Darwin L. Palmer

Diagnostic and therapeutic considerations in Nocardia asteroides infection.

From the Departments of Medicine and Pathology, University of New- Mexico School of Medicine, and Veterans Administration Hospital, Albuquerque, New Mexico.

Alcoholism, infection and altered host defenses: A review of clinical and experimental observations

THE INFECTIOUS complications that follow alcohol abuse have been chronicled in the American medical literature since 1785 when Benjamin Rush published ‘An Inquiry into the Effects of Ardent Spirits Upon the Human Body and Mind’ [l]. Among the evils of drink, he described ‘hoarseness and husky cough, which often terminate in consumption, and sometimes in an acute and fatal disease of the lungs . . . . ‘. In reference to yellow fever, he noted ‘hard drinkers seldom escape, and rarely recover from them’. In current medical doctrine, acute alcohol excess, alcoholism, or the resulting liver disease is still considered a major predisposition to infection [2, 31 The world-wide prevalence of alcoholism remains high, and in the United States alone, it is estimated at 5-10 million individuals plus additional ‘problem’ and spree drinkers [4, 51. As a result, the question of increased susceptibility to infection is of considerable importance. To arrive at a satisfactory answer, three investigational approaches have been used. First, epidemiologic studies may be devised to detect an increased prevalence or incidence of infection in alcoholics as compared to a control, non-alcoholic population. Unfortunately, the epidemiologic or statistical foundation of most clinical studies of alcohol and infection has generally been weak or lacking. The mere enumeration of alcoholics present among patients with a specific infection has often been taken as sufficient evidence to establish a relationship. Clearly, for demonstration of an increase in attack rate among alcoholics, comparative figures of infection in non-alcoholics are needed. Preferably both groups should be studied prospectively after careful matching of subjects and controls. Moreover, one must distinguish clearly between incidence and prevalence [6] and must know these rates in both the alcoholic and non-alcoholic segments of the population. By definition, incidence refers to the number of cases of a disease which occur in a known community or population over a given period of time. In contrast, prevalence is defined as the number of cases of disease present in a given community at one moment in time. Both are calculated per unit of population potentially at risk.

Chronic Osteomyelitis caused by Staphylococcus Aureus: Controlled Clinical Trial of Nafcillin Therapy and Nafcillin-Rifampin Therapy

A controlled trial of treatment of chronic osteomyelitis caused by Staphylococcus aureus compared nafcillin alone with nafcillin plus rifampin for a six-week period. Treatment was well tolerated, the only adverse effect being mild neutropenia in four of 18 patients; no toxicity was observed from rifampin. Eight of ten patients in the combined treatment group had a favorable clinical response (with follow-up of two to four years) as compared to four of eight in the nafcillin group (P=.2). Despite the failure to show a statistically significant advantage of rifampin plus nafcillin, we conclude that the combination, along with appropriate surgery, should be considered for patients with chronic staphylococcal osteomyelitis.

Pneumonia treated with imipenem/cilastatin

In an open, prospective, multicenter trial the efficacy and tolerance of imipenem/cilastatin for the treatment of bacterial pneumonia was investigated. Forty-three adults were studied: 29 with nosocomial and 14 with community-acquired infections. Significant underlying disease was present in 91 percent of patients. Nosocomial infection was frequently associated with endotracheal intubation (48 percent), prior antibiotic therapy (48 percent), and recent surgery (31 percent). Most frequent sputum isolates included Pseudomonas aeruginosa (10, all nosocomial), Hemophilus influenzae (10), Escherichia coli (eight), Staphylococcus aureus (seven), and Streptococcus pneumoniae (six). Treatment with imipenem/cilastatin was associated with clinical cure in 93 percent of patients. Two of three failures and one superinfection occurred in association with isolates of Pseudomonas aeruginosa resistant to imipenem. Overall, six of 10 strains of Pseudomonas aeruginosa isolated prior to therapy developed resistance to imipenem after an average of 10 days of therapy. Adverse effects occurred in nine patients (21 percent) and included one case of pseudomembranous colitis. Monotherapy with imipenem/cilastatin of serious lower respiratory tract infections was relatively safe and highly effective with the exception of disease associated with P. aeruginosa.

Clinical applications of a new parenteral antibiotic in the treatment of severe bacterial infections

Cephalosporins are one of the mainstays of antibiotic therapy, and third-generation cephalosporins are first-line agents for the treatment of many types of serious infections, including those of nosocomial origin. Gaps in activity of currently available third-generation cephalosporins such as cefotaxime, cefoperazone, ceftriaxone, and ceftazidime, and increasing reports of gram-negative bacilli resistance to some of these agents, especially Klebsiella pneumoniae, Pseudomonas aeruginosa, and Enterobacter spp., make it necessary to investigate new compounds. Cefepime, a fourth-generation cephalosporin with a wide range of activity against gram-positive and gram-negative bacteria, including multi-resistant strains of Enterobacteriaceae, was evaluated in comparison with ceftazidime for the treatment of serious infections in hospitalized patients. Ceftazidime is a commonly prescribed third-generation cephalosporin used for empiric treatment of serious infections such as pneumonia, urinary tract infection, and skin and skin-structure infection. This investigation was an open, randomized comparative study involving 882 patients in North America. Cefepime 2 g every 12 hours demonstrated similar efficacy to that of ceftazidime 2 g every 8 hours for the treatment of pneumonia and urinary tract infection (including cases associated with concurrent bacteremia), and skin and skin-structure infections. The bacteriologic responses were generally >85%. The most common pathogens isolated were Escherichia coll, Streptococcus pneumoniae, P. aeruginosa, K. pneumoniae, Haemophilus influenzae, Staphylococcus aureus, and Streptococcus, group B. Overall, approximately 94% of pathogens isolated in pretreatment cultures were susceptible to cefepime and ceftazidime. Cefepime and ceftazidime were well tolerated; only 3% of patients in each group discontinued therapy because of an adverse event. The most common adverse events were headache, diarrhea, nausea, vomiting, pruritus, and rash. The results of this study indicate that cefepime is a promising, effective, and safe single-agent therapy for serious infections in hospitalized patients.

