilis, are now effective against only 70 to 85% of this group of anaerobes.


 * Much of the available data on the incidence of anaerobic infections is not reliable. Bacteriologic data without clinical correlation are not adequate, since the organisms are not necessarily significant. Similarly, clinical data with fragmentary bacteriological information are not ideal. In both types of papers, one often finds data on specimens cultured for anaerobes that clearly must have been contaminated with normal flora (for example, coughed sputum and voided urine). The exact specimen type and source is not always indicated or recognizable.


 * Anaerobic or mixed anaerobic-aerobic pulmonary infection is important both in community-acquired disease and in the hospital setting. Its principal causes are aspiration of oral or gastic contents and of organisms involved in periodontal disease. Indeed, pneumonia following aspiration is undoubtedly the most common type of hospital-acquired pneumonia and as such is a major cause of death and disability in hospitalized patients. Both endogenous oral flora (primarily anaerobes and viridans streptococci) and hospital-acquired oral or gastric flora (such as Staphylococcus aureus, various members of the Enterobacteriaceae family, and Pseudomonas) may be involved in the infections. The principal complications are tissue destruction (necrotizing pneumonia), abscess formation, and thoracic empyema.


 * ... (1) What is the clinical relevance of anaerobic bacteriology? (2) How can the microbiologist, with limited and decreasing resources, perform reliable, detailed studies of anaerobic bacteriology? (3) When and how should susceptibility testing be done with anaerobes? If the clinician knows the usual bacteriology of various types of infection and how this may be modified by pathophysiologic processes in the host or by prior therapy, he/she can use a logical empiric approach to treatment of the patient. As to the microbiologist's dilemma, it is not realistic or rational for a microbiologist in a nonteaching hospital to do detailed bacteriologic studies and routine anaerobic susceptibility testing. The resources available should be committed primarily to the patient who is seriously ill. Such allocation of resources, of course, requires repeated and effective communication between microbiologist and clinician.


 * It has been a hundred years since the role of anaerobic bacteria and, especially, non-spore-forming anaerobes in infections began to be appreciated.


 * The most clinically important anaerobes are the five genera of Gram-negative rods. Bacteroides, especially the B. fragilis group (made of up ten species, one of which is the species B. fragilis), is particularly important. The other Gram-negative genera are Prevotella, Porphyromonas, Fusobacterium, and Bilophila. Among the Gram-positive anaerobes, there are cocci (primarily Peptostreptococcus) and sporeforming (Clostridium) and non-sporeforming bacilli (especially Actinomyces and Propionibacterium).


 * ... a recent study of ours employing the powerful pyrosequencing technique on stools of subjects with regressive autism showed that Desulfovibrio was more common in autistic subjects than in controls. We subsequently confirmed this with pilot cultural and real-time PCR studies and found siblings of autistic children had counts of Desulfovibrio that were intermediate, suggesting possible spread of the organism in the family environment. Desulfovibrio is an anaerobic bacillus that does not produce spores but is nevertheless resistant to aerobic and other adverse conditions by other mechanisms and is commonly resistant to certain antimicrobial agents (such as cephalosporins) often used to treat ear and other infections that are relatively common in childhood. This bacterium also produces important virulence factors and its physiology and metabolism position it uniquely to account for much of the pathophysiology seen in autism.