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Biomedical subjects

S M Markowitz

Publications and source records attributed to S M Markowitz.

At least 73 records · Page 4Linked to original sources

In vitro activity of cefoxitin, alone and in combination with aminoglycoside or other beta-lactam antibiotics against common gram-negative pathogens.

We examined 160 strains of Enterobacteriaceae and Pseudomonas aeruginosa for susceptibility to cefoxitin, aminoglycosides, and other beta-lactam antibiotics, alone and in combination. The aminoglycosides were the most effective agents tested, but, except for some strains, cefoxitin inhibited all organisms at a 90% minimal inhibitory concentration of 25 micrograms or less per ml. We observed a relatively high incidence of antagonism or nonsynergy when cefoxitin was tested in combination with other agents against 33 gentamicin-susceptible gram-negative bacilli. No synergy was observed when various combinations with cefoxitin were tested against three strains of cephalothin-resistant, carbenicillin-resistant Enterobacteriaceae of varying gentamicin susceptibility.

Aminoglycosides↗

Transferable tetracycline resistance in Clostridium difficile.

The transfer of tetracycline resistance among strains of Clostridium difficile is described. Transfer occurred by a conjugation-like event that was insensitive to deoxyribonuclease, could not be mediated by donor culture filtrates or chloroform-treated donor cultures, and required cell-to-cell contact. Tetracycline-resistant progeny recovered from matings displayed a resistance phenotype identical to that of the donor in level of resistance, constitutive expression, and transmissibility. Although the original tetracycline-resistant donor contained 5 x 10(6)- and 22 x 10(6)-dalton plasmids, standard physical analyses of antibiotic-resistant transconjugants revealed no plasmid deoxyribonucleic acid molecules in common with the donor strain. Furthermore, tetracycline-susceptible derivatives of the original donor always possessed a plasmid complement identical to that of the resistant parental strain as determined by restriction endonuclease digestion analysis. The results indicate that the tetracycline resistance determinant(s) was not encoded by readily detectable plasmid deoxyribonucleic acid and may be chromosomally located.

Clostridium↗

Cefazolin and moxalactam pharmacokinetics after simultaneous intravenous infusion.

A high-performance liquid chromatographic method for the measurement of moxalactam concentrations in serum was modified to permit the simultaneous measurement of both moxalactam and cefazolin. We then studied whether the simultaneous administration of both moxalactam and cefazolin to normal subjects would produce profiles of serum concentration versus time which were the same as those obtained after the administration of each drug individually. Six healthy adults received a 30-min infusion of cefazolin (10 mg/kg), followed in 2 days by the same dose of moxalactam. After 2 days, both antibiotics were administered together. A two-compartment model was found to adequately characterize the data, and the serum concentration curve for each drug when given alone was statistically identical to that obtained after simultaneous administration. Cefazolin was found to produce a significantly greater peak serum concentration (105 +/- 14 versus 81 +/- 21 microgram/ml) and a significantly greater area under the curve (218 +/- 42 versus 157 +/- 19 . microgram h/ml). The terminal half-life of moxalactam was not significantly longer than for cefazolin (2.2 +/- 0.6 versus 2.0 +/- 0.6 h, respectively). The method of simultaneous administration may have distinct advantages over conventional methods for studies of comparative tissue penetration.

Adult↗

Aminoglycoside predictions using a hand-held calculator: limitations of the model.

Previously published methods for determining an appropriate aminoglycoside dosage have been adapted for use in the hand-held programmable calculator (Texas Instrument-59). The purpose of this study was to evaluate the accuracy of calculator-generated serum level predictions compared with measured values. Twenty-four adult patients receiving intravenous aminoglycosides (gentamicin, netilmicin, or tobramycin) had urine and serum collected for creatinine clearance calculations and had blood obtained for peak and through aminoglycoside concentration determinations. All but one patient had normal renal function. A statistically significant relationship between predicated and measured creatinine clearance values was found. There was also generally good agreement between the calculator-predicted aminoglycoside levels and the measured levels, although some patients exhibited unexplained deviations. Error in the estimation of creatinine clearance and adjustments for lean body weight did not improve prediction accuracy. We conclude that the hand-held calculator was able to predict measured aminoglycoside levels for most patients with acceptable precision. However, the calculator method offers no real advantage over other methods (except speed in performing the calculation), and may give the user a false sense of security.

