Glyphosate poisoning - a case report.

Glyphosate is the most commonly used broad-spectrum, non-selective herbicide in the world. The toxicity is supposed to be due to uncoupling of oxidative phosphorylation and the surfactant polyoxyethylene amine (POEA)- mediated cardiotoxicity. Clinical features of this herbicide poisoning are varied, ranging from asymptomatic to even death. There is no antidote and aggressive supportive therapy is the mainstay of treatment for glyphosate poisoning. We present a 69-year-old female patient with suicidal consumption of around 500 ml of Glycel®. Initially, gastric lavage was done and intravenous fluids were given. Within two hours of presentation, the patient developed respiratory distress needing intubation, hypotension needing vasopressor support, and severe lactic acidosis. She also developed acute respiratory distress syndrome, hypokalemia, hypernatremia, and aspiration pneumonia. Our patient was critically ill with multiple poor prognostic factors, but with timely aggressive supportive management, the patient gradually recovered.

Water state effect on drug release from an antibiotic loaded polyurethane matrix containing albumin nanoparticles.

Water mobility plays a crucial role in determining transport properties of small molecules in polymer matrices. In particular, in drug delivery systems, water state affects the pharmacokinetics, especially drug absorption, diffusion and release. In the present study, the state of water in an antibiotic-loaded composite consisting of albumin nanoparticles (BSA(np)) dispersed into a carboxylated polyurethane (PEUA) has been investigated and compared with that of the single drug-loaded components. The antibiotic cefamandole nafate was used as a model drug. DSC analysis, used to evaluate the freezing and non-freezing water fractions in the hydrated samples, showed that in BSA(np) water can adsorb both in the inter-particles regions and inside the particles. With increasing of total adsorbed water amount, the contribution of the freezing water fraction was higher than the non-freezing one. As for PEUA, the majority of water molecules absorbed is in a mobile freezing state (about 60% of the W(tot)). As for the PEUA/BSA(np) composite, the higher polyurethane phase segregation induced by the nanoparticles as well as the higher non-freezing water fraction significantly enhanced drug uptake with respect to PEUA. Moreover, the greater non-freezing water fraction allowed the drug to penetrate within BSA nanoparticles and to give rise then to a controlled drug release. Indeed, the diffusion barrier exerted by nanoparticles and the matrix prolonged the antimicrobial activity from 4 to 9 days. Finally, the higher polyurethane phase segregation also improved composite mechanical properties, as evidenced in stress-strain experiments and dynamic mechanical analysis.

Antibiotic delivery polyurethanes containing albumin and polyallylamine nanoparticles.

Nano-structured polymers delivering an antibiotic for the prevention of medical device-related infections were developed. Systems consisted of bovine serum albumin or polyallylamine nanoparticles alone or entrapped in a polyurethane and then loaded with cefamandole nafate, chosen as a drug model. Results showed that nanoparticles alone were able to adsorb high antibiotic amounts due to their high surface/volume ratio. However, they released cefamandole in an uncontrolled fashion, leading to a rapid loss of antibacterial activity. Improvements in the release control were obtained when CEF loaded and non-loaded nanoparticles were entrapped in a carboxylated polyurethane. For these systems the drug delivery was at least of 50% with respect to nanoparticles alone with a prolonged antimicrobial activity up to 9 days.

Should we change antibiotic prophylaxis for lung surgery? Postoperative pneumonia is the critical issue.

BACKGROUND: The recommended antibiotic prophylaxis by second-generation cephalosporins reduces the incidence of wound infection and empyema, but its effectiveness on postoperative pneumonias (POPs) after major lung resection lacks demonstration. We investigated risk factors and characteristics of POPs occurring when antibiotic prophylaxis by second-generation cephalosporin or an alternative prophylaxis targeting organisms responsible for bronchial colonization was used. METHODS: An 18-month prospective study on all patients undergoing lung resections for noninfectious disease was performed. Prophylaxis by cefamandole (3 g/24 h, over 48 hours) was used during the first 6 months, whereas amoxicillin-clavulanate (6 g/24 h, over 24 hours) was used during the subsequent 12 months. Intraoperative bronchial aspirates were systematically cultured. Patients with suspicion of pneumonia underwent bronchoscopic sampling for culture. RESULTS: Included were 168 patients in the first period and 277 patients in the second period. The incidence of POP decreased by 45% during the second period (P = 0.0027). A significant reduction in antibiotic therapy requirement for postoperative infections (P = 0.0044) was also observed. Thirty-day mortality decreased from 6.5% to 2.9% (P = 0.06). Multivariate analysis showed that type of resection, intraoperative colonization, chronic obstructive pulmonary disease, gender, body mass index, and type of prophylaxis were independent risk factors of POP. A case control-study that matched patients of the two periods according to these risk factors (except for antibiotic prophylaxis) confirmed that the incidence of POP was lowered during the second period. CONCLUSIONS: Targeted antibiotic prophylaxis may decrease the rate of POPs after lung resection and improve outcome.

[Regional lymphotropic antibiotic therapy as a part of comprehensive treatment of children with purulent-inflammatory diseases of maxillofacial region].

126 children (aged 3-14 years) with severe purulent-inflammatory maxillofacial lesions underwent complex treatment: lymhotropic method of antibiotic (cefamabol) therapy was used in 64 of them. Clinical, microbiological and pharmacokinetