Search PubMed⌕ Search

Biomedical subjects

M N Swartz

Publications and source records attributed to M N Swartz.

At least 19 recordsLinked to original sources
PubMed1996

Paracoccidioidomycosis of bones and joints. A clinical, radiologic, and pathologic study of 9 cases.

Paracoccidioidomycosis is a systemic fungal infection endemic to Central and South America. It is associated with a broad spectrum of clinical manifestations and has been classified into acute and chronic forms. The latter is the most common type and usually affects male agricultural workers in rural communities. The disease typically begins in the lungs producing varying degrees of parenchymal damage, and in a significant number of cases the organism spreads through bronchogenic, lymphatic, or hematogenous routes to involve 1 or more organs. Bone and joint infection is relatively uncommon and has not been well described in the English literature. Much of the information on this form of the disease has been derived from radiographic and autopsy studies on patients with severe or fatal infections in whom skeletal involvement was a minor or incidental finding. We describe our experience with 9 cases in which osteoarticular manifestations were the sole or 1 of the few major complications of the disease. All 9 patients were male, from 9 to 49 years of age (mean, 36.6 yr). Six were farmers. Evidence of visceral infection was present in 6 patients, in all of whom the lungs were considered the primary site of disease. The osteoarticular lesions were symptomatic in all cases, with the duration of symptoms ranging from 1 week to 2 years. The lesions were centered in bone in 2 cases: they manifested radiographically as circumscribed areas of lysis with or without a rim of sclerosis. The disease was centered in joints in 7 cases; the associated radiographic changes included evidence of joint effusion, periarticular bony erosions, and narrowing of the joint space. Biopsy of the involved skeletal site revealed compact or loose granulomas containing variable numbers of fungi. Although follow-up information was not available for all patients, those treated with TMP-SMX (and 1 patient who also received amphotericin B) and who were followed had prompt resolution of their signs and symptoms. Our findings substantiate some of what is known about the epidemiology of bone and joint involvement in chronic paracoccidioidomycosis. Our patients exhibited features of skeletal infection that have not been emphasized previously, however, including 1) frequent involvement of large joints or long bones of the extremities, 2) presentation with relatively rapidly developing musculoskeletal symptoms, and 3) manifestation as a solitary joint or bone lesion with or without concurrent clinically detectable pulmonary disease. Bone and joint paracoccidioidomycosis should be considered in the differential diagnosis in patients who have skeletal lesions with or without pulmonary involvement and have either lived in or traveled through endemic areas. Early diagnosis and treatment with antifungal medications can achieve an excellent outcome with limited local sequelae.

Adult↗
PubMed1994

Hospital-acquired infections: diseases with increasingly limited therapies.

About 5% of patients admitted to acute-care hospitals acquire nosocomial infections. A variety of factors contribute: increasing age of patients; availability, for treatment of formerly untreatable diseases, of extensive surgical and intensive medical therapies; and frequent use of antimicrobial drugs capable of selecting a resistant microbial flora. Nosocomial infections due to resistant organisms have been a problem ever since infections due to penicillinase-producing Staphylococcus aureus were noted within a few years of the introduction of penicillin. By the 1960s aerobic Gram-negative bacilli had assumed increasing importance as nosocomial pathogens, and many strains were resistant to available antimicrobials. During the 1980s the principal organisms causing nosocomial bloodstream infections were coagulase-negative staphylococci, aerobic Gram-negative bacilli, S. aureus, Candida spp., and Enterococcus spp. Coagulase-negative staphylococci and S. aureus are often methicillin-resistant, requiring parenteral use of vancomycin. Prevalence of vancomycin resistance among enterococcal isolates from patients in intensive care units has increased, likely due to increased use of this drug. Plasmid-mediated gentamicin resistance in up to 50% of enterococcal isolates, along with enhanced penicillin resistance in some strains, leaves few therapeutic options. The emergence of Enterobacteriaceae with chromosomal or plasmid-encoded extended spectrum beta-lactamases presents a world-wide problem of resistance to third generation cephalosporins. Control of these infections rests on (i) monitoring infections with such resistant organisms in an ongoing fashion, (ii) prompt institution of barrier precautions when infected or colonized patients are identified, and (iii) appropriate use of antimicrobials through implementation of antibiotic control programs.

Candidiasis↗
PubMed1993

Acute bacterial meningitis in adults. A review of 493 episodes.

