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Histoplasma capsulatum is a dimorphic fungal zoopathogen of worldwide distribution that produces a broad spectrum of disease activity . In most cases the portal of entry is the lung, where inhaled spores and mycelial fragments of the fungus lodge within the terminal bronchioles and alveoli. Here, transition from the mycelial phase to the yeast phase ensues, presumably over a period of hours to days. The mycelial to yeast phase conversion is critical since it is the yeast form of H. capsulatum (Hc)' that is responsible for the pathogenesis of histoplasmosis in nearly all of its clinical manifestations (1) .The earliest pulmonary lesions induced by He yeasts in man and experimental animals are patches of pneumonitis consisting largely of parasitized macrophages (MO) (2-4) . He yeasts are thought to be phagocytized by resident pulmonary Mo within which they multiply with a generation time of -9-11 h (5) . Host Mep appear to be destroyed by the multiplying yeast forms that in turn, are phagocytosed by other Mo attracted to the infected site . The multiplication cycle is repeated within these cells and He yeasts are disseminated from the lung to other organs by the lympho-hematogenous route. In most cases, the primary lesions in lung and those at peripheral sites begin to resolve after development of measurable delayed-type hypersensitivity to antigens of He at 10-20 d after inoculation.During an early phase of infection, MO bind to and phagocytose He yeasts, thereby providing a highly permissive intracellular environment for multiplication of the organism. Later, however, after the activation of cell-mediated immune defenses, He yeasts that are bound and ingested by Mo appear to be inhibited or killed . To better understand the crucial process of initial recognition and attachment of He yeasts by phagocytic cells, we have studied the receptorligand interactions between unopsonized He yeasts and human MO derived from peripheral blood monocytes (PBM) of nommmune donors .

Kinetics of gentamicin inactivation by carbenicillin and ticarcillin were studied in vitro and in 17 patients with renal failure. In vitro, the half-life of carbenicillin in human serum at 37 C is longer (19.2 ± 0.7 h) than ticarcillin (7.2 ± 0.6 h). Thus, incubation of gentamicin with equal concentrations of ticarcillin or carbenicillin results in greater inactivation of aminoglycoside activity by the latter. If concentrations of the two penicillins are held equal by repetitive addition, rates of gentamicin inactivation are the same.The serum half-life of gentamicin in patients serving as their own controls was significantly reduced by administration of either penicillin. After carbenicillin, the half-life decreased from 46 ± 8 h to 22 ± 3 h (P < 0.02). The constant for inactivation of gentamicin (ks) by carbenicillin was 0.02 h-1. The results indicate that gentamicin requirements are underestimated by methods currently employed to calculate dosage for patients with renal failure who receive carbenicillin concurrently. Adjustment of gentamicin dosage in such cases by application of the ki for gentamicin is suggested.The antibiotic combination of an aminoglycoside and a penicillin or cephalosporin is frequently administered to provide broad antibacterial therapy for patients with sepsis. In particular, the combination of gentamicin and carbenicillin is employed for treatment of infections caused by Pseudomonas aeruginosa. Although clinical proof is lacking for the superiority of combined over single agent therapy in these infections, the simultaneous use of both antibiotics is favored by many clinicians (2).Most, if not all, penicillins have the capacity to inactivate gentamicin in vitro at a rate that is dependent upon temperature, concentration, and medium composition (20,22). The reaction is thought to occur via nucleophilic opening of the (&lactam ring, probably by the methylamino group ofgentamicin with concomitant formation ofa biologically inactive amide (3, 27; P. G. Daniels, personal communication). As a rule, penicillins must be present for several hours in concentrations at least fivefold greater than those of gentamicin before inactivation of the latter can be demonstrated (20).In clinical practice, such inactivation is observed most frequently when gentamicin and a penicillin are inadvertently mixed in the same bottle of parenteral solution, which is then hung for slow intravenous (i.v.) infusion. Ofthe penicillins administered concurrently with gentamicin, carbenicillin is most frequently given in sufficient dosage to achieve peak serum levels of at least 100 ,ug/ml, thereby exceeding concentrations of the aminoglycoside by more than fivefold. Nevertheless, little or no destruction of aminoglycoside activity can be demonstrated in patients with normal renal function if the two antibiotics are given by separate routes. In patients with renal failure, however, the serum half-lives (t112) of gentamicin and carbenicillin are greatly prolonged (13,28). Thus, repetitive administration of carbenicillin to...

Teicoplanin is a new glycopeptide antibiotic structurally related to vancomycin and ristocetin. Like vancomycin, it is highly active in vitro against a wide spectrum of grampositive organisms, including enterococci and both methicillin-susceptible and methicillin-resistant staphylococci (3,14,21). Unlike vancomycin, however, teicoplanin has a long elimination half-life permitting administration once a day (11,20,21), and it is well tolerated when given intramuscularly (i.m.), with a bioavailability of 90% (21)

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