Piperacillin is a new semisynthetic penicillin which is similar in structure to carbenicillin and ticarcillin. Since the latter antibiotics have been shown to cause abnormalities in hemostasis, we studied the effects of piperacillin on blood coagulation and platelet function. Fifteen healthy volunteers received the drug in doses of either 100, 200, or 300 mg/kg per day for a period of 7 days. Serial studies showed no abnormalities in blood coagulation in any subject. Decreased platelet aggregation responses to adenosine diphosphate, epinephrine, collagen, and arachidonic acid were commonly noted, but prolongation of the bleeding time occurred in only 3 of 15 subjects after 7 days of piperacillin administration. These results suggest that although piperacillin also induces platelet dysfunction, these effects may be less than those caused by ticarcillin or carbenicillin at an equivalent dosage.

Controversy persists concerning the role of early surgical intervention in severe infective endocarditis (IE). We therefore reviewed 163 episodes of well-documented IE in which 32 cardiac operations were performed during the active phase of IE. Congestive heart failure (CHF) was the principal indication for surgery in 88% (28/32); systemic emboli, 1/32; and persisting sepsis, 3/32. Staphylococcus and enterococcus were the most common infecting organisms in the operative group (44% and 16% respectively). Surgical mortality (11/32,37%) did not differ (p greater than 0.05) from medical mortality (26/131,20%). All 11 operative deaths occurred in patients moribund prior to surgery, including three with preoperative cardiac arrest. Surgical patients undergoing preoperative cardiac catheterization demonstrated marked CHF: a mean left ventricular end-diastolic pressure of 25.3 mm Hg. The mean cardiac index in 8/11 surgical deaths was lower (p less than 0.05) vs surgical survivors: 2.21/min/m2 vs. 3.21/min/m2. Postoperative complications were rare in the 21 surgical survivors. There were no episodes of continued infection, prosthetic dehiscence, or advanced heart block; only one paravalvular leak; and one systemic embolus. These findings emphasize the high medical and surgical mortality in patients with IE, suggest that delayed operative intervention may be a major causative factor resulting in a high surgical mortality, and justify an aggressive surgical approach in patients with valve dysfunction and heart failure. These data indicate that survivors of surgical intervention during active IE have eradication of infection and few postoperative complications.

We investigated the effects of apalcillin on blood coagulation and platelet function. The drug was administered to 21 human volunteers in daily intravenous doses of 75, 150, and 225 mg/kg. These doses evoked abnormalities in platelet aggregation similar to those found with piperacillin and mezlocillin and less striking than those produced by carbenicillin and ticarcillin. Plasma coagulation as measured by prothrombin time, activated partial thromboplastin time, thrombin time, and fibrinogen concentration was not affected. There were consistent and major reductions in plasma antithrombin III activity, particularly at the two higher dose levels. Of 21 patients, 7 (33%) also manifested maculopapular skin rashes which resolved after discontinuation of the drug.Penicillin and its semisynthetic antibiotic derivatives may affect hemostasis by causing a time-and dose-related defect in platelet aggregation (3, 9). The resultant platelet functional abnormality is most easily demonstrated in vitro by reduced aggregation to an ADP stimulus and in vivo by prolongation of the template bleeding time (7). Severity of the hemostatic defect is variable, however, and seems more predictable and profound with carbenicillin and ticarcillin, for example, than with piperacillin, mezlocillin, and ampicillin (2-4, 6, 7, 9). Apalcillin is a new semisynthetic penicillin with an extended antibacterial spectrum. It is structurally related to ampicillin. We administered apalcillin to normal human volunteers to assess its effects on hemostasis.MATERIALS AND METHODS Subjects. A total of 21 normal, healthy human volunteers (15 males, 6 females), ranging in age from 22 to 34 years (mean age, 24 years), entered Medical Center Del Oro Hospital in Houston, Texas, where the study was done. Initial evaluation included a history and physical examination to exclude anyone with evidence of peptic ulcer disease, gastrointestinal bleeding, renal disease, or penicillin allergy. Also performed were complete blood count, blood chemistries, urinalysis, electrocardiogram, and stool examination for occult blood. Each volunteer provided informed consent.Drug administration. Apalcillin (Wyeth Laboratories, Philadelphia, Pa.) was reconstituted to the desired concentration and then diluted in 100 ml of 5% dextrose in water and infused intravenously every 8 h. The volunteers were divided into three groups of seven. The volunteers received apalcillin daily at a dose of 75 (group A), 150 (group B), or 225 (group C) mg/kg for a 7-day period.Coagulation studies. Blood coagulation and platelet function were evaluated upon initiation of the study, and the evaluation was repeated on days 4, 7, and 14 after the start of antibiotic infusion. Platelet count, prothrombin time, activated partial thromboplastin time, thrombin time, and template bleeding time (Simplate; General Diagnostics, Div. Warner-Lambert Co., Morris Plains, N.J.) followed standard methodology (7). Platelet aggregation was measured in a PAP-3 aggregometer (Bio/Data Corp., Horsham, Pa.). Aggregation was induce...

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