Aminoglycosides↗

Sequential outbreaks of infection due to Klebsiella pneumoniae in a neonatal intensive care unit: implication of a conjugative R plasmid.

Sequential outbreaks of infection in a neonatal intensive care unit were due to multiple antibiotic-resistant strains of Klebsiella pneumoniae of different serotypes. In investigations of these outbreaks, the transfer of resistance to gentamicin, ampicillin, cephalothin, carbenicillin, and kanamycin from gentamicin-resistant organisms to standard laboratory recipients and between recipients was observed. Purified plasmid DNA, isolated from all multiple antibiotic-resistant strains, was analyzed by agarose gel electrophoresis, which revealed a common, large plasmid component with a molecular size of 71 megadaltons. Analysis of drug-resistant progeny suggested this plasmid encoded resistance to antibiotics and the information needed for its transmission. The identity of the plasmid from three different sources was established by the use of restriction-enzyme fingerprinting. The dissemination and persistence of this plasmid in environmental and fecal organisms, despite the disappearance of multiple antibiotic-resistant K. pneumoniae, provided a potential source for spread to other bacteria.

DNA↗

Rocky Mountain spotted fever: diagnostic dilemma of the atypical presentation.

Two patients with Rocky Mountain spotted fever presented with atypical manifestations which led to a delay in diagnosis and treatment. Such clinical manifestations occurring in endemic areas during warm months should not eliminate consideration of the proper diagnosis. If RMSF cannot be ruled out, therapeutic regimens should include appropriate antimicrobial coverage.

Adolescent↗

Comparative susceptibilities of clinical isolates of Serratia marcescens to newer cephalosporins, alone and in combination with various aminoglycosides.

We examined 100 clinically significant isolates of Serratia marcescens for susceptibility to newer cephalosporin and cephamycin antibiotics, alone and in combination with various aminoglycosides. Moxalactam and cefotaxime were the most effective agents; all isolates were inhibited by 25 and 50 micrograms/ml, respectively. All strains were susceptible to amikacin at concentrations safely achievable in serum, whereas gentamicin, netilmicin, and tobramycin inhibited 63, 63, and 16% of the isolates, respectively. Moxalactam, cefotaxime, and amikacin were active against gentamicin-susceptible and gentamicin-resistant strains. Studies of synergy revealed that moxalactam and cefotaxime, in combination with netilmicin or amikacin, were often synergistic and infrequently antagonistic against cephalothin- and gentamicin-resistant strains. These results suggest that moxalactam and cefotaxime, alone or in combination, may be efficacious in treating infections due to multiply antibiotic-resistant S. marcescens.

Aminoglycosides↗

Therapeutic failures with miconazole.

A retrospective review of therapeutic failures of miconazole in three patients is presented. Miconazole, a new imidazole derivative, is a broad-spectrum antifungal agent purportedly effective topically, orally, and parenterally against a number of species of fungi. Three patients with the following culturally proven deep fungal infections were treated with miconazole: (i) destructive arthritis (Sporothrix schenckii), (ii) meningoencephalitis (Cryptococcus neoformans), and (iii) disseminated aspergillosis (Aspergillus fumigatus). All the organisms were susceptible in vitro to 1.56 mug or less of miconazole per ml using a broth dilution technique. In each patient, miconazole administered intravenously in dosages of 30 mg/kg per day failed to control or eradicate infection. Miconazole serum levels ranged from <0.5 to 4.35 mug/ml as determined by radial diffusion bioassay. Cerebrospinal fluid levels were virtually undetectable. In one patient (C. neoformans), miconazole was given intraventricularly in doses of 15 mg without response. Therapeutic failures were attributed to suboptimal body fluid levels of miconazole. The reason(s) for such low levels of activity was not clear, but may have been poor penetrance into tissues, in vitro inactivation, and/or unusually rapid excretion. Untoward reactions from miconazole included fever, chills, nausea, vomiting, and phlebitis.

Adult↗

R-factor inheritance and plasmid content in mucoid Pseudomonas aeruginosa.

