Trimethoprim-sulfamethoxazole.
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Biomedical subjects
Publications and source records attributed to M N Swartz.
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Ninety-nine patients treated with penicillin G potassium, cephalothin sodium, or vancomycin hydrochloride were studied to evaluate single-drug therapy for nonenterococcal streptococcal endocarditis. Eighty-six patients survived; of these, 66 received penicillin alone. The maximum serum bactericidal titer obtained at the expected nadir of serum antibiotic concentration was 1:8 or greater in 70 (95%) of the 74 patients studied. No relapse occurred among the 66 patients treated wih penicillin. Only one patient experienced a relapse that occurred following therapy with suboptimal doses of vancomycin. Distinct second episodes of endocarditis occurred in five patients. While 13 patients died, none died of intractable infection. The treatment of endocarditis due to penicillin-susceptible streptococci with high-dose parenteral penicillin or a bactericidal penicillin substitute for four weeks or longer results in bacteriologic cure rates comparable with those achieved with combined penicillin-streptomycin regimens.
Since the initial description of Legionnaires' disease 2 years ago, a clearer picture of its clinical manifestations has emerged as a result of investigations of further epidemics and studies of laboratory-confirmed sporadic cases. Although individual clinical features are not sufficiently distinctive to distinguish Legionnaires' disease from other types of acute pneumonia, a composite can provide a sufficiently characteristic clinical profile to indicate the likelihood of this diagnosis. Such a profile includes high fever (above 39.4 degrees C); recurrent chills; relative bradycardia; early gastrointestinal symptoms (particularly diarrhea); prominent myalgias; microscopic hematuria; liver function abnormalities; toxic encephalopathy; nonproductive cough; absence of bacterial pathogens on Gram stain and culture of transtracheal aspirate; progression from patchy bronchopneumonia to lobar and multilobar consolidation; and frequently prompt and sometimes dramatic response to treatment with erythromycin.
Mating experiments have shown that high-level resistance (minimal inhibitory concentration greater than 2,000 microgram/ml) to streptomycin and kanamycin, and resistance to penicillin-streptomycin and penicillin-kanamycin synergism are transferable by conjugation from resistant clinical isolates of enterococci to a sensitive recipient strain. Cesium chloride-ethidium bromide ultracentrifugation revealed a satellite (plasmid) band in resistant clinical isolates and the transconjugant strains but not in the sensitive recipient. Examination of these satellite bands by agarose gel electrophoresis and electron microscopy demonstrated a common plasmid with a weight of 45 megadaltons. Novobiocin treatment of a resistant clinical isolate produced simultaneous loss of high-level resistance to streptomycin and kanamycin, and of resistance to penicillin-aminoglycoside synergism. These results suggest that (a) high-level resistance to streptomycin and kanamycin among some clinical isolates of enterococci is associated with a 45 megadalton plasmid, and (b) the same plasmid is also responsible for the resistance to penicillin-aminoglycoside synergism observed in these strains.
Clinical isolates of enterococci (Streptococcus faecalis) with high-level resistance to both streptomycin and kanamycin (minimal inhibitory concentration >2,000 mug/ml), and resistant to synergism with penicillin and streptomycin or kanamycin were examined for aminoglycoside-inactivating enzymes. All of the 10 strains studied had streptomycin adenylyltransferase and neomycin phosphotransferase activities; the latter enzyme phosphorylated amikacin as well as its normal substrates, such as kanamycin. Substrate profiles of the neomycin phosphotransferase activity suggested that phosphorylation occurred at the 3'-hydroxyl position, i.e., aminoglycoside 3'-phosphotransferase. A transconjugant strain, which acquired high-level aminoglycoside resistance and resistance to antibiotic synergism after mating with a resistant clinical isolate, also acquired both enzyme activities. Quantitative phosphorylation of amikacin in vitro by a sonicate of the transconjugant strain inactivated the antibiotic, as measured by bioassay, and the phosphorylated drug failed to produce synergism when combined with penicillin against a strain sensitive to penicillin-amikacin synergism.No differences were found in the sensitivity of ribosomes from a sensitive and resistant strain when examined in vitro using polyuridylic acid directed [(14)C]-phenylalanine incorporation in the presence of streptomycin, kanamycin, or amikacin. Therefore, we conclude that aminoglycoside-inactivating enzymes are responsible for the aminoglycoside resistance, and resistance to antibiotic synergism observed in these strains.
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Certain plasmids can be eliminated by exposure to growth-inhibiting concentrations of novobiocin. Novobiocin cured 8 of 14 plasmids (13 R-plasmids and an F' lac) among one or another of four different bacterial hosts.
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Thirty-nine patients with spinal epidural abscess were evaluated at the Massachusetts General Hospital between 1947 and 1974. Twenty had acute symptoms, and purulent epidural collections were present; 19 had prolonged courses, and epidural granulation tissue was observed at operation. Staphylococcus aureus was the most common etiologic agent (57 per cent), followed by streptococci (18 per cent) and gram-negative bacilli (13 per cent). The source of infection was osteomyelitis in 38 per cent of cases and bacteremia in 26 per cent. In 16 per cent epidural abscess was due to postoperative infection. The progression from spinal ache to root pain to weakness followed by paralysis continues to be characteristic of spinal epidural abscess. Although the disease is uncommon, the complications are so serious that prompt diagnosis and treatment are of paramount importance. The combination of back pain with fewer and local tenderness is an indication for cerebrospinal-fluid examination and, depending on the results, immediate performance of myelography.
A strain of Salmonella typhimurium appeared sequentially in three patients in a burn unit, and epidemiological study suggested the occurrence of person-to-person spread. This organism was responsible for both colonisation and invasive infection in these patients whose burn surfaces were receiving topical treatment with 0.5% silver nitrate (AgNO3) solution. The antibiotic and metal ionsusceptibility pattern of this strain of S. typhimurium was unique and disturbing: resistant to silver nitrate, mercuric chloride, ampicillin, chloramphenicol, tetracycline, streptomycin, and sulphonamides. This pattern of multiple resistances could be transferred by invitro mating experiments to sensitive recipient strains of Escherichia coli and S. typhimurium. Further transfer of these resistances could be consumated between different strains of E. coli. A survey of other salmonella strains isolated from patients in this hospital without thermal burns did not reveal this pattern of resistance. Also, strains of S. typhimurium, isolated elsewhere and showing simultaneous resistance to both ampicillin and chloramphenicol, were not resistant to AgNO3 in vitro. The very real danger of this strain of S. typhimurium in burn units stems from its resistance to the two most effective antibiotics (ampicillin and chloramphenicol) available for systemic therapy; and this threat may be compounded through the selection effected by the widespread topical use of AgNO3 solutions and sulphonamide preparations on burned surfaces.
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