Computed tomography of the head before a lumbar puncture in suspected meningitis -- is it helpful?
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Brain↗
Biomedical subjects
N H Steigbigel
Publications and source records attributed to N H Steigbigel.
Acute (ascending) cholangitis.
Cholangitis is an infection of an obstructed biliary system, most commonly due to common bile duct stones. Bacteria reach the biliary system either by ascent from the intestine or by the portal venous system. Once the biliary system is colonized, biliary stasis allows bacterial multiplication, and increased biliary pressures enable the bacteria to penetrate cellular barriers and enter the bloodstream. Patients with cholangitis are febrile, often have abdominal pain, and are jaundiced. A minority of patients present in shock with hypotension and altered mentation. There is usually a leukocytosis, and the alkaline phosphatase and bilirubin levels are generally elevated. Noninvasive diagnostic techniques include sonography, which is the recommended initial imaging modality. Standard CT, helical CT cholangiography, and magnetic resonance cholangiography often add important information regarding the type and level of obstruction. Endoscopic sonography is a more invasive means of obtaining high-quality imaging, and endoscopic or percutaneous cholangiography offers the opportunity to perform a therapeutic procedure at the time of diagnostic imaging. Endoscopic modalities currently are favored over percutaneous procedures because of a lower risk of complication. Treatment includes fluid resuscitation and antimicrobial agents that cover enteric flora. Biliary decompression is required when patients do not rapidly respond to conservative therapy. Definitive therapy can be performed by a surgical, percutaneous, or endoscopic route; the last is favored because it is the least invasive and has the lowest complication rate. Overall prognosis depends on the severity of the illness at the time of presentation and the cause of the biliary obstruction.
Acute Disease↗
Fellowship training in infectious diseases: a report from the regional and national meetings of infectious diseases division chiefs and program directors.
During the 2-year period April 1995 to April 1997, six regional meetings and one national meeting of division chiefs and program directors of adult infectious diseases programs in the United States were held to review fellowship training. Herein, we report data on job availability and job selection for recently graduated fellows. We summarize discussions on decreasing the number of fellows in training, and we outline suggested components of a core clinical curriculum and of three training tracks--clinician track, clinical investigator track, and basic investigator track.
Adult↗
Cholangitis: pathogenesis, diagnosis, and treatment.
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Acquired Immunodeficiency Syndrome↗
Low occupational risk of human immunodeficiency virus infection among dental professionals.
We studied 1309 dental professionals (1132 dentists, 131 hygienists, and 46 assistants) without behavioral risk factors for the acquired immunodeficiency syndrome (AIDS) to determine their occupational risk for infection with human immunodeficiency virus (HIV). Subjects completed questionnaires on behavior; type, duration, and location of their dental practice; infection-control practices; and estimated numbers of potential occupational exposures to HIV. Serum samples were tested for antibodies to HIV and to hepatitis B surface antigen (unvaccinated subjects). Fifty-one percent of the subjects practiced in locations where many cases of AIDS have been reported. Seventy-two percent treated patients who had AIDS or were at increased risk for it. Ninety-four percent reported accidental puncturing of the skin with instruments used in treating patients. Adherence to recommended infection-control practices was infrequent. Twenty-one percent of unvaccinated subjects had antibodies to hepatitis B surface antigen. Only one dentist without a history of behavioral risk factors for AIDS had serum antibodies to HIV. We conclude that despite infrequent compliance with recommended infection-control precautions, frequent occupational exposure to persons at increased risk for HIV infection, and frequent accidental puncturing of the skin with sharp instruments, dental professionals are at low occupational risk for HIV infection.
Accidents, Occupational↗
Lack of association of Streptococcus bovis with noncolonic gastrointestinal carcinoma.
