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Biomedical subjects

A L Baltch

Publications and source records attributed to A L Baltch.

At least 73 records · Page 4Linked to original sources

Serotyping of 1,458 pneumococcal isolates with analysis of bacteremia in 84 patients.

During a 61-month period, 1,458 pneumococcal isolates (including 87 bacteremia strains) were collected at the Albany Veterans Administration Medical Center and serotyped with the use of the typing system of the New York Department of Health Laboratories. Fifty percent of all isolates were of types in the 14-valent vaccine, while 68% were in 23-valent vaccine. Types 3, 6, 9, and 34 were the most prevalent types. Sixty-two percent of blood isolates were of types in the 14-valent vaccine, while 77% were in the 23-valent vaccine. Fifty-six percent of bacteremias were nosocomial and 44% were community acquired with a fatality rate of 41% and 18%, respectively. The fatality rate was greatest with risk factors such as asplenia and azotemia. These data support the recommendation for the use of 23-valent pneumococcal polysaccharide vaccine in high-risk patients, especially those who might acquire bacteremia in a nosocomial setting.

Adult↗

In vitro activity of CI-934 and other antimicrobial agents against gram-positive and gram-negative bacteria.

The activity of CI-934, a new carboxy-quinolone antibiotic, against gram-positive cocci and bacilli and gram-negative bacilli was compared with that of reference antibiotics. CI-934 demonstrated excellent activity against gram-positive organisms, including Corynebacterium sp. In addition, although the activity of CI-934 against gram-negative bacilli was less than that reported for similar agents, it was comparable to that of aminoglycosidic aminocyclitol antibiotics.

Anti-Bacterial Agents↗

Combinations of antibiotics against Pseudomonas aeruginosa.

Pseudomonas aeruginosa continues to cause serious infections, especially bacteremias, in hospitalized and immunocompromised patients. During the past 10 years, bacteremia due to this organism has increased in frequency in many institutions, and mortality rates in patients with rapidly fatal disease remain as high as 85 percent despite antibiotic therapy. Available data do not allow firm conclusions regarding the in vivo predictive value of in vitro synergy testing for P. aeruginosa, but in vitro demonstration of synergy appears important in selecting therapy for patients with P. aeruginosa infections. Combinations of aminoglycosides (amikacin or tobramycin) with highly active antipseudomonal beta-lactam antibiotics are most likely to be associated with in vitro synergy. Experimental studies in animals models support the use of combination therapy for local and bacteremic infections. Similarly, the retrospective and prospective studies in humans suggest better survival with combinations of antimicrobials, usually including aminoglycosides and beta-lactams, in immunocompromised hosts. At present, the use of newer penicillins, piperacillin, azlocillin, or selected antipseudomonal cephalosporins, in combination with amikacin or tobramycin, appears to be the preferable antimicrobial therapy for serious P. aeruginosa infections.

Aminoglycosides↗

Effects of Pseudomonas aeruginosa cytotoxin on human serum and granulocytes and their microbicidal, phagocytic, and chemotactic functions.

The effect of Pseudomonas aeruginosa cytotoxin on human granulocytes (PMNs) and pooled human serum was studied by hemacytometer counts, phagocytic, bactericidal, and chemotaxis assays, and by transmission electron microscopy. The optimal assay conditions for phagocytosis of 75Se-labeled P. aeruginosa 1348A included 20% pooled human serum and a ratio of one PMN to between 10 and 20 bacteria. For the bactericidal assay, 20% pooled human serum and a ratio of one PMN to between one and five bacteria were used. Chemotaxis of PMNs was studied by agarose gel technique with 10(-7) M f-Met-Leu-Phe or 0.01 to 35 micrograms of cytotoxin per ml as a chemoattractant. The degree of PMN destruction was dependent on cytotoxin concentrations and PMN exposure time to cytotoxin. Virtually complete PMN lysis was observed after a 2-h exposure to 6 to 10 micrograms of cytotoxin per ml. PMN exposure to 2 micrograms of cytotoxin per ml for as long as 2 h had no adverse effect on phagocytosis. PMN exposure to greater than or equal to 4 micrograms of cytotoxin per ml for 2 h demonstrated a significant decrease in the percentage of bacteria killed. The results of experiments designed to separate cytotoxin effect on PMN lysis from the effect on PMN bactericidal capacity showed that there is an effect of cytotoxin on PMN bactericidal function. PMN exposure to 4 micrograms of cytotoxin per ml for 30 min caused a significant decrease in PMN migration. Cytotoxin had no chemoattractant qualities or effect on pooled human serum as studied by chemotaxis and phagocytosis assays. Although a cytotoxin concentration of greater than or equal to 2 micrograms/ml was required to demonstrate PMN ultrastructural changes observed in transmission electron microscopy studies, at a concentration of 0.1 microgram/ml, cytotoxin caused an impairment in the integrity of the PMN membrane, allowing a low-molecular-weight substance (ruthenium red) to enter into the cytoplasm. Cytotoxin may be an important factor in the pathogenesis and in the high mortality rate of patients with P. aeruginosa infections.

