[Urine chemiluminescence in preclinical diagnosis of neonatal drug-induced nephropathy]. / Khemiliuminestsentsiia mochi v doklinicheskoi diagnostike neonatal'nykh lekarstvennykh nefropatii.

Animal experiments demonstrate that gentamycin, kanamycin and carbenicillin affect lipid peroxidation in the kidneys. This can be registered by chemiluminescence of renal and urinary homogenates. This phenomenon was also used in functional examination of the kidneys in 161 neonates treated by antibiotics. The earliest renal dysfunctions due to nephrotoxicity were detected by chemoluminescence induced by ions of bivalent iron. The method is simple and rapid, this making it convenient in neonatal practice for detection of nephropathy before the symptoms presentation.

Basic aspects related to penicillin-allergy skin testing: on the variability of the hapten-paratope interaction.

Ampicillin and benzylpenicillin conjugated to human serum albumin were used as immunogens in order to obtain antihaptenic IgG responses in outbred guinea pigs according to different schedules, all involving complete Freund's adjuvant. The individual responses were characterized by ELISA and by ELISA inhibition using ampicillin, benzylpenicillin, and carbenicillin peptidic conjugates for coating and for inhibition. In several instances, drastically reduced cross-reactivity and even its absence were observed, although the penicillin antigens differ only in the side-chain. The notion that the invariantly present thiazolidine ring will always provide significant binding to antibodies against all penicillins differing only in the side-chain has to be dropped. The experiments were performed in relation to newer findings of clinical penicillin-allergy skin testing which suggest that benzylpenicillin-based reagents alone are not able to detect or predict all reactions against semisynthetic penicillins. The experimental evidence here obtained corroborates this conclusion.

[The use of clindamycin and netilmicin for preventing postoperative wound infection in patients with cancer of the upper respiratory and digestive tracts]. / Primenenie klindamitsina i netilmitsina dlia profilaktiki posleoperatsionnoi ranevoi infektsii u bol'nykh rakom verkhnikh dykhatel'nykh i pishchevaritel'nykh putei.

Clindamycin (2.7 g/day) and netilmicin (5.6 mg/kg) were used for 6-10 days in 27 patients with laryngeal and oral cancer versus beta-lactam antibiotics and aminoglycosides received by 56 matched patients to prevent infection of the operative wound. Suppuration was observed in 11.1 and 41.4% of the patients, respectively (p < 0.05), the temperature rose over 38 degrees C in 22.2% and 42.9% of the patients, respectively (p < 0.05). The regimens showed similar toxicity. The findings proved high efficacy of clindamycin combination with netilmicin in infection prophylaxis in patients operated on for upper respiratory and digestive tract cancer.

Iatrogenia en neurología / Iatrogenesis in neurology

LAs iatrogenias más frecuentes en Neurología son: reacciones adversas y enfermedades inducidas por medicamentos, complicaciones de técnicas diagnósticas, complicaciones de procederes quirúrgicos y complicaciones de métodos terapéuticos (AU)

Adverse reactions to prolonged treatment with high doses of carbenicillin and ureidopenicillins.

Charts were reviewed for 63 patients whose chronic pseudomonas osteomyelitis was treated with high doses of extended-spectrum penicillins for prolonged periods. The incidence of untoward drug reactions was significantly higher than expected. Carbenicillin evoked adverse reactions in 22.8% of patients. However, most of these reactions were mild, and a change of drug was required in only 5.7% of cases. No adverse drug reactions were observed with cumulative doses of less than 750 g. In contrast to carbenicillin, the ureidopenicillins were associated with adverse reactions in 67.7% of patients; most reactions were moderate to severe in intensity; a cumulative dose of greater than 250 g produced adverse reactions; and discontinuation or change of therapy was required in 51.6% of cases. The main adverse reactions to both carbenicillin and the ureidopenicillins included rash, drug fever, leukopenia, eosinophilia, thrombocytopenia, and hepatic damage.

Comparative effects of mezlocillin and carbenicillin on platelet function and thromboxane generation in patients with cancer.

