In vitro susceptibilities of Rickettsia and Bartonella spp. to 14-hydroxy-clarithromycin as determined by immunofluorescent antibody analysis of infected vero cell monolayers.

The in vitro susceptibilities of Rickettsia akari, Rickettsia conorii, Rickettsia prowazekii, Rickettsia rickettsii, Bartonella elizabethae, Bartonella henselae and Bartonella quintana to different concentrations of clarithromycin, 14-hydroxy-clarithromycin (the primary metabolite of clarithromycin) and tetracycline in Vero cell cultures, were determined by enumeration of immunofluorescently-stained bacilli. The extent of antibiotic-induced inhibition of foci was recorded for each dilution of antibiotic and compared with an antibiotic-negative control. Based upon MIC data, clarithromycin alone is highly active against all three Bartonella spp., R. akari and R. prowazekii, while 14-hydroxy-clarithromycin is active against R. conorii, R. prowazekii and R. rickettsii. Further testing is warranted in animal models and human clinical trials, to examine the activity of both clarithromycin and its primary metabolite and to define further the role of clarithromycin in therapy, particularly of infections caused by obligate intracellular bacteria such as Rickettsia and Bartonella spp.

Dobutamine: ten years later.

Dobutamine is a commonly used positive inotrope for the short-term management of heart failure. It is commercially available as a 50:50 mixture of two isomers with unique effects on alpha- and beta adrenergic receptors. In dosages of 2-15 micrograms/kg/minute, dobutamine has been shown to increase cardiac output (mainly through stroke volume), reduce systemic vascular resistance, lower central venous and pulmonary artery wedge pressures, improve renal blood flow, and relieve signs and symptoms of congestive heart failure. At higher dosages it can increase heart rate and induce arrhythmias. Recent evidence indicates that effects of dobutamine last long after the drug has been eliminated from the plasma, and some work has been done on ambulatory use of this agent. Dobutamine has been used successfully in several circumstances, such as after cardiac surgery, in patients with myocardial infarction, and in various shock states. An understanding of the pathophysiology of the underlying disorder is important in deciding which catecholamine to use. With this in mind, monotherapy or combination therapy with inodilators such as dobutamine, or inopressors like dopamine will follow logically.

Dobutamine in elderly septic shock patients refractory to dopamine.

The hemodynamic effects of dobutamine (2.5-20 micrograms/kg per min) were studied in six elderly patients with septic shock which was refractory to dopamine (15 micrograms/kg per min). Dobutamine infusion resulted in significant increases in cardiac index (CI), stroke index (SI) and left ventricular stroke work index (LVSWI) and similar declines in heart rate (HR), mean pulmonary artery pressure (MPAP), pulmonary capillary wedge pressure (PCWP), systemic vascular resistance (SVR) and total pulmonary resistance (TPR). Dose response curves demonstrated a linear rise in CI with increasing doses of dobutamine and parallel decreases in HR and PCWP. MAP was unchanged. These data indicate that dobutamine may be a useful adjunct to dopamine therapy in the management of elderly patients with septic shock.

Acute posttraumatic acalculous cholecystitis.

A series of 18 patients who had acute posttraumatic acalculous cholecystitis over a 12 year period was presented. An attempt was made to determine the etiologic factors involved in the pathogenesis of the disease. Large amounts of parenteral narcotics administered over a prolonged period were evident in all patients. Narcotic-induced biliary stasis appeared to be the prime factor involved in the genesis of acalculous cholecystitis after trauma. Other factors such as the presence of shock, respiratory failure, acute renal failure, parenteral hyperalimentation, and multiple transfusions were less prevalent and were not temporally related to the onset of the disease.

Cutaneous blisters and carbon monoxide poisoning.

We present the cases of three patients with skin blisters following carbon monoxide (CO) poisoning. Their blisters appeared to be related to the severity of the poisoning (HbCO levels of more than 40%). Two of the three patients died despite aggressive initial 100% surface oxygen followed by hyperbaric oxygen therapy. The pathophysiology of this type of blister remains unresolved. It could result from pressure necrosis alone or from a combination of pressure necrosis and direct CO inhibition of tissue oxidative enzymes. Although skin involvement as a result of CO poisoning is less frequently reported today than in the past (perhaps because of misidentified burns or because of more aggressive resuscitation and treatment protocols), the physician should recognize that such blisters may signal severe CO poisoning.

Chromium intake and urinary chromium excretion of trauma patients.