Bacterial Toxins↗

Human plasma fibronectin effect on serum-mediated uptake of Pseudomonas aeruginosa PA 1348A by human granulocytes.

The effect of human plasma fibronectin on human granulocyte (PMN) phagocytosis of one strain of Pseudomonas aeruginosa (PA 1348A) was examined in a previously defined optimal phagocytic assay. Normal and fibronectin-deficient serum demonstrated similar rates of bacterial uptake by PMNs. Complement depletion of both sera inhibited phagocytosis. Addition of purified fibronectin did not alter phagocytosis. These findings strongly support the conclusion that fibronectin neither promotes nor inhibits opsonization for phagocytosis of this strain of P. aeruginosa.

Blood Bactericidal Activity↗

A prevalence survey of infections in a combined acute and long-term care hospital.

A prevalence survey of infections among 572 acute and long-term care patients in the Albany Veterans Administration Medical Center was conducted in September 1979. Presence of infection was determined by patient examination and chart review. Urine specimens from 94% of patients were cultured. The total number of clinically significant infections was 178; 117 were nosocomial (20.5 per 100 patients). The prevalence rate of nosocomial infections was highest on the Intermediate Service (long-term medical care) followed by the Surgical and Medical Services. Sites with the highest nosocomial infection rates were urinary tract (10.7), skin and subcutaneous tissues (5.1), and surgical wounds (3.0) per 100 patients. Nosocomial infections increased with age and length of hospital stay which partially explained the higher rate on the Intermediate Service. Patients using condom drainage and Foley catheters showed similarly high rates of bacteriuria. Antimicrobial drug use was 17% for acute care patients and 4% for long-term and psychiatry patients. Excepting Providencia stuartii urinary tract infection confined to the Intermediate Service, the bacterial isolates and their antibiotic susceptibilities were similar for the acute and long-term care services.

Adult↗

Pharmacokinetics of moxalactam in elderly subjects.

The pharmacokinetics of moxalactam were studied in 19 male volunteers 60 years of age or older with normal liver function tests and a creatinine clearance of greater than or equal to 60 ml/min. Moxalactam was administered in single or multiple intravenous or intramuscular doses. Rapid and complete intramuscular bioavailability was demonstrated in a subgroup of the study population. The mean plasma half-life was 2.9 +/- 0.8 h for intravenous doses and 3.5 +/- 0.9 h for intramuscular doses. Average renal clearances of 0.04 liters/kg per h accounted for 74.0 +/- 15.0% of total plasma clearance. Moxalactam plasma clearance showed a statistically significant (P less than 0.01) correlation with measured and calculated creatinine clearance. The major differences in moxalactam pharmacokinetics seen in the elderly appear to be related to diminishing renal function and highly variable nonrenal elimination. Creatinine clearance can be used in estimating moxalactam doses in the elderly without significant renal impairment, but recommendations for the use of serum creatinine as an estimation of renal function or drug half-life are not valid in this population group.

Aged↗

In vitro comparison of Pseudomonas aeruginosa isolates with various susceptibilities to aminoglycosides and ten beta-lactam antibiotics.

Susceptibilities of 98 clinical isolates of Pseudomonas aeruginosa, including 33 strains with known mechanisms of amikacin resistance, were tested by the agar dilution method against 10 beta-lactam drugs. Ceftazidime, imipenem, and cefsulodin had the greatest activity, regardless of the aminoglycoside susceptibilities. The strains which were highly resistant to amikacin appeared to be less susceptible to some beta-lactam drugs, especially if their resistance was related to amikacin-inactivating enzymes; statistical significance, however, was observed for aztreonam only.

Aminoglycosides↗

Comparative in vitro activities of enoxacin (CI-919, AT-2266) and eleven antipseudomonal agents against aminoglycoside-susceptible and -resistant Pseudomonas aeruginosa strains.