Carbenicillin and mezlocillin are widely used for treatment of Pseudomonas infections in patients with cancer. Carbenicillin has been reported to cause platelet dysfunction and bleeding diathesis in some individuals. We evaluated whether carbenicillin causes deterioration of platelet function in patients with cancer and whether mezlocillin causes similar effects on platelets from normal subjects or from patients with cancer. In these in vitro studies, carbenicillin and mezlocillin decreased ADP and epinephrine-induced platelet aggregation and thromboxane A2 generation similarly, but only in concentrations of 3.2 mg/ml or higher. In contrast, carbenicillin was more potent than mezlocillin in decreasing ristocetin-induced platelet aggregation. We also evaluated effects of these antibiotics on platelet function in 19 patients with cancer who developed fever and neutropenia. These patients received either mezlocillin (10 patients) or carbenicillin (nine patients) in combination with nafcillin and gentamycin. Neither carbenicillin nor mezlocillin had any significant effect on platelet aggregation or thromboxane A2 generation. Lack of effects in vivo was due to defective platelet function in these patients prior to any antibiotics. These defects were most probably related to underlying disease and/or prior chemotherapy. Thus, carbenicillin and mezlocillin can both safely be used in patients with cancer who develop fever and neutropenia, and neither seems to have advantage over the other in terms of platelet function.

Comparison of cefamandole and carbenicillin in preventing sepsis following penetrating abdominal trauma.

One hundred and five patients with penetrating abdominal injuries were treated with single-antibiotic regimens. Forty-seven patients were treated with intravenous (IV) cefamandole and for comparison 58 patients were treated with IV carbenicillin previously shown to be effective against postoperative infections associated with abdominal trauma. The overall incidence of deep infection on a single antibiotic therapy was 8.6 per cent, including two patients on cefamandole alone (4.3%) and seven (12.1%) on carbenicillin alone. One in each antibiotic group died of sepsis with a total mortality of 1.9 per cent. The authors concluded that cefamandole when used alone was found to be safe and more effective than carbenicillin alone in preventing sepsis in patients with abdominal trauma.

Ceftazidime compared with gentamicin and carbenicillin in patients with cystic fibrosis, pulmonary pseudomonas infection, and an exacerbation of respiratory symptoms. British Thoracic Society Research Committee.

An open randomised comparison of a new intravenous cephalosporin, ceftazidime, with the established regimen of gentamicin and carbenicillin was carried out in patients with cystic fibrosis who had persisting pulmonary infection with Pseudomonas species and who developed acute exacerbations of respiratory symptoms. Fifty patients received ceftazidime and 32 gentamicin and carbenicillin. The ceftazidime and gentamicin were given every eight hours and the carbenicillin every six hours. The mean total daily doses were 151 mg/kg for ceftazidime, 6.3 mg/kg for gentamicin and 450 mg/kg for carbenicillin. The mean duration of treatment was 10 days in patients receiving gentamicin and carbenicillin and 12 days in those receiving ceftazidime. Of the patients with pseudomonas in the initial sputum specimen in whom sputum was cultured after treatment, six (26%) of 23 receiving gentamicin and carbenicillin and seven (18%) of 39 receiving ceftazidime had sputum free from pseudomonas at the end of treatment, but recolonisation occurred subsequently. In those receiving ceftazidime all 10 coexisting organisms were eliminated, whereas only four of seven coexisting organisms in patients receiving gentamicin and carbenicillin were eliminated. Overall clinical improvement occurred in 25 (78%) of 32 patients treated with gentamicin and carbenicillin and 48 (96%) of 50 patients treated with ceftazidime. Nineteen (59%) of the patients receiving gentamicin and carbenicillin but only 15 (30%) of those receiving ceftazidime required admission to hospital or intravenous antibiotics, or both, or died during the three months after treatment. Side effects in both groups were similar, mild, and infrequent. Thrombophlebitis occurred in four patients treated with gentamicin and carbenicillin but in no patients treated with ceftazidime.

Sangrado postquirúrgico por carbenicilina / Postsurgical bleeding due to cabernicillin

Se presenta el caso de un adolescente de 14 años de edad que ingresó al hospital por fístula estercorácea como complicación de una apendicectomía. Diecinueve días después de su ingreso, se llevó a cabo la resección de la fístula sin complicaciones transquirúrgicas. Se administró carbenicilina a 400 mg/kg/día; dos horas después de la primera dosis, presentó sangrado masivo que ameritó reintervención encontrándose 500 ml de sangre libre en cavidad. Se demostró disfución plaquetaria. Se suspendió la carbenicilina y se manejó con plasma rico en plaquetas, con lo que se controló el episodio hemorrágico. Se discute la fisipatología y se revisa la literatura al respecto

Ticarcillin-induced cystitis. Cross-reactivity with related penicillins.