Glucose metabolism is altered after trauma and those factors that affect glucose metabolism often affect chromium (Cr) metabolism and excretion. To ascertain whether urinary Cr excretion is affected by the elevated serum glucose and other factors associated with trauma, the serum glucose and urinary Cr and Creatinine (Cre) excretion of seven severely traumatized patients were determined. The Cr concentration of intravenous (IV) fluids administered was determined and approximate Cr intake calculated. For all patients, urinary Cr concentration was high in the initial sample collected within 24 h of admission (10.3 ± 2.5 ng/mL, mean ± SEM) and decreased significantly (P < 0.05) by 42 h (2.0 ±0.6 ng/mL). The mean urinary Cr concentration 42 h following admission was 10 times greater than the urinary Cr concentration of normal, healthy subjects (0.2 ± 0.02 ng/mL). There was no significant change in urinary Cre concentration within 42 h of admission, therefore the ratio of urinary Cr to Cre (ng Cr:mg Cre) also decreased. Serum glucose concentration was elevated at admission (170 ± 18 mg/dL, mean ± SD) and decreased to 145 ± 10 mg/dL by 48 h post-admission. The intravenous fluids, dextrose and NaCl, were the lowest in Cr of the samples tested, range 0.02 to 0.20 ng/mL; lactated Ringer's solution, with or without dextrose, contained 10-20 times more Cr and plasma protein fraction contained approximately 32 ng/mL. The mean calculated Cr intake for the first 24 h postadmission was 37.1 µg/d, significantly greater (P < 0.01) than intake from 24 to 48 h (0.12 µg/d) and 48-72 h (1.63 µg/d). The IV intake of Cr varied for trauma patients depending on fluids required during treatment, but for all patients the relatively high IV Cr intake was rapidly excreted in the urine. These data demonstrate that urinary Cr concentration is elevated several-fold within 24 h of trauma and that Cr contents of intravenous fluids administered in the days immediately following injury vary dramatically. The effects of trauma alone on Cr excretion are difficult to assess because of the variable intake of Cr from IV fluids.

Efficacy of hetastarch in the resuscitation of patients with multisystem trauma and shock.

A prospective trial of 6% hetastarch (HES) v 5% plasma protein fraction (PPF) as the colloid component of intravenous (IV) fluid resuscitation was conducted in 32 patients with multisystem trauma and/or hemorrhagic shock. Patient age, mechanism and pattern of injury, and IV fluid requirements were similar in both groups. No intergroup differences were noted in indexes of hepatic, pulmonary, or renal function or in the incidence of infection. The frequency of other complications, including bleeding diatheses, and mortality were identical in the two groups. Although this investigation should be viewed as a pilot study, our results suggest that, compared with PPF, HES in large volumes is a safe, effective colloid solution in the resuscitation of patients with multisystem trauma and/or hemorrhagic shock. Further study of HES in a larger number of patients is warranted by these findings.

Predicting serum gentamicin levels in adult trauma patients.

A one-compartment, open-linear, pharmacokinetic model for gentamicin dosing has been developed at the Maryland Institute for Emergency Medical Service Systems (MIEMSS). The model was used to predict both the gentamicin dose required to achieve desired peak and trough serum concentrations and the peak and trough serum concentrations that would result from administering empirically chosen doses. This model was tested in 31 patients, aged 15 to 82 years (mean 39.3 +/- 17.7 years), whose creatinine clearance (CCI) ranged from 12 ml/min to 197 ml/min (mean 106.9 +/- 53.1 ml/min). The predictions of the dosage model were compared with the measured peak and trough serum concentrations in these patients. The predicted peak serum levels correlated highly with the measured peak serum levels (r 0.97). The mean difference (+/- SD) between the predicted and measured peak levels was 0.28 +/- 0.22 mu g/ml. The predicted trough serum levels correlated well with the measured trough serum levels (r 0.91). The mean difference between the predicted and measured trough levels was -0.03 +/- 0.18 mu g/ml. This approach makes it possible for bactericidal levels of gentamicin to be maintained in patients with wide variations in stable renal function. Frequent serum gentamicin determinations are unnecessary. Requiring only an inexpensive calculator, the method has proved to be economical as well as clinically useful.

Teratogenic potential of some psychopharmacologic drugs: a brief review.

The placenta has been considered a protective barrier between the mother and fetus. Because many drugs pass relatively freely between mother and fetus, the possible causal relationship between drug ingestion and the incidence of birth defects in humans demands critical examination. A brief review of background information about this interaction and an overview of the effects of commonly used drugs are presented.