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D M Shlaes

Publications and source records attributed to D M Shlaes.

At least 73 records · Page 4Linked to original sources
PubMed1989

Escherichia coli susceptible to glycopeptide antibiotics.

Mutants of Escherichia coli susceptible to vancomycin were isolated after mutagenesis with nitrosoguanidine. One such mutant was studied extensively. Multiple regression analysis of the relationship between physical properties of 20 glycopeptides and their in vitro activities against the vancomycin-susceptible mutant revealed a significant correlation with molecular mass (P = 0.007). pI, hydrophobicity, and affinity of the glycopeptide for the pentapeptide target were not as important for activity. This suggested that a block of access of the antibiotic to its target could be the major factor determining activity. Outer membrane proteins of the vancomycin-susceptible mutant, resistant parent, and revertant strains appeared normal. The mutant exhibited increased susceptibility to both erythromycin and fusidic acid which was lost in single-step revertants to vancomycin resistance. Polymyxin B nonapeptide was synergistic with erythromycin and fusidic acid against the parent and revertant but not against the susceptible mutant. Analysis of the susceptibilities of control strains of E. coli and Salmonella typhimurium with known defects in lipopolysaccharide (LPS) synthesis revealed that core LPS mutants (Re chemotype) were phenotypically similar to the E. coli mutant under study. However, the LPS core of the mutant migrated slightly less rapidly on sodium dodecyl sulfate-polyacrylamide gel electrophoresis than wild-type or revertant core LPS and did not resemble Re chemotype LPS core obtained from Salmonella rfaC and rfaD mutants. These data suggest that defects in LPS core structure other than loss of heptose moieties may also be important in loss of resistance to large, hydrophilic molecules such as glycopeptides.

Anti-Bacterial Agents↗
PubMed1989

Inducible, transferable resistance to vancomycin in Enterococcus faecalis A256.

A strain of Enterococcus faecalis (A256) was isolated from the urine of a patient with urinary sepsis and was found to exhibit susceptibilities (micrograms per milliliter) to various glycopeptides as follows: vancomycin, 256; teicoplanin, 16; 62208, 512; 62211, 4; and 62476, 16. As judged by growth rates before and after exposure to sub-MICs of glycopeptides, vancomycin and 62476 induced self-resistance, 62208 and 62211 induced slight self-resistance, and teicoplanin did not induce self-resistance. Vancomycin induced cross-resistance to all other glycopeptides tested, as judged both in growth experiments and by direct measurement of inhibition of peptidoglycan synthesis in cells exposed to sub-MICs of vancomycin. Thus, the spectra of activity of the glycopeptides were not correlated with their patterns of induction. There was a correlation between the increased synthesis of a 39-kilodalton (kDa) protein located in the cytoplasmic membrane and the induction of resistance. Protoplasts of A256 were susceptible to inhibition of peptidoglycan synthesis by vancomycin at levels similar to those for susceptible strains. Vancomycin resistance was transferable on filters from the parent strain to E. faecalis JH2-2 at a frequency of about 10(-7), and the 39-kDa protein was also inducible by glycopeptides in these transconjugants. We conclude that A256 is resistant to glycopeptides by virtue of the synthesis of a 39-kDa cytoplasmic membrane protein, that this protein is probably involved in preventing access of the glycopeptides to their peptidoglycan targets, and that this resistance is transferable, probably by conjugation.

Bacterial Outer Membrane Proteins↗
PubMed1989

Serious infectious complications of corticosteroid therapy for COPD.

We report seven elderly patients with COPD who developed serious infectious complications during prolonged treatment with high doses of corticosteroids. Infections included invasive pulmonary aspergillosis, Herpes simplex stomatitis and esophagitis, cytomegalovirus pneumonia, bacterial sepsis, fungemia and meningitis due to Cryptococcus neoformans. Each of the three patients who developed invasive aspergillus pneumonia died. The efficacy of prolonged therapy with high doses of corticosteroids in patients with COPD is not proven. These cases illustrate the potential for serious infections in patients with COPD treated with corticosteroids.

Aged↗
PubMed1988

Introduction of a plasmid encoding the OHIO-1 beta-lactamase to an intermediate care ward by patient transfer.

A prospective study of 147 intermediate care ward (ICW) patients for acquisition of gentamicin-resistant Enterobacteriaceae (GRE) was carried out. Fifty (34%) were colonized or infected with one or more strains of GRE. Fifteen of these patients and one nurse were colonized with 22 strains (including ten species) of GRE bearing identical 60 kb plasmids encoding a novel beta-lactamase determinant, OHIO-1 and ANT(2"). Analysis of the time course of colonized patients on the ICW revealed one probable episode of cross-transmission. Five colonized patients had been residing in the ICW from one to four months prior to study initiation. Eight patients were admitted to the ICW from other hospital areas already colonized and one additional patient acquired colonization on the ICW from an unknown source. Thus, eight of ten patients admitted to the ICW during the prospective study were already colonized on admission to the ICW. To control this level of colonization it would therefore be necessary to direct efforts at limiting admission of colonized patients or attempting to eliminate the strain from persistently colonized patients, rather than trying to limit transmission within the ward.

Bacteriological Techniques↗
PubMed1988

The epidemiology of gentamicin-resistant Pseudomonas aeruginosa on an intermediate care unit.

The authors conducted a prospective six-month study of colonization by gentamicin-resistant Pseudomonas aeruginosa on an intermediate care unit at a Cleveland, Ohio hospital with the use of selective culture techniques, serotyping, and plasmid analysis. Thirty-five of 163 patients (21%) were culture positive at least once for gentamicin-resistant Pseudomonas aeruginosa. Patient samples, environmental cultures, and personnel hand cultures revealed no common source for the organisms. Plasmid profiling added little to the serotyping data. Only nonambulation and length of stay on the unit were significant independent risk factors for colonization with gentamicin-resistant Pseudomonas aeruginosa by multiple logistic regression analysis. Age, use of urinary catheters, exposure to antibiotics, and duration of antibiotic use were correlated with one or both of the independent risk factors, but were not themselves independently associated with colonization by these resistant organisms. Cross-colonization apparently was not an important mode of dissemination of gentamicin-resistant Pseudomonas aeruginosa on this intermediate care unit. The identified risk factors appear to be more important than cross-colonization, and control strategies should address these issues.

Adult↗
PubMed1987

Streptococcus mitis. A cause of serious infection in adults.

Twenty strains of Streptococcus mitis were isolated from blood or body fluids at the Cleveland Veterans Administration Medical Center from Jan 1, 1981, to April 30, 1984. Fifteen (75%) isolates were considered contaminants. Five (25%) were clinically important and associated with a serious infection of the oropharynx or gastrointestinal tract (three of five), endovascular system (one of five), or a prosthetic hip. Four of five patients required surgical intervention for treatment. Two of five died; one death was directly attributable to S mitis infection. Eighteen strains were available for detailed bacteriologic study. Three strains had a minimum inhibitory concentration of greater than 0.1 micrograms/mL of penicillin and six other strains were tolerant to penicillin. This review suggests that S mitis can be an important pathogen in adults and may cause infections other than endocarditis.

Adult↗
PubMed1987

Factors that influence the evolution of beta-lactam resistance in beta-lactamase-inducible strains of Enterobacter cloacae and Pseudomonas aeruginosa.

Induction ratios were determined for beta-lactamase-inducible strains of Enterobacter cloacae and Pseudomonas aeruginosa by using 10 beta-lactam agents. For E. cloacae, pre-incubation with ceftriaxone, cefoxitin, cefamandole, cefoperazone, or imipenem produced significantly larger amounts of beta-lactamase than did pre-incubation with moxalactam, clavulanate, ceftazidime, or aztreonam. For P. aeruginosa, imipenem was the best inducer, whereas ceftriaxone, piperacillin, cefoperazone, cefamandole, clavulanate, and aztreonam were poor beta-lactamase inducers. The rate of emergence of resistance by E. cloacae p99 and P. aeruginosa ATCC 27853 did not correlate with the induction ratio of the selecting agent; however, a strong correlation was noted between the mutation rate and the ratio of the MIC to the concentration of selecting antibiotic used. Emergence of resistance is related to the MIC of the antibiotic and the concentration of antibiotic used to select for resistance and is independent of the efficacy of the beta-lactam inducer. Resistant mutants arise through both beta-lactamase-dependent and -independent mechanisms.

Anti-Bacterial Agents↗
PubMed1987

Serious infections caused by Bacillus species.

Thirty-eight patients with serious infections caused by organisms belonging to the genus Bacillus are described. Our experience, and that reported in the literature, indicates that, in most cases, isolated Bacillus bacteremia is not a particularly serious disease. Therefore, under most circumstances, empiric antibiotic therapy designed specifically for treatment of Bacillus is probably not necessary. Endocarditis can occur, but apparently follows bacteremia only infrequently. When these bacteria cause localized infection such as pneumonia, pan-ophthalmitis, visceral abscess, or musculoskeletal infections, tissue necrosis and profound morbidity are the rule. The frequency of these complications following bacteremia appears to be low but cannot be estimated from our experience or that reported in the literature reviewed. The role of intravascular devices and trauma as predisposing factors is emphasized. Immunocompromised hosts and intravenous drug abusers appear predisposed, but intravascular devices in the former group may play an important role in the pathogenesis of Bacillus infections. Antibiotics which appear especially useful in the treatment of Bacillus infections are clindamycin and vancomycin, to which the vast majority of strains are susceptible in vitro. Beta-lactam antibiotics, including the new cephalosporins and penicillins, are of little value in this setting.

Adult↗
PubMed1987

Molecular epidemiology of OHIO-1 beta-lactamase.

A total of 31 plasmids, all bearing a gene that encodes a novel, plasmid-mediated Richmond-Sykes class III beta-lactamase designated OHIO-1 and a gene that encodes aminoglycoside 2"-adenyltransferase, have been collected from hospitals in Ohio. By using restriction endonuclease digestion and Southern hybridization, we were able to demonstrate that all these plasmids have a common genetic origin.

Bacteria↗
PubMed1987

Diagnosis of nosocomial pneumonia in intubated, intensive care unit patients.

The clinical distinction between bacterial colonization of the tracheobronchial tree and nosocomial pneumonia is difficult, especially in intubated patients. We studied 51 intubated, intensive care unit patients prospectively by serial examinations of tracheal aspirates for elastin fibers, graded Gram's stains, and quantitative bacterial cultures in conjunction with clinical and radiologic observations in an attempt to develop criteria for the early detection of pulmonary infection. Patients with infection had new or progressive pulmonary infiltrates plus 1 of the following: positive blood culture results, radiographic evidence of cavitation, or histologic evidence of pneumonia, or 2 or more of the following: new fever, new leukocytosis, or grossly purulent tracheal aspirates. Twenty-one patients developed infection, 22 remained colonized, and 8 had an uncertain status. Infiltrates developed in 34 patients (21 infected, 8 colonized, 5 uncertain status). Gram-negative bacilli were most commonly isolated and were more frequent in infected patients (81 versus 47%, p less than 0.05); Pseudomonas aeruginosa and Serratia marcescens were most often associated with infection. No differences were observed between infected and colonized patients in demographic features, smoking history, underlying disease, previous antibiotic therapy, days in hospital before intubation, preexisting pneumonia upon intubation, or highest temperature or leukocyte count during course. By univariate analysis, infected patients had a longer duration of intubation (p less than 0.05), higher Gram's stain grading for neutrophils (p less than 0.05) or bacteria (p less than 0.005), higher bacterial colony counts (p less than 0.05), and more frequent detection of elastin fibers in tracheal aspirates (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1987

Nosocomial clonal dissemination of methicillin-resistant Staphylococcus aureus. Elucidation by plasmid analysis.

An outbreak of methicillin sodium-resistant Staphylococcus aureus (MRSA) infection and colonization, mainly centered in the vascular surgery service, occurred in a 1000-bed tertiary care center between December 1983 and December 1984. Methicillin-resistant S aureus isolated before and during the outbreak was studied by both bacteriophage typing and by restriction endonuclease digestion of bacterial plasmid DNA. Bacteriophage typing was discrepant in nine (56%) of the 17 repeated analyses compared with one (3.4%) of the 29 for plasmid profiling. These typing methods revealed that the epidemic strain was introduced to the hospital from the community 15 months before the outbreak. The outbreak was caused by cross-transmission of the epidemic strain by health care personnel and was controlled by treatment of colonized personnel, education of personnel, and institution of barrier precautions for colonized or infected patients. Plasmid profiling with restriction endonuclease digestion was easier, more rapid, and more specific than bacteriophage typing in the evaluation of this outbreak.

Cross Infection↗
PubMed1987

Serratial bacteremia in the surgical patient.

A 42-month review has identified 32 surgical patients that had 45 episodes of Serratia marcescens bacteremia. Patients were identified in many surgical specialties. The primary focuses of infection were the urinary tract, intravascular devices, sputum, and soft tissue. In five patients, no focus was identifiable. Nine patients had polymicrobial sepsis with other bacteria or Candida. Of 41 isolates studied, five were resistant to all antibiotics that were commercially available. Only 76 per cent were sensitive to amikacin, 63 per cent to gentamicin, and 46 per cent to tobramycin. Statistically fewer patients died when an aminoglycoside and an expanded-spectrum penicillin were used in combination. The 44 per cent mortality rate of this group of patients indicates that environmental control, behavioral modification of health care professionals, and a more rationale use of broad-spectrum antibiotics are necessary to prevent this morbid complication.