Two children had dysuria, sterile pyuria, and microscopic hematuria develop during treatment with ticarcillin disodium. With the exception of a predominance of pyuria over hematuria, the clinical course and laboratory findings in this disorder were similar to those observed in hemorrhagic cystitis, a potential complication of the use of several semisynthetic penicillins and penicillin G potassium. One patient had urinary abnormalities develop during two courses of ticarcillin therapy and subsequently after initiation of piperacillin sodium therapy. A second patient in whom hemorrhagic cystitis due to carbenicillin disodium developed experienced this related disorder four years later when first exposed to ticarcillin. Neither reduction of the dose nor substitution of one semisynthetic penicillin for another (piperacillin for ticarcillin, ticarcillin for carbenicillin) prevented recurrence of the disorder. The clinical importance of either form of cystitis induced by semisynthetic penicillins is uncertain, as is the risk for progression to interstitial nephritis.

Allergy to semisynthetic penicillins in cystic fibrosis.

Allergic reactions to anti-Pseudomonal penicillin derivatives are an increasing problem in therapy of cystic fibrosis lung disease. We evaluated 15 patients, ages 12 to 37 years, with documented allergic reactions to carbenicillin, ticarcillin, or piperacillin. Intradermal skin test reactions were positive for benzylpenicillin in seven patients, penicilloyl-polylysine in one, and ticarcillin or piperacillin in eight, for a total of 11 of 11 tested. Results of radioallergosorbent testing to penicilloyl conjugates were positive in eight of 14 patients and equivocal in four others. Overall, skin tests or RAST results were positive in 13 of 15 patients. All patients were desensitized with a semisynthetic penicillin by continuous serial intravenous infusion of 10-fold dose increments, beginning with 10(-6) of the therapeutic dose. Desensitization was successful in 25 of 26 instances. After intravenously administered therapy, maintenance of desensitization with dicloxacillin orally was unsuccessful in four of six patients. We conclude that (1) allergy to semisynthetic penicillins in cystic fibrosis usually is IgE mediated; (2) such allergy can be evaluated by skin testing; (3) it can be safely and in most cases successfully treated by intravenous desensitization; and (4) allergic patients should be desensitized on each subsequent admission for intravenously administered therapy.

Comparative efficacy of piperacillin versus carbenicillin for complicated urinary tract infections.

In this controlled, randomized clinical trial we compared piperacillin and carbenicillin in the treatment of complicated urinary tract infections. 24 patients received piperacillin 150 mg/kg/day for 7.2 +/- 2.75 days and 17 patients received carbenicillin 200 mg/kg/day for 7.5 +/- 2.90 days. Patients were evaluated for clinical and bacteriologic responses and tolerance to therapy. Although the clinical cure rate significantly favored carbenicillin treatment (p less than 0.01), the sum of the percentages of cases with clinical cure and clinical improvement were similar between groups: 91.6% for piperacillin and 88.2% for carbenicillin. The bacteriologic cure rates for piperacillin and carbenicillin patients (54.1 and 47.0%, respectively) were not significantly different (p greater than 0.05). The low cure rates in our study were probably the result of uncorrected/uncorrectable genitourinary tract abnormalities. Superinfections developed in 12.5 and 17.6% of piperacillin and carbenicillin patients, respectively, and were due to Klebsiella pneumonia, Proteus mirabilis, Citrobacter diversus, and Pseudomonas aeruginosa. Overall, side effects were mild, reversible, and did not require discontinuation of treatment. However, carbenicillin caused elevations in liver enzymes more frequently than piperacillin (p less than 0.05). Based on our data, we recommend reserving piperacillin monotherapy for patients who are poor candidates for aminoglycosides, or are on severe sodium restriction, and have serious complicated urinary tract infections due to susceptible organisms. We do not recommend piperacillin alone for empiric treatment of complicated urinary tract infections.

Combination of amikacin and carbenicillin with or without cefazolin as empirical treatment of febrile neutropenic patients. The International Antimicrobial Therapy Project Group of the European Organization for Research and Treatment of Cancer.

A total of 841 febrile neutropenic patients from 20 centers were randomized to receive carbenicillin (or ticarcillin) plus amikacin or these antibiotics plus cefazolin to compare outcome and incidence of nephrotoxicity. Infection with Escherichia coli, Klebsiella species, Pseudomonas aeruginosa, or Staphylococcus aureus accounted for most of the microbiologically documented febrile episodes. The response to therapy was similar in the two treatment groups for all infections and for bacteremia. Improvement occurred in 35 (64%) of 55 bacteremic patients treated with two antibiotics and 39 (65%) of 60 treated with three antibiotics. An increase in serum creatinine to 2 mg/dL over baseline occurred in eight (2.1%) of 381 patients in the former and in 50 (2.4%) of 364 patients in the latter group. Thus, the two antibiotic regimens were equal in efficacy and in nephrotoxicity. Although not the primary focus of this study, a significant decrease in incidence of infection, including bacteremias, was found in neutropenic patients treated with any oral intestine decontamination regimen.

Comparative efficacy and tolerance study of azlocillin and carbenicillin in patients with cystic fibrosis: a double blind study.

Azlocillin, a new acylureidopenicillin, has been compared to carbenicillin in a controlled, double-blind study for acute exacerbations of pulmonary infections in 29 patients with cystic fibrosis. Twenty-six patients were valid for final analysis of their therapeutic results; 12 treated with azlocillin (group I) at mean dosage of 252 mg/kg/day for a mean duration of 13.2 days of treatment, and 14 treated with carbenicillin (group II) at mean dosage of 505 mg/kg/day for a median duration of 12.6 days. Except for one patient of group I who had Staphylococcus aureus in sputum culture, the remaining patients all had Pseudomonas aeruginosa of mucoid colonial morphology with or without the same organism of rough variety in their sputum culture. Therapeutic efficacy was evaluated according to our scoring system of ten clinical factors, five radiological and five pulmonary function factors with 5 points each and 100 points total if perfect. The percentage of patients who improved by 20% or greater in clinical scores was found in 91.7% of patients in group I and 64.3% of patients in group II, which was statistically significantly different. The percentage of patients who improved by 20% or greater in total scores was found in 80% of group I and 45.5% of group II patients, which was less significant than the evaluation of clinical scores alone. Azlocillin was well tolerated and safe in the dosage employed. Its optimal dosage for patients with cystic fibrosis should be established.

Piperacillin v Carbenicillin in the therapy for serious infections.

One hundred seven patients were treated with either piperacillin (56) or carbenicillin (51) in an open randomized trial of hospitalized patients with pleuropulmonary (40), urinary tract (26), gynecologic (21), skin and soft-tissue (eight), joint (five), bone (three), and miscellaneous other infections (four). Patients with urinary tract infections were given 150 mg/kg/day of piperacillin sodium or 200 mg/kg/day or carbenicillin sodium in divided doses every six hours intravenously. Patients with other infections were given 250 mg/kg/day of piperacillin sodium and 450 mg/kg/day of carbenicillin sodium; 53/56 (95%) patients treated with piperacillin and 45/51 (88%) patients treated with carbenicillin were cured clinically. In general, the drugs were well tolerated. There were, however, more adverse experiences in the groups taking carbenicillin. Of special interest was the finding of liver function test abnormalities in 17/78 (21%) carbenicillin recipients (evaluative and nonevaluative cases). We concluded that piperacillin was effective and safe. It has potential for use in a great variety of infections.

Preliminary report comparing piperacillin and carbenicillin for complicated urinary tract infections.

Piperacillin is a new semisynthetic penicillin with a broad spectrum of in vitro activity against common gram-negative urinary tract pathogens. We compared the efficacy and safety of piperacillin versus carbenicillin in patients with complicated urinary tract infection. A total of 56 adult patients (mean age 55 years) in stable medical condition with 1 or more structural genitourinary abnormalities entered the study. Of these patients 27 were evaluated for antibiotic efficacy. There were 20 lower tract and 7 upper tract infections, of which 17 were acute and 10 were chronic. Patients were randomized into 2 groups: 17 patients with 18 organisms received single agent treatment with 181 mg. per kg. intravenous piperacillin daily for 6 days and 10 patients with 11 organisms received 270 mg. per kg. intravenous carbenicillin daily for 6 days. Infecting organisms were Escherichia coli 45 per cent, Proteus mirabilis 14 per cent, Klebsiella pneumoniae 14 per cent. Enterobacter species 10 per cent, Pseudomonas aeruginosa 7 per cent and so forth. Antimicrobial susceptibility assessed by measurement of minimal inhibitory concentration and disk diffusion zone size demonstrated superior activity of piperacillin over carbenicillin for most micro-organisms tested. All patients responded clinically. The bacteriologic cure rate was 72 per cent at 5 to 9 days after therapy in both groups. Three patients who received piperacillin had urosepsis and were cured. No resistance emerged during therapy. Superinfections developed in 5 patients on carbenicillin (50 per cent) and in 4 patients on piperacillin (24 per cent), and none was resistant to piperacillin. Superinfections were attributed to catheterization and structural genitourinary abnormalities. The over-all incidence of adverse effects in patients on piperacillin was less than that of those on carbenicillin, 31 and 51 per cent respectively. Side effects in both groups were mild and did not require discontinuation of therapy. There were no significant alterations in fluid and electrolyte balance, or hematologic or renal function.