BACKGROUND AND METHODS: To characterize acute bacterial meningitis in adults, we reviewed the charts of all persons 16 years of age or older in whom acute bacterial meningitis was diagnosed at Massachusetts General Hospital from 1962 through 1988. We included patients who were admitted after initial treatment at other hospitals. RESULTS: During the 27-year period, 445 adults were treated for 493 episodes of acute bacterial meningitis, of which 197 (40 percent) were nosocomial. Gram-negative bacilli (other than Haemophilus influenzae) caused 33 percent of the nosocomial episodes but only 3 percent of the community-acquired episodes. In the 296 episodes of community-acquired meningitis, the most common pathogens were Streptococcus pneumoniae (37 percent), Neisseria meningitidis (13 percent), and Listeria monocytogenes (10 percent); these organisms accounted for only 8 percent of the nosocomial episodes. Only 19 of the 493 episodes of meningitis (4 percent) were due to H. influenzae. Nine percent of all patients had recurrent meningitis; many had a cerebrospinal fluid leak. Seizures occurred in 23 percent of patients with community-acquired meningitis, and 28 percent had focal central nervous system findings. Risk factors for death among those with single episodes of community-acquired meningitis included older age (> or = 60 years), obtunded mental state on admission, and seizures within the first 24 hours. Among those with single episodes, the in-hospital mortality rate was 25 percent for community-acquired and 35 percent for nosocomial meningitis. The overall case fatality rate was 25 percent and did not vary significantly over the 27 years. CONCLUSIONS: In our large urban hospital, a major proportion of cases of acute bacterial meningitis in adults were nosocomial. Recurrent episodes of meningitis were frequent. The overall mortality rate remained high.

Acute Disease↗
PubMed1990

Mutants of Escherichia coli K-12 exhibiting reduced killing by both quinolone and beta-lactam antimicrobial agents.

Norfloxacin, ofloxacin, and other new quinolones, which are antagonists of the enzyme DNA gyrase, rapidly kill bacteria by largely unknown mechanisms. Earlier, we isolated, after mutagenesis, Escherichia coli DS1, which exhibited reduced killing by quinolones. We evaluated the killing of DS1 and several other strains by quinolones and beta-lactams. In time-killing studies with norfloxacin, DS1 was killed 1 to 2 log10 units compared to 4 to 5 log10 units for the wild-type parent strain KL16, thus revealing that DS1 is a high-persistence (hip) mutant. DS1 exhibited a similar high-persistence pattern for the beta-lactam ampicillin and reduced killing by drugs that differed in their affinities for penicillin-binding proteins, including cefoxitin, cefsulodin, imipenem, mecillinam, and piperacillin. Conjugation and P1 transduction studies identified a novel mutant locus (termed hipQ) in the 2-min region of the DS1 chromosome necessary for reduced killing by norfloxacin and ampicillin. E. coli KL500, which was isolated for reduced killing by norfloxacin without mutagenesis, exhibited reduced killing by ampicillin. E. coli HM23, a hipA (34 min) mutant that was isolated earlier for reduced killing by ampicillin, also exhibited high persistence to norfloxacin. DS1 differed from HM23, however, in the map location of its hip mutation, lack of cold sensitivity, and reduced killing by coumermycin. Results of these studies with strains DS1, KL500, and HM23 demonstrate overlap in the pathways of killing of E. coli by quinolones and beta-lactams and identify hipQ, a new mutant locus that is involved in a high-persistence pattern of reduced killing by norfloxacin and ampicillin.

Anti-Bacterial Agents↗
PubMed1989

Mechanisms of quinolone resistance in Escherichia coli: characterization of nfxB and cfxB, two mutant resistance loci decreasing norfloxacin accumulation.

Two genetic loci selected for norfloxacin (nfxB) and ciprofloxacin (cfxB) resistance were characterized. Both mutations have previously been shown to confer pleiotropic resistance to quinolones, chloramphenicol, and tetracycline and to decrease expression of porin outer-membrane protein OmpF. nfxB was shown to map at about 19 min and thus to be genetically distinct from ompF (21 min), and cfxB was shown to be very closely linked to marA (34 min). cfxB was dominant over cfxB+ in merodiploids, in contrast to other quinolone resistance mutations. The two loci appear to interact functionally, because nfxB was not expressed in the presence of marA::Tn5. Both nfxB and cfxB decreased the expression of ompF up to 50-fold at the posttranscriptional level as determined in strains containing ompF-lacZ operon and protein fusions. Both mutations also decreased norfloxacin accumulation in intact cells. This decrease in accumulation was abolished by energy inhibitors and by removal of the outer membrane. These findings, in conjunction with those of Cohen et al. (S. P. Cohen, D. C. Hooper, J. S. Wolfson, K. S. Souza, L. M. McMurry, and S. B. Levy, Antimicrob. Agents Chemother. 32:1187-1191, 1988), suggest a model for quinolone resistance by decreased permeation in which decreased diffusion through porin channels in the outer membrane interacts with a saturable drug efflux system at the inner membrane.

