Renal adaptation to phosphorus deprivation: characterization of early events.

Renal adaptation to low dietary phosphorus (P) can occur within 4 h. To characterize events preceding adaptation, rats were gavaged with 0.6% P (+P) or 0.03% P (-P) diet and killed 1, 2, or 4 h later. Brush border membrane vesicles were prepared and Na-dependent phosphate (Pi), glucose, and 1-proline transport were measured. In intact rats, 1 h after gavage, serum P in +P was 8.0 +/- 0.5 and in -P, 6.1 +/- 0.4 mg/dl, p less than 0.01. One and 2 h after gavage, Pi uptake was similar between groups; at 4 h, 0.25 min Pi uptake was increased by 59.3% +/- 14.8 in -P, p less than 0.02, n = 11. In thyroparathyroidectomized rats, Pi uptake increased in -P by 40.1% +/- 7.4 compared to +P at 2.5 h after gavage, and by 51.3 +/- 9.3 at 4 h, p less than 0.025, n = 11. When actinomycin D or cycloheximide were administered both 16 h prior to and at gavage, 0.25 min Pi uptake 4 h after gavage was 59.1% +/- 14 and 60.6% +/- 19 higher in -P than +P, respectively, p less than 0.025. The adaptation was detected only when measured with an inward-directed Na-gradient. Na-dependent glucose and proline uptakes were not changed by -P diet. These studies demonstrate that early renal adaptation to low dietary P is preceded by a fall in serum P, is independent of parathyroid hormone, and does not require protein synthesis. Early adaptation may represent an increased rate of carrier movement or a change in availability of already synthesized carrier. The signal for adaptation may be the decrease in serum P, or filtered load of phosphorus.

In vitro activity of newer beta-lactam agents in combination with amikacin against Pseudomonas aeruginosa, Klebsiella pneumoniae, and Serratia marcescens.

The in vitro activity of cefoperazone, ceftazidime, ceftizoxime, moxalactam, and N-formimidoyl thienamycin was evaluated alone and in combination with amikacin to assess possible synergistic activity against isolates of amikacin-resistant Pseudomonas aeruginosa and multidrug-resistant Serratia marcescens and Klebsiella pneumoniae susceptible to amikacin (one S. marcescens isolate was also resistant to amikacin). The checkerboard agar dilution method was used. Ceftazidime and thienamycin followed by moxalactam and cefoperazone were the most active agents versus the P. aeruginosa alone and in combination testing. Ceftazidime, moxalactam, and thienamycin showed the greatest activity against S. marcescens, and all agents except cefoperazone were active against K. pneumoniae. The finding of synergy or partial synergy in combination testing was found in the majority with all three genera, including levels below the breakpoint for both amikacin and the beta-lactam agents. This wide in vitro activity indicates that clinical evaluation of these agents in treatment of multidrug-resistant infections is warranted.

Susceptibility of Legionella spp. to mycinamicin I and II and other macrolide antibiotics: effects of media composition and origin of organisms.

Thirty-three strains of Legionella spp., 29 of which were L. pneumophila, were tested for their susceptibilities to erythromycin (EM), rosaramicin, tylosin, mycinamicin I (Sch-27897), and mycinamicin II (Sch-27896). Testing was performed using an agar dilution method with two different types of media: buffered charcoal yeast extract medium supplemented with 0.1% alpha-ketoglutarate (BCYE alpha) and filter-sterilized yeast extract medium with 0.1% alpha-ketoglutarate (BYE alpha). The minimal inhibitory concentrations (MICs) of the drugs tested relative to the MICs of erythromycin were: rosaramicin, MIC approximately equal to 0.2 EM MIC; tylosin, MIC approximately equal to 2 EM MIC; mycinamicin I, MIC approximately equal to 0.5 EM MIC; and mycinamicin II, MIC approximately equal to EM MIC. Both types of media caused equivalent partial inactivation of the macrolides which was apparently due entirely to pH effect. MICs on BCYE alpha were one to five times more than those observed on BYE alpha; this may be due to poorer growth on BYE alpha.

In vitro susceptibility of cephalothin-resistant Enterobacteriaceae and Pseudomonas aeruginosa to Amikacin and selected new beta-lactam agents.

Amikacin was evaluated in vitro by agar dilution testing against 148 different clinical isolates of cephalothin-resistant Enterobacteriaceae and Pseudomonas aeruginosa in parallel with cephalothin, cefoxitin, moxalactam, N-formimidoyl thienamycin, ceftriaxone, and cefmenoxime. Cefsulodin was also evaluated against 39 isolates of P. aeruginosa. More than 80% of all isolates tested were also gentamicin resistant, as determined by disk testing. Moxalactam and amikacin had comparable high activities against Proteus species, Escherichia coli, Serratia species, and Providencia species, and both amikacin and N-formimidoyl thienamycin had comparably high activities against the Klebsiella-Enterobacter group. N-Formimidoyl thienamycin was the most active agent against P. aeruginosa, followed by cefsulodin and amikacin.

Clinical and laboratory studies of nosocomial Staphylococcus aureus resistant to methicillin and aminoglycosides.

A methicillin/aminoglycoside-resistant strain of Staphylococcus aureus (MARS) was likely introduced by transfer of a patient from another hospital. Over the next year, 20 other patients were colonized or infected with MARS of the same phage type, although antibiograms varied. Affected patients usually had serious underlying disease and were in intensive care units. Vancomycin therapy was frequently delayed and MARS may have contributed to the death of some patients. The mode of spread was not definitively delineated, but two nurses were found to be colonized. Institution of isolation procedures was difficult, but the problem gradually waned. Susceptibility testing showed vancomycin to be the most active agent. Synergy studies showed no consistent effect of combining methicillin with an aminoglycoside. This experience illustrates the problem of MARS spread between hospitals and wards, the need for institution of effective control measures, and consideration of early empiric use of vancomycin.