The in vitro activity of enoxacin (CI 919, AT 2266), a new oral quinolone carboxylic acid compound, was compared with those of gentamicin, tobramycin, amikacin, azlocillin, piperacillin, aztreonam, moxalactam, imipenem, cefsulodin, ceftazidime, and cefoperazone against 101 aminoglycoside-susceptible and 105 aminoglycoside-resistant Pseudomonas aeruginosa strains. Among these 206 P. aeruginosa isolates were 25 strains with known mechanisms of resistance to amikacin. The activity of enoxacin was similar to that of tobramycin against aminoglycoside-susceptible strains, with MICs of 1.0 to 2.0 micrograms/ml and 0.5 to 1.0 microgram/ml, respectively, for 90% of the strains. Enoxacin was the most active agent in this in vitro study against aminoglycoside-resistant P. aeruginosa strains, with MICs of 2.0 to 4.0 micrograms/ml for 90% of the strains. Strains with enzymatic resistance to amikacin were more resistant to beta-lactams (except enoxacin and imipenem) than were strains with decreased permeability.

Aminoglycosides↗

Effect of aztreonam in combination with azlocillin or piperacillin on Pseudomonas aeruginosa.

Aztreonam, a synthetic monobactam antimicrobial agent specifically active against aerobic, gram-negative microorganisms, was studied in combination with the extended-spectrum penicillins azlocillin and piperacillin against 46 strains of Pseudomonas aeruginosa. Of these strains, 4.3% were synergistically inhibited, and 19.7% showed evidence for an additive effect of the antibiotics. All other strains showed indifference. The addition of cefoxitin to these combinations increased the MICs of azlocillin and piperacillin by two to three tubes, whereas zero- to one-tube increases were noted for aztreonam MICs. Attempts to block cefoxitin-induced beta-lactamase production by using clindamycin were unsuccessful even at high clindamycin concentrations.

Anti-Bacterial Agents↗

Effect of Pseudomonas aeruginosa cytotoxin on thymidine incorporation by murine splenocytes.

The interaction of highly purified Pseudomonas aeruginosa cytotoxin (PAC) with murine splenocytes was examined. Added at culture initiation, PAC (0.1 to 0.5 microgram/ml) inhibited subsequent [3H]deoxythymidine incorporation measured between 42 to 48 h. Incorporation of [3H]deoxythymidine was inhibited 50% in lipopolysaccharide-, phytohemagglutinin-, and concanavalin A-stimulated cultures by 0.20, 0.32, and 0.39 microgram of PAC per ml, respectively. It is concluded that PAC exhibits a narrow inhibitory concentration response range of 0.1 to 0.5 microgram/ml which, secondarily, is affected by the presence of mitogens. Antitoxin added at splenocyte culture initiation, directly after PAC, yielded greater than or equal to 86% protection against PAC inhibition of [3H]deoxythymidine incorporation. Addition of antitoxin to cultures at different times after PAC demonstrated a time-dependent loss of antitoxin protective effect over a 12-h period, indicating that PAC became cell associated and refractory to antitoxin within this time period. PAC preincubated with splenocytes at 4 degrees C for less than or equal to 1 h could not be removed by washing of cells and was fully inhibitory to [3H]deoxythymidine incorporation when these cells were cultured at 37 degrees C. This finding was confirmed by demonstrating that 125I-labeled PAC bound immediately to cells. It is concluded that PAC action on splenocytes is dose- and time-dependent and consists of a two-phase process: (i) a very rapid binding of PAC to the cell surface available to antitoxin, and (ii) a slower toxicity development phase of ca. 12 h, during which PAC becomes refractory to antitoxin.

Animals↗

Inhibitory and bactericidal activities of amifloxacin, a new quinolone carboxylic acid, compared with those of seven other antimicrobial agents.

The activity of amifloxacin, a new quinolone carboxylic acid compound, against 147 strains of microorganisms was studied and was compared with the activities of cinoxacin, trimethoprim, amikacin, and four beta-lactam antimicrobials. The minimal concentration at which 90% of strains were inhibited by amifloxacin was lowest for Escherichia coli and Klebsiella sp (less than or equal to 0.125 microgram/ml), followed by Proteus sp (less than or equal to 0.25 microgram/ml), Enterobacter sp and Citrobacter sp (less than or equal to 0.5 microgram/ml), Providencia sp (less than or equal to 2 micrograms/ml), and Pseudomonas aeruginosa, Serratia sp, and Acinetobacter calcoaceticus var anitratus (less than or equal to 8 micrograms/ml). When compared with the ranges of activity of seven reference antimicrobials, the range of amifloxacin activity was lowest for P aeruginosa, Citrobacter sp, Proteus sp, and A calcoaceticus var anitratus and similar to aztreonam's activity against Enterobacter sp. For amikacin-resistant P aeruginosa, the minimal inhibitory concentrations (MICs) of amifloxacin ranged from 1 to 16 micrograms/ml. The MICs and minimal bactericidal concentrations (MBCs) of amifloxacin were similar. For all strains tested, microbial susceptibilities to amifloxacin were greater than those to currently available oral antimicrobial drugs, such as cinoxacin and trimethoprim.

