Netilmicin (Sch 20569), a semisynthetic aminoglycoside related to gentamicin C 1a , was evaluated in vitro in agar dilution testing against 224 different clinical isolates of gentamicin-resistant Enterobacteriaceae and Pseudomonas aeruginosa in parallel with amikacin, gentamicin, sisomicin, and tobramycin. Netilmicin showed a very high degree of activity against gentamicin-resistant organisms, but amikacin was more active in vitro, particularly against Providencia stuartii and P. aeruginosa . Sisomicin and tobramycin were consistently less active than either netilmicin or amikacin. Netilmicin was bactericidal in broth testing against P. aeruginosa . Netilmicin showed a greater difference between results with agar and broth dilution testing than did amikacin.

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% a-ketoglutarate (BCYEa) and filter-sterilized yeast extract medium with 0.1% a-ketoglutarate (BYEa). The minimal inhibitory concentrations (MICs) of the drugs tested relative to the MICs of erythromycin were: rosaramicin, MIC 0.2 EM MIC; tylosin, MIC 2 EM MIC; mycinamicin I, MIC 0.5 EM MIC; and mycinamicin II, MIC EM MIC. Both types of media caused equivalent partial inactivation of the macrolides which was apparently due entirely to pH effect. MICs on BCYEa were one to five times more than those observed on BYEa; this may be due to poorer growth on BYEa.The treatment of choice for Legionnaires disease and other Legionella sp. infections is erythromycin (10,12, 20). Mycinamicins are new macrolide antibiotics with antibacterial spectra similar to the spectrum of erythromycin (17). The purpose of this study was to determine whether two of the mycinamicin compounds had in vitro activity against Legionella sp. similar to other macrolide antibiotics (4,7,13,14,18). In addition, the effect of deletion of activated charcoal from the growth medium was determined, as it is known that charcoal yeast extract (CYE) medium inactivates many antimicrobial agents, including macrolides (4,7,14). This laboratory currently uses a filter-sterilized yeast extract medium without charcoal to test for pigment production of Legionella sp. (15). Since most recent clinical and environmental isolates of L. pneumophila grow readily on this medium, we felt that this medium could be used to grow Legionella sp. for susceptibility testing. Likewise, we felt that study of this charcoal-deleted medium could clarify whether charcoal was the interfering substance in CYE. Additional purposes were to study lower concentrations of rosaramicin than were previously tested (4) and to determine minimal inhibitory concentration (MIC) values on buffered CYE medium supplemented with a-ketoglutarate, since the addition of buffer and a-ketoglutarate to CYE medium dramatically improves the growth of L. pneumophila (3).MATERIALS AND METHODS Media. CYE medium buffered with N-[2-acetamido]-2-aminoethanesulfonic acid (ACES) buffer (Sigma Chemical Co.) and supplemented with 0.1% monopotassium a-ketoglutarate (BCYEa; Sigma Chemical Co.) was made as previously described (3). Buffered yeast extract medium supplemented with 0.1% monopotassium a-ketoglutarate (BYEa) was made with the same quantities of ingredients as for BCYEa except that the activated charcoal was deleted. Also, the yeast extract was filter sterilized with a 0.22-p.m filter (Millipore Corp.) rather than autoclaved; it was added to the autoclaved molten cooled buffer-agar-a-ketoglutarate base at 50°C. The filter-sterilized L-cysteine and ferric p...

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.

No abstract

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.