Guidelines for the treatment of acidaemia with THAM.

THAM (trometamol; tris-hydroxymethyl aminomethane) is a biologically inert amino alcohol of low toxicity, which buffers carbon dioxide and acids in vitro and in vivo. At 37 degrees C, the pK (the pH at which the weak conjugate acid or base in the solution is 50% ionised) of THAM is 7.8, making it a more effective buffer than bicarbonate in the physiological range of blood pH. THAM is a proton acceptor with a stoichiometric equivalence of titrating 1 proton per molecule. In vivo, THAM supplements the buffering capacity of the blood bicarbonate system, accepting a proton, generating bicarbonate and decreasing the partial pressure of carbon dioxide in arterial blood (paCO2). It rapidly distributes through the extracellular space and slowly penetrates the intracellular space, except for erythrocytes and hepatocytes, and it is excreted by the kidney in its protonated form at a rate that slightly exceeds creatinine clearance. Unlike bicarbonate, which requires an open system for carbon dioxide elimination in order to exert its buffering effect, THAM is effective in a closed or semiclosed system, and maintains its buffering power in the presence of hypothermia. THAM rapidly restores pH and acid-base regulation in acidaemia caused by carbon dioxide retention or metabolic acid accumulation, which have the potential to impair organ function. Tissue irritation and venous thrombosis at the site of administration occurs with THAM base (pH 10.4) administered through a peripheral or umbilical vein: THAM acetate 0.3 mol/L (pH 8.6) is well tolerated, does not cause tissue or venous irritation and is the only formulation available in the US. In large doses, THAM may induce respiratory depression and hypoglycaemia, which will require ventilatory assistance and glucose administration. The initial loading dose of THAM acetate 0.3 mol/L in the treatment of acidaemia may be estimated as follows: THAM (ml of 0.3 mol/L solution) = lean body-weight (kg) x base deficit (mmol/L). The maximum daily dose is 15 mmol/kg for an adult (3.5L of a 0.3 mol/L solution in a 70kg patient). When disturbances result in severe hypercapnic or metabolic acidaemia, which overwhelms the capacity of normal pH homeostatic mechanisms (pH < or = 7.20), the use of THAM within a 'therapeutic window' is an effective therapy. It may restore the pH of the internal milieu, thus permitting the homeostatic mechanisms of acid-base regulation to assume their normal function. In the treatment of respiratory failure, THAM has been used in conjunction with hypothermia and controlled hypercapnia. Other indications are diabetic or renal acidosis, salicylate or barbiturate intoxication, and increased intracranial pressure associated with cerebral trauma. THAM is also used in cardioplegic solutions, during liver transplantation and for chemolysis of renal calculi. THAM administration must follow established guidelines, along with concurrent monitoring of acid-base status (blood gas analysis), ventilation, and plasma electrolytes and glucose.

Contemporary issues in the management of pediatric infections.

BACKGROUND: Pediatric infections still pose numerous challenges, and expert guidance is needed on many current issues including diagnostic methods and the optimal choice and duration of therapy. OBJECTIVES: To highlight areas of current concern and controversy and to provide some pointers to factors affecting the choice of antibiotic therapy. DISCUSSION: Most community-acquired pediatric infections are diagnosed on clinical grounds. Treatment is initiated on an empiric basis; microbiologic diagnosis is usual only for urinary tract infections and tonsillitis. The choice of the most appropriate antibiotic agent for ambulatory treatment depends on antimicrobial activity and pharmacokinetic parameters as well as on compliance-enhancing features such as once daily dosing, good tolerability and the acceptability of the pediatric formulation. The newer oral cephalosporins such as ceftibuten have a favorable combination of properties including excellent clinical efficacy and are increasingly being used in preference to penicillins. Although clinical cure is regarded as the "gold standard" in the evaluation of therapy, the importance of bacterial eradication must also be emphasized.

[Structural changes in clinical pediatrics with special reference to small departments (author's transl)]. / Strukturwandel der klinischen Pädiatrie Unter besonderer Berücksichtigung "kleiner Abteilungen".

Changing facts and developments in clinical pediatrics in Germany during the past years have been analysed and discussed. Facts which altered the quantity and quality of clinical pediatrics are demonstrated by own observations, and informations collected from all pediatric departments in the FRG and West-Berlin. The need for sufficient numbers of staff to meet with the changing and intensified tasks of clinical pediatrics is emphasized.

[Right and wrong ways to treat meningitis (author's transl)]. / Wege und Irrwege der Meningitis-Therapie.

A brief survey of the last 200 years of diagnosing and treating meningitis is followed by a critical analysis and comparison of therapeutic results since the introduction of effective chemotherapy 44 years ago. This reveals nearly as good results during the early years as compared to nowadays. Modern age and pathogen dependent therapeutic regimes are discussed and valued. New ways of therapy are not yet generally necessary for the common causes of bacterial meningitis in childhood. The increasing resistance of some strains of H. influenzae or pneumococci, however, will necessitate the development of new antibiotics. Own experience and results in treating 76 patients with purulent meningitis are reported and compared with the literature, where pathogen or therapy dependent mortality is welldocumented but detailed data on follow-up studies are sporse.