Anti-Infective Agents↗
PubMed1989

Isolation and characterization of an Escherichia coli strain exhibiting partial tolerance to quinolones.

Quinolone antimicrobial agents rapidly kill bacteria by largely unknown mechanisms. To study this phenomenon, a strain of Escherichia coli inhibited but inefficiently killed by (i.e., partially tolerant to) norfloxacin was isolated and characterized. E. coli KL16 (norfloxacin MIC, 0.10 microgram/ml; MBC, 0.20 microgram/ml) was mutagenized with nitrosoguanidine and cyclically exposed to 3 micrograms of norfloxacin per ml. After five cycles, a bacterial strain (DS1) which was killed 1,000-fold less than KL16 during 3 h of drug exposure was isolated. The MIC and MBC of norfloxacin for DS1 were 0.20 and 1.5 micrograms/ml, respectively. Over a range of norfloxacin concentrations, DS1 was killed 2 to 4 orders of magnitude less than KL16. DS1 grew more slowly than KL16 but after normalization for growth rate was killed four times less rapidly than KL16 at drug concentrations 10-fold higher than respective MICs. DS1 and KL16 cells filamented similarly upon exposure to norfloxacin. DS1 exhibited tolerance to other DNA gyrase A subunit antagonists (ofloxacin and ciprofloxacin) and DNA gyrase B subunit antagonists (novobiocin and coumermycin) but not to the aminoglycoside gentamicin, suggesting involvement of DNA gyrase. DS1 also appeared to be minimally tolerant to the beta-lactam cefoxitin. DS1 exhibited increased susceptibility to the mutagen methyl methanesulfonate, implying a defect in DNA repair. This report describes the first use of quinolone enrichment for isolation of a bacterial strain partially tolerant to quinolones. The study of defects in such tolerant strains offers an approach to an increased understanding of the mechanisms of bacterial killing by quinolones.

Anti-Infective Agents↗
PubMed1989

Effects of inhibition of the B subunit of DNA gyrase on conjugation in Escherichia coli.

Antagonism of the DNA gyrase B subunit in the donor bacterium by coumermycin or thermal inactivation inhibited transfer of plasmid R64drd-11. Coumermycin also inhibited Hfr transfer, with kinetics after drug removal suggesting that transfer resumed from the point of inhibition, in contrast to inhibition with nalidixic acid, after which transfer reinitiated from the origin of transfer.

Aminocoumarins↗
PubMed1987

Mechanisms of action of and resistance to ciprofloxacin.

Ciprofloxacin and other newer quinolone antimicrobial agents exhibit increased potency and decreased frequency of spontaneous bacterial resistance in comparison with older analogues such as nalidixic acid. New and published observations on the mechanisms of action of and resistance to ciprofloxacin in Escherichia coli are presented and discussed. Genetic and biochemical studies have identified the A subunit of the essential bacterial enzyme DNA gyrase as a target of ciprofloxacin and other quinolones. For a series of quinolones, inhibition of purified DNA gyrase correlated with antibacterial activity. The bactericidal activity of ciprofloxacin and ofloxacin is, in contrast to that of certain other quinolones, somewhat less affected by rifampin and cell starvation, suggesting the existence of a site of drug action in addition to DNA gyrase. The frequency of selection of spontaneous single-step resistance mutants of E. coli was more than 100-fold lower with ciprofloxacin than with nalidixic acid. Strains highly resistant to ciprofloxacin could, nevertheless, be selected by serial passage on drug-containing agar. Two mutations contributing to this high level of resistance were analyzed. One, designated cfxA, conferred a 16-fold increase in drug resistance and mapped in a location consistent with a gyrA mutation; similar increases in resistance to ciprofloxacin were seen with gyrA mutations selected for resistance to other quinolones. The other mutation, cfxB, conferred pleiotropic resistance to ciprofloxacin, tetracycline, and chloramphenicol and appeared to be an allele of the multiple antibiotic resistance gene marA. The mutation cfxB was associated with a decreased amount of porin outer membrane protein OmpF, suggesting that drug permeation may occur in part through this channel. In summary, the A subunit of DNA gyrase is a target of ciprofloxacin and other quinolones. Ciprofloxacin resistance appears to occur both by mutation in this target and by alteration of drug permeation through the outer membrane of the cell.

Anti-Bacterial Agents↗