Since previous studies have shown an increased fecal carriage rate of Streptococcus bovis in patients with carcinoma of the colon, a study was undertaken to determine the fecal carriage rate of this organism in patients with gastrointestinal carcinoma of noncolonic origin. Organisms identified as S. bovis were isolated on fecal culture from 10 of 82 (12%) controls, 19 of 94 (20%) individuals with noncolonic gastrointestinal carcinoma, and 12 of 80 (15%) patients with other gastrointestinal disorders. Subjects with noncolonic gastrointestinal carcinoma did not have a fecal carriage rate of S. bovis significantly different from that in controls. A literature review of 251 patients with S. bovis septicemia identified at least 89 (35%) with neoplasms of the colon. Only nine patients (4%) with gastrointestinal neoplasms of other than colonic origin were noted. At present, the indication for an intensive evaluation of the upper gastrointestinal tract in individuals with S. bovis bacteremia is substantially less than that for the colon.
Adult↗
HTLV-I-specific antibody in AIDS patients and others at risk.
Serum samples from 440 acquired immunodeficiency syndrome (AIDS) patients or individuals at risk for AIDS were examined by the enzyme-linked immunosorbent assay technique for antibodies to HTLV-I core proteins. Specific antibodies were detected in 7% of AIDS patients, 7% of patients with lymphadenopathy, 0% of healthy homosexual men, and 12% of healthy Haitians. When findings in homosexual men were analysed separately, the prevalence for homosexual men with lymphadenopathy was 7% and for homosexuals with AIDS, 6%. Antibody titres ranged from 77 to 74 000. The antibody-positive cases included intravenous drug users, a Haitian AIDS patient, a recipient of multiple blood transfusions, and homosexual men. Haemophiliacs were not examined. Although HTLV-I-specific antibodies are more prevalent in AIDS patients than in healthy US donors, the difference is not sufficient to suggest an association of HTLV-I with the disease. The low rate may indicate an opportunisitic infection of AIDS patients by HTLV-I, or a crossreaction with the recently described HTLV variant, HTLV-III, believed to be the aetiological agent of AIDS. Whether HTLV-I normally exerts immune suppressive effects in vivo with biological consequences remains to be determined.
Acquired Immunodeficiency Syndrome↗
Susceptibilities of bacterial and fungal urinary tract isolates to desferrioxamine.
Desferrioxamine, a safe and effective iron chelator, was evaluated for its antibacterial and antifungal activity. The susceptibilities of 124 urinary tract isolates and 28 clinical isolates of Neisseria gonorrhoeae to desferrioxamine concentrations that are readily achievable in urine were determined. Of all isolates, 27% were inhibited by a concentration of less than or equal to 12.5 mM. Proteus mirabilis and N. gonorrhoeae isolates were particularly susceptible to the chelator. Desferrioxamine appears to have limited potential as an antibacterial agent.
Anti-Bacterial Agents↗
Gentamicin uptake in Staphylococcus aureus possessing plasmid-encoded, aminoglycoside-modifying enzymes.
[3H]gentamicin uptake and killing were studied in three strains of gentamicin-resistant Staphylococcus aureus possessing plasmid-encoded, gentamicin-modifying enzymes and in three isogenic, enzyme-free, gentamicin-susceptible derivatives. At low (less than or equal to 2.0 micrograms/ml) concentrations of gentamicin, uptake by resistant organisms was impaired compared with that of susceptible strains, and no killing was noted. In contrast, at higher (2.5 to 10.0 micrograms/ml) concentrations (which were below the MIC for the resistant strains), rapid gentamicin uptake similar to that seen in susceptible isolates was observed. Although growth inhibition at these concentrations was apparent, there was no loss of viability in resistant strains. Consistently, the membrane H+-ATPase inhibitor N,N'-dicyclohexyl carbodiimide caused resistant strains to take up low concentrations (1.0 microgram/ml) of gentamicin at rates comparable to those seen in susceptible organisms without causing an associated loss of viability. These studies show differences between gentamicin uptake in S. aureus and streptomycin uptake in Escherichia coli (Dickie et al., Antimicrob. Agents Chemother. 14:569-580, 1978) regarding the kinetics of uptake in resistant strains with plasmid-encoded aminoglycoside-modifying enzymes. Specifically, they suggest that for 2-deoxystreptamine compounds such as gentamicin, ribosomal binding followed by accelerated uptake and subsequent interference with cell growth may occur without invariably being associated with lethal effect.