[Therapy of pediatric infections with cefixime]. / Therapie pädiatrischer Infektionen mit Cefixim.

In a pilot study with a limited number of patients the efficacy and tolerance of cefixime, a new oral cephalosporin antibiotic, were investigated in 15 children with the clinical diagnosis of bacterial respiratory tract infection, otitis media or urinary tract infection. The dosage was 2 x 4 mg/kg body weight daily for a period of seven to 11 days. Clinical efficacy was good in 13 cases, and subjective tolerance was good in all cases. The results support the assumption that cefixime is suited for the treatment of children with bacterial infections of the airways and urinary tract with sensitive pathogens.

Cefotaxime monotherapy of bacterial meningitis caused by gram-positive pathogens.

Primary meningitis in children is caused by two gram-negative bacterial species, Neisseria meningitidis and Haemophilus influenzae, and one gram-positive bacterial species Streptococcus pneumoniae. Despite optimal penicillin susceptibility, with few exceptions, therapeutic results in pneumococcal meningitis are by far worse than with the other two pathogens. Therefore, and because of the detection of penicillin-resistant rods, the study of alternatives in therapy is justified and was started with cefotaxime. Including six of our own patients, there are reports on 87 patients in the literature suffering from S. pneumoniae meningitis who were treated with cefotaxime monotherapy. Results of these studies will be analyzed. As none of these patients belonged to a prospective controlled study group, final evaluation in comparison with penicillin therapy remains open. There are also several reports on successful treatment of group B streptococcus meningitis with cefotaxime, although there is no need to abandon penicillin therapy. Staphylococcus aureus and Staphylococcus epidermidis meningitis, usually secondary in shunted hydrocephalus, brain tumors, brain injury or other causes, should not be treated with cefotaxime because of its limited activity on these bacteria. Listeria monocytogenes and Streptococcus faecalis are primarily cefotaxime-resistant, and neonatal meningitis of unknown origin, therefore, should not be treated with cefotaxime alone as long as these pathogens cannot be excluded.

[Cefotaxime monotherapy in bacterial meningitis in childhood]. / Cefotaxim Monotherapie der bakteriellen Meningitis im Kindesalter.

Bacterial meningitis in 20 children was treated with cefotaxime. 17 children received this antibiotic throughout the disease as monotherapy, three were changed to Penicillin G (2) or ampicillin (1), after sensitivity of the pathogen was known, although cefotaxime had been effective. All bacterial isolates were highly susceptible to cefotaxime. All CSF cultures were sterile at second tap, performed 24 to 48 hrs after therapy was started. Cefotaxime and desacetyl-cefotaxime concentrations in CSF, measured by HPLC in 9 patients were in the range of 4 to 34 (average 17.6) mg/l and 2.1 to 82 (average: 15.1) mg/l, representing a CSF-serum ratio of 8 to 74% (average 45.6%) for cefotaxime and 25 to 151% (average: 73.7%) for desacetyl-cefotaxime. Clinical outcome was favourable in 17 patients. There were one death and late neurological deficits in three. Cefotaxime monotherapy is recommended instead of standard therapy with chloramphenicol and/or ampicillin because of superior antibacterial activity, lower toxicity and lesser side-effects for primary meningitis in children caused by N. meningitides, S. pneumoniae, or H. influenzae type b.

[Efficiency of diagnostic procedures in clinical pediatrics (author's transl)]. / Die Effektivität diagnostischer Massnahmen in der klinischen Pädiatrie.

Diagnostic procedures were evaluated in a prospective study including 1099 unselected children seen at a children's hospital. The predominant importance of a detailed case history (88,3%) and of the clinical examination could be demonstrated. On the other hand, apparative routine examinations were of very limited value, mostly to exclude particular diagnoses. The efficiency of apparative diagnostic procedures could be improved by allowing for a more differentiated indication of their use.

[Cefotaxim--an alternative in the treatment of purulent meningitis in children?]. / Cefotaxim--eine Alternative zur Behandlung der eitrigen Meningitis im Kindesalter?

Cefotaxim was administered to ten children with purulent meningitis. All isolated micro-organisms were highly sensitive to it in serial dilution, except for one case, and were quickly removed from blood and CSF by the administration of cefotaxim alone. Blood and CSF concentrations measured in eight children were much above the minimal inhibitory concentration for the particular micro-organism. Thus cefotaxim has a high antibacterial activity and satisfactory CSF passage in purulent meningitis caused by sensitive, especially gram-negative, bacteria and is well suitable for therapy, if penicillins alone or combined are not applicable or effective.