Aged↗
PubMed1986

Gentamicin-resistance plasmids in an intensive care unit.

To better understand the role of plasmids and their importance in the endemic antibiotic resistance of Enterobacteriaceae, we began a prospective study of our combined medical intensive care/coronary care unit. An initial culture survey of the patients, ward staff, and environment was followed by a prospective sampling of 139 consecutive new admissions at the time of admission to the unit, and at regular intervals thereafter for the remainder of their stay. All cultures were planted on agar-containing gentamicin. Of the 147 patients studied, 12 (8.2%) were colonized with 20 strains of gentamicin-resistant gram-negative bacilli (GRGNB) at 29 sites. An additional four GRGNB were isolated from the environment. Of the 24 GRGNB strains, 7 (29%) Enterobacteriaceae carried plasmids shown to carry the gentamicin-resistance determinant. Plasmids were further characterized by restriction endonuclease digestion profiles of plasmid DNA purified from E. coli C600 transconjugants or transformants. A 93 kb plasmid introduced to the unit by a Serratia liquefaciens colonizing a patient transferred from another area in the hospital was identical to 93 kb plasmids carried by a C. amalonaticus and an E. aerogenes subsequently colonizing another patient on the unit. A 60 kb plasmid, first isolated from a S. marcescens colonizing a sink drain was later isolated from an E. cloacae colonizing a patient. Our results indicate that spread of specific R-plasmids may be one mechanism for dissemination of antibiotic resistance on our MICU/CCU.

Drug Resistance, Microbial↗
PubMed1986

Dissemination of a plasmid determining multiple antibiotic resistance between two Veterans Administration Medical Centers.

The endemic R-plasmids mediating resistance to gentamicin and multiple other antibiotics among many species of Enterobacteriaceae from the Minneapolis and Cleveland Veterans Administration Medical Centers were compared by restriction endonuclease digestion profiling and by phenotype expressed in sensitive E. coli recipients. Southern hybridizations were also performed. Our data indicate that these plasmids demonstrate some microheterogeneity, but are very closely related. Both are self-transferable and mediate resistance to ampicillin, carbenicillin, chloramphenicol, gentamicin, tobramycin, neomycin and kanamycin. These results suggest the dissemination of a conjugal R-plasmid or of Enterobacteriaceae bearing the plasmid between two midwestern Veterans Administration Medical Centers. The most likely mechanism of transmission may be the frequent transfer of patients between midwestern Veterans Administration Medical Centers.

Drug Resistance, Microbial↗
PubMed1986

Prevalence of colonization with antibiotic resistant gram-negative bacilli in a nursing home care unit: the importance of cross-colonization as documented by plasmid analysis.

A prevalence study was carried out on a 100-bed Veterans Administration nursing home care unit to determine the extent of colonization with gentamicin-resistant gram-negative bacilli (GRGNB). Hand cultures of 12 employees and 17 environmental cultures were negative. Twenty-six of 86 (30%) patients were colonized with 49 GRGNB. Sixteen patients (19%) had urinary colonization. Multivariate analysis revealed significant associations between rectal or perineal colonization (P less than 0.01), and the presence of a urinary device (82% condom catheters) (P less than 0.05), with urinary colonization. The most common isolates were Providencia stuartii (20), Escherichia coli (nine) and Klebsiella pneumoniae (nine). Twenty-six of 49 isolates carried plasmids. Restriction endonuclease digestion of plasmid DNA was performed for 21. Cross-colonization, as defined by the presence of the identical species with the identical restriction endonuclease digestion profile of purified plasmid DNA found in different patients, was observed for eight of 21 (38%) strains. All were geographically clustered. No strains could transfer gentamicin-resistance by conjugation and only two plasmids could transform our E coli recipient to gentamicin resistance. One E coli plasmid was identical to two Citrobacter freundii plasmids and a P stuartii plasmid isolated from three different patients. This 105 kb plasmid is conjugative and encodes resistance to ampicillin, carbenicillin, tetracycline, and sulfonamides. Thus, 57% of strains were cross-colonizing or contained identical R-plasmids. Southern hybridization using a 1 kb TEM-1 gene probe demonstrated sequences homologous to this probe in five of five nursing home plasmids examined.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