Dicyclohexylcarbodiimide↗
Immunodeficiency in female sexual partners of men with the acquired immunodeficiency syndrome.
Because the current outbreak of acquired immunodeficiency syndrome (AIDS) among previously healthy adults may be caused by a transmissible biologic agent, and because it may be preceded by immunologic abnormalities with or without a prodromal illness, we studied seven female sexual partners of male patients with the syndrome. The male patients were all drug abusers. One of the seven women was found to have the full-blown syndrome, a second had an illness consistent with the prodrome of AIDS (generalized lymphadenopathy, lymphopenia, and a decreased ratio of helper to suppressor T cells), and four others had generalized lymphadenopathy or lymphopenia, with or without a decreased ratio of helper to suppressor T cells. Only one woman had no abnormalities. These findings suggest that AIDS may be transmitted between heterosexual men and women.
Acquired Immunodeficiency Syndrome↗
Penicillin therapy of experimental endocarditis induced by tolerant Streptococcus sanguis and nontolerant Streptococcus mitis.
The response of tolerant Streptococcus sanguis and nontolerant Streptococcus mitis infections to penicillin therapy was compared in the rabbit model of endocarditis. The minimal inhibitory and bactericidal concentrations of penicillin were 0.1 and 0.1 mug/ml, respectively, for S. mitis and 0.05 and 6.2 mug/ml, respectively, for S. sanguis. Time-kill studies done in vitro with penicillin concentrations of 2 and 20 mug/ml demonstrated minimal killing of the tolerant strain, with a 3 log difference in survival between the two strains after 24 and 48 h. Both strains produced endocarditis with comparable bacterial densities on the valvular vegetations. Rabbits were treated with procaine penicillin G in two dosage regimens, 80,000 or 5,000 U/kg given every 8 h. There was no difference between bacterial densities in valvular vegetations removed from rabbits infected with either strain after 2, 4, or 6 days of treatment with the high-dose regimen (serum penicillin concentration at 0.5 h, 9.4 mug/ml), despite the fact that serum bactericidal activity against the tolerant strain at 0.5 h was minimal. With the low-dose penicillin regimen (serum concentration at 0.5 h, 2.5 mug/ml), therapy was significantly less effective in the tolerant group only after 6 days of treatment. Similar results were obtained when penicillin was administered in low and high doses to prevent infection. In this animal model of infection, penicillin tolerance was associated with a diminished response to penicillin therapy only when the dose was severely restricted. In the high-dose regimen, there was no difference in the response to penicillin therapy between animals infected with either strain, despite the presence of only minimal serum bactericidal activity in the rabbits infected with the tolerant strain.
Animals↗
Effect of penicillin on the adherence of Streptococcus sanguis in vitro and in the rabbit model of endocarditis.
The effect of penicillin treatment of Streptococcus sanguis in vitro, on subsequent bacterial density in the bloodstream and on cardiac valves in the rabbit model of endocarditis was studied. As experimental tools for this study, isogenic pairs of S. sanguis differing in resistance to streptomycin or rifampin were prepared by genetic transformation. Rabbits with traumatized heart valves received an intravenous inoculation of penicillin treated (1 mug/ml) and untreated S. sanguis, each marked by resistance to either streptomycin or rifampin. The number of penicillin-treated and untreated bacteria attached to the valvular surfaces was determined by differential counting on streptomycin or rifampin containing media. Penicillin pretreatment reduced cardiac valve colonization 5 min after inoculation ("adherence ratio" x 10(8) was 4.11 for the control and 3.66 for the penicillin-treated bacteria, P < 0.001). The results were not due to differences in serum killing or bacterial densities in the bloodstream. There was no difference in valvular bacterial densities 24 h after bacterial inoculation (adherence ratio x 10(8), 7.26 untreated vs. 6.34 penicillin-pretreated, P > 0.10). In vitro experiments were performed using platelet-fibrin surfaces to test the possibility that penicillin-induced loss of lipoteichoic acid was responsible for decreased streptococcal adherence. Pretreatment of S. sanguis cultures with inhibitory concentrations of penicillin or with antiserum against lipoteichoic acid and precoating of the platelet-fibrin surfaces with lipoteichoic acid, all caused reduction in bacterial adherence. The findings are interpreted as support for the role of lipoteichoic acid as an adhesin in S. sanguis interactions with particular host tissue surfaces.