Anergy in patients with leukocytosis

Abstract To confirm and clarify a previously found association between anergy and leukocytosis, patients with leukocyte counts above 15,000/mm 3 were tested with five intradermal antigens, challenged with dinitrochlorobenzene (DNCB) and croton oil, and their lymphocytes studied in vitro. Of 32 patients with leukocytosis, 8 were unresponsive to all antigens; none of these 8 could be sensitized to DNCB, and only 3 had lymphocytes responsive to phytohemagglutinin. Only one was lymphopenic, and croton oil elicited weak or negative responses in five. Concurrent disease included pancreatitis, pneumonia, sepsis, urinary tract infection, abscess and endocarditis. Although quite ill, none had uremia, known malignancy or miliary tuberculosis, and none was taking immunosuppressive medications. Our evidence suggests that the anergy associated with leukocytosis may be an acute defect in lymphocyte function rather than a transient depression of the inflammatory response, and that leukocytosis may be a common clinically significant cause for depressed delay hypersensitivity in acutely ill patients.

Microbiology of pneumonia in the patient at risk

Microorganisms causing pulmonary infections in high risk patients vary considerably with the predisposing illness (immunosuppression, alcoholism, or diabetes), the setting (nosocomial or community-acquired), and previous therapy (antibiotics, surgery, and inhalation therapy). Even in the immunocompromised patient, conventional bacteria are the most prevalent opportunistic pathogens, and gram-positive cocci such as staphylococci and gram-negative bacilli such as Escherichia coli cause most pneumonias. Fungi, viruses, and protozoa also cause pulmonary infections, but they vary in frequency from one institution to another. Diagnostic proof of the etiology of pulmonary infection is often difficult to obtain. The microbial flora of sputum is not definitive and must be confirmed by blood or pleural fluid culture, antigen or serologic response in body fluids, or morphologic presence in lung tissue. Resistance to antimicrobial therapy is increasing, especially among nosocomially acquired gram-negative bacilli and methicillin-resistant staphylococci. A potential for increased resistance exists in pneumococcal, viral, and fungal infection but is not yet apparent in pulmonary infections due to protozoal pathogens. Tests to predict antibiotic response such as serum bactericidal assay, repeated cultures, and serologic studies are helpful but correlate imperfectly with clinical outcome.

Enterobacter Mediastinitis Following Cardiac Surgery

Eight cases of sternal/mediastinal infection due to Enterobacter species were seen in postoperative cardiac patients during 1980 to 1981. The attack rate was 14.5% (8/55), compared to 3.7% (2/54) for an identical period in 1979 to 1980 (p less than 0.05). Cases varied in severity from fulminant, acute bacteremic infections (one death) to less severe wound infection. Late complications or recurrences were not seen. There was a hospital-wide increase, relative to all other gram-negative bacillary isolates, in Enterobacter laboratory isolations, but no increased rate of infection in any other specific surgical condition. No personnel, materials, or techniques were associated with the outbreak, and all but two environmental cultures were negative. Case-control analysis suggested that surgical complications and prophylactic cephalosporins were associated with infection. Prospectively, an additional 85 cardiac surgery patients had increased Enterobacter skin/wound colonization following perioperative prophylaxis with cephalosporin antibiotics. After introduction of barrier isolation and restriction of contacts no further mediastinitis occurred in 100 subsequent cardiac surgery patients. This study indicates that Enterobacter may be major pathogens causing post-cardiac-surgery infection not prevented by cephalosporin prophylaxis.

Bacterial wound colonization after broad-spectrum versus narrow-spectrum antibiotics.

Broad-spectrum versus narrow-spectrum antibiotic prophylaxis for patients who undergo cardiac operations is variously advocated to reduce the incidence of all infections or, conversely, to prevent resistant superinfections. Previous studies of prophylaxis have shown a reduction in the incidence of staphylococcal infections with some increased resistance. We studied preoperative and postoperative wound colonization as a surrogate for infection. Among 78 patients undergoing cardiac procedures, the type of prophylaxis was allocated as follows: narrow-spectrum (nafcillin), 24 patients; midspectrum (cephapirin), 26 patients; and broad-spectrum (ceftriaxone), 28 patients. Seventeen patients who underwent other procedures received no antibiotics and served as controls. Cultures of the operative site were done preoperatively, and 3 and 6 days postoperatively. The incidence of preoperative skin colonization with staphylococci was identical (95%) in all groups. Postoperatively, more patients receiving nafcillin (48%) were culture-negative for all organisms than were either of the other groups receiving antibiotics (27% and 22%) (p < 0.05). Gram-negative bacilli were infrequent colonizers and neither did the incidence of infection with these organisms increase nor did resistance develop in any group. The infection rates were not different among the treatment groups. Thus, a narrow-spectrum antistaphylococcal penicillin may offer an advantage in terms of both prophylaxis for cardiac operations and hospital costs.