Anti-Bacterial Agents↗

Bacteremia due to Pseudomonas aeruginosa: use of a combined typing system in an eight-year study.

P aeruginosa bacteremia is a nosocomial disease with a high mortality occurring in colonized, debilitated, and leukopenic patients and in those receiving immunosuppressive and antimicrobial agents [2]. Outbreaks of P aeruginosa bacteremia have often been associated with environmental reservoirs [3]. The 190 strains of P aeruginosa described in this study represent single isolates from bacteremic patients during an eight-year period. Representing about 50% of total isolates, the most common pyocin types were 1b, 3, and 10, immunotypes 1, 2, and 3 + 7, and serotypes 11, 6, and 1. Of the 37 known pyocin types, only 10 were represented in this study. All seven immunotypes and 14 of 17 serotypes were found. The overall typability for each of the three techniques was 88%-90%; however, the largest numbers of typable patterns were found when all three typing methods or pyocin and either immunotyping or serotyping were used. The smallest number of typing patterns occurred when immunotyping and serotyping were performed together. Correlation among the following types was greater than 50%; pyo 3:immuno 1:sero 6; pyo 10:immuno 2:sero 11, and pyo NI:immuno 4:sero 1. Upon repeated testing the reproducibility of types for each technique was 98%-100%. For the most precise epidemiologic studies of P aeruginosa infections all three typing methods should be employed.

Humans↗

Moxalactam concentrations in human prostatic tissue.

The concentrations of moxalactam in human prostatic tissue, obtained by enucleation or transurethral resection, were measured in 10 patients after the intramuscular administration of two 500-mg doses. The average concentrations of moxalactam in prostatic tissue in the enucleated and transurethral resection specimens were 4.0 micrograms/g and 5.2 micrograms/ml, and the ratios of the moxalactam concentrations in prostate to those in plasma were 0.24 and 0.31, respectively. The concentrations of moxalactam achieved in prostatic tissue after the administration of relatively low doses were greater than the minimum inhibitory concentrations of moxalactam for most common gram-negative pathogens. Concentrations of moxalactam in carefully obtained transurethral resection specimens were similar to those found in the enucleated specimens.

Aged↗

Bacteremia following dental cleaning in patients with and without penicillin prophylaxis.

The rate, type, and magnitude of bacteremia were studied in 56 patients undergoing dental cleaning with and without penicillin prophylaxis. Sixty-one percent of patients without penicillin prophylaxis were bacteremic 5 minutes following the procedure. Although a significant decrease in detectable bacteremia occurred in patients receiving penicillin prophylaxis, the recovery of streptococci was not significantly different in the two groups. Using the present sample of patients as a basis for statistical inference, the true rate of bacteremia in such patients could be between 41% and 79% with 95% certainty. The magnitude of bacteremia was low and positive quantitative pour plates occurred at 5 minutes and only in patients without penicillin prophylaxis. Of the 71 total bacterial isolates, 53 (74.6%) were anaerobes and 18 (25.4%) were aerobes. This study indicates that parenteral penicillin prophylaxis for dental cleaning decreased detectable bacteremia rates significantly and could be recommended for patients with valvular heart disease who are known to be vulnerable to endocarditis.

Adult↗

In vitro comparison of N-formimidoyl thienamycin (MK0787) and Azlocillin with three aminoglycosides and ticarcillin against Pseudomonas aeruginosa.

The activities of N-formimidoyl thienamycin and azlocillin were compared with those of tobramycin, gentamicin, amikacin, and ticarcillin against 175 Pseudomonas aeruginosa isolates, including 24 strains with known mechanisms of resistance to aminoglycosides. The 50% mean inhibitory concentration for azlocillin was lower than for ticarcillin, but the 90% mean inhibitory concentration was similar for both drugs. All susceptible and multidrug-resistant strains were susceptible to N-formimidoyl thienamycin.

Amikacin↗