Adhesiveness↗
Therapy of methicillin-resistant Staphylococcus epidermidis experimental endocarditis.
Antibiotic therapy of methicillin-resistant Staphylococcus epidermidis endocarditis was investigated with the rabbit endocarditis model. Time-kill studies in vitro demonstrated that gentamicin and rifampin had the most rapid early bactericidal rates. With rifampin alone, rifampin-resistant subpopulations emerged. Combinations of antibiotics with gentamicin or rifampin in vitro did not significantly alter the killing rate but prevented emergence of subpopulations resistant to the latter. In the rabbit endocarditis model, gentamicin and vancomycin were the most effective single antibiotic regimens in terms of ability to reduce the bacterial densities on cardiac valve vegetations. Five treatment regimens were equally effective, including vancomycin, gentamicin, vancomycin plus rifampin or gentamicin, and rifampin plus gentamicin. The three-drug combination of vancomycin, rifampin, and gentamicin did not significantly improve the results. Cephalothin therapy was significantly less effective than any of the regimens noted above. It was no more effective than no treatment at 2 days and was only slightly more effective at 4 days. This result with cephalothin treatment was not predicted by routine types of in vitro antibiotic susceptibility testing. Treatment of rabbits with methicillin or cephalothin was associated with an increase in the subpopulation of bacteria resistant to the respective drugs. A number of regimens show potential for therapy of these infections, including vancomycin plus rifampin or gentamicin, rifampin plus gentamicin, and vancomycin alone.
Animals↗
Gentamicin uptake in wild-type and aminoglycoside-resistant small-colony mutants of Staphylococcus aureus.
Gentamicin uptake and killing were studied in aminoglycoside-susceptible wild-type Staphylococcus aureus strains and aminoglycoside-resistant small-colony mutants selected by gentamicin from these strains. In wild-type S. aureus three phases of gentamicin accumulation were noted, and killing occurred during the last and most rapid phase of uptake. Uptake and killing were abolished by anaerobic growth and sodium azide, suggesting that energy-dependent active drug transport required respiration. Treatment of wild-type strains with the uncouplers N,N'-dicyclohexyl carbodiimide (DCCD) and carbonyl cyanide-m-chlorophenyl hydrazone showed disparate effects on gentamicin uptake, producing enhanced and diminished accumulations, respectively. Small-colony mutants demonstrated markedly deficient uptake compared with the wild-type strains and were not killed by gentamicin in concentrations up to 10 mug/ml. Several classes of aminoglycoside-resistant mutant strains are described. One mutant strain was a menadione auxotroph which, when grown in the presence of menadione, exhibited normal gentamicin uptake and killing. Gentamicin uptake and killing in this strain were abolished by KCN when the strain was grown in a medium supplemented with menadione. The membrane adenosine triphosphatase inhibitor DCCD was lethal for this mutant but not for other mutants or wild-type strains. Preincubation with menadione prevented the lethal effect of DCCD, and this strain demonstrated normal gentamicin accumulation when exposed to both DCCD and menadione. A second mutant strain demonstrated both gentamicin uptake and killing in the presence but not the absence of DCCD. Studies with small-colony mutants of S. aureus indicated that the defect in aminoglycoside uptake is very likely related to an inability to generate or maintain energized membranes from respiration. These studies suggest that the membrane energization associated with active aminoglycoside accumulation requires electron transport for the generation of a protonmotive force.
Aminoglycosides↗
Antibiotic activity in vitro against methicillin-resistant Staphylococcus epidermidis and therapy of an experimental infection.
Staphylococcus epidermidis is a major pathogen in early prosthetic valve endocarditis and cerebrospinal fluid shunt infections. Approximately 10 to 15% of hospital isolates are methicillin resistant. Ten clinically significant isolates of the latter were collected for antibiotic studies in vitro and in an experimental infection in animals. Time-kill studies of five strains showed gentamicin to be the single most effective antibiotic; however, dwarf colony variants emerged as survivors with two of these strains when challenged with gentamicin alone. The addition of a second antibiotic to gentamicin did not significantly improve the bactericidal rate but prevented the emergence of variant strains. A blood culture isolate of methicillin-resistant S. epidermidis combined with 5% hog gastric mucin was used to establish an experimental intraperitoneal infection in mice. Neither methicillin nor nafcillin treatment reduced mortality below that of untreated animals. Cephalothin treatment delayed early mortality but did not diminish overall mortality. Gentamicin was the most effective single antibiotic, and gentamicin in combination with vancomycin was the most effective regimen overall. The combination of rifampin plus vancomycin was as effective as gentamicin alone. The combinations of cephalothin or nafcillin with gentamicin and cephalothin with vancomycin demonstrated antagonism. The antagonism was not due to multiple injections or drug-drug inactivation.
Animals↗
Streptococcus bovis septicemia and carcinoma of the colon.
We prospectively studied patients with Streptococcus bovis septicemia for the presence of gastrointestinal lesions. This study was prompted by our reported findings of the association of fecal carriage of S. bovis with carcinoma of the colon. We studied 29 patients with 30 episodes of S. bovis septicemia. Fifteen completed gastrointestinal evaluations that included colonscopy, surgery, or autopsy. Eight of these had carcinoma of the colon, three had adenomatous polyps of the colon without carcinoma, and two had carcinoma of the esophagus. The 14 patients who did not have complete evaluations included one each with carcinoma of the stomach, gastric lymphoma, and adenomatous polyp of the colon and three with colonic masses not further delineated. Nineteen patients had no gastrointestinal signs or symptoms or stools positive for occult blood at admission. The results of our study suggest that all patients with S. bovis septicemia need aggressive evaluation of the gastrointestinal tract, especially the colon.
Adenocarcinoma↗
Infective endocarditis. Part III. Prevention of bacterial endocarditis.
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Animals↗
Single and combination antibiotic therapy of Staphylococcus aureus experimental endocarditis: emergence of gentamicin-resistant mutants.
The efficacy of nafcillin and gentamicin used alone and in combination at doses giving serum concentrations comparable to those achieved in patients was studied in rabbits with experimental Staphylococcus aureus endocarditis. The organism used was a penicillinase-producing, methicillin-susceptible, clinical isolate. The addition of gentamicin to nafcillin significantly increased the rate of killing of organisms in valvular vegetations, compared to the effect of nafcillin alone. Gentamicin alone delayed mortality but was not effective in reducing the bacterial populations of the vegetations. Bacteremia persisted in the animals treated with gentamicin alone, in contrast to the groups treated with nafcillin or the combination. Selection of a subpopulation of aminoglycoside-resistant small-colony variants occurred in animals treated with gentamicin alone. This variant was subsequently employed in the rabbit model and produced endocarditis, metastatic infection, and bacteremia comparable to those caused by the parent strain. Animals with infection produced by the variant died later than animals infected by the parent strain. Nafcillin was equally effective in reducing the population of both parent and variant strains in vitro and in therapy of the infected animals. Population studies showed the variant to be a mutant emerging at a rate of 1.9 x 10(-7). It was shown to differ from the parent strain in coagulase and hemolysin production, colonial morphology, and aminoglycoside susceptibility, but was similar by light and electron microscopy and in phage type, pigmentation of colonies, deoxyribonuclease production, mannitol fermentation, and growth rate.
Animals↗