Eighteen strains of alginate-producing mucoid Pseudomonas aeruginosa were evaluated with respect to plasmid content and the ability to maintain well-characterized R plasmids. The spontaneous loss of alginate production in these strains varied from 0.01 to 0.7% and was not significantly increased by plasmid curing regimens. Examination of cleared lysates of these strains and their isogenic nonmucoid derivatives by agarose gel electrophoresis failed to reveal plasmid DNA. R-plasmid (P-incompatibility-group) transfer to mucoid P. aeruginosa was unaffected by the presence of the alginate capsule. Maintenance and expression of such plasmids in the mucoid strains were confirmed by agarose gel electrophoresis and by verification of plasmid-linked drug resistance and pilus-specific bacteriophage sensitivity. These studies demonstrate that alginate production does not appear to be plasmid linked and that mucoid P. aeruginosa are capable of receiving and donating certain drug resistance plasmids. Since some of the plasmids used here have been shown to mobilize chromosomal DNA, strains constructed in this study should afford the means for exploring the genetic basis of the mucoid phenotype.

Alginates↗

Existence of Sporothrix schenckii as a pulmonary saprophyte.

A 48-year-old male custodian and part-time gardener was hospitalized for treatment of renal tuberculosis. Sputum cultures failed to reveal mycobacteria, but Sporothrix schenckii was isolated over an eight-month period. In the absence of clinical or roentgenographic evidence of active lung disease, we postulate the saprophytic existence of S schenckii in this patient's tracheobronchial tree. Recognition of this state would obviate the need for the commonly accepted therapy for pulmonary sporotrichosis, amphotericin B.

Humans↗

Experimental Acanthamoeba infections in mice pretreated with methylprednisolone or tetracycline.

Human infections due to free-living amebas of the genus Acathamoeba have been reported sporadically, occasionally in individuals with underlying diseases. To determine if such infections may be considered opportunistic, groups of laboratory mice were pretreated with either methylprednisolone or tetracycline and inoculated intranasally with 1.075 times 10(4) Acanthamoeba castellanii isolated from a natural fresh water well. Results were compared with controls receiving either drug or amebas alone and with controls receiving saline injections with and without amebas. The mortality rate for those animals receiving methylprednisolone and amebas (50%) was found to be greater than the mortality in ameba controls (10%) (P equal 0.074). Similarly, the mortality rate for animals receiving tetracycline and amebas (60%) was higher than the mortality in the ameba controls (10%) (P equal 0.0286). Precise mechanisms for the increased mortality were unknown but were suspected to be due to the capacity of either corticosteroids or tetracycline to suppress host defenses, particularly those depending on neutrophils. The findings suggest a potentially pathogenic role for naturally occurring Acanthamoeba sp in humans with depressed host immunity.

Amebiasis↗

Endocarditis due to accidental penetrating foreign bodies.

A 15 year old boy had an eight month history of recurrent fever, malaise and poor appetite. Chest roentgenogram revealed a foreign object overlying the right ventricle. Multiple blood cultures grew Enterobacter cloacae. The patients condition improved and blood cultures became negative following gentamicin and carbenicillin therapy. E. cloacae was isolated from the foreign body (a finishing nail) at surgery. Antimicrobial therapy was continued for a total of 30 days, and the patient made an uneventful recovery.

Adolescent↗

Experimental pneumonitis and encephalitis caused by acanthamoeba in mice: pathogenesis and ultrastructural features.

For a more precise definition of the clinicopathological features of experimental acanthamoebic infection in mice, trophozoites of Acanthamoeba castellanii and Acanthamoeba polyphaga were instilled intranasally into adult white mice. Eight to 20 days after inoculation, severe pulmonary disease developed; one to two days later, neurological signs ensued. On pathologic examination an amebic broncho-pneumonia associated with encephalitis was found. Trophozoites and cysts were seen in lung and brain. Although Naegleria is spread by the olfactory route, cerebral lesions produced by Acanthamoeba might result principally from hematogenous carriage from the lungs. Other differences between infections caused by Naegleria and those caused by Acanthamoeba in mice also exist and serve to emphasize that when natural infections with Acanthamoeba occur, a distinct clinicopathological entity may be produced.

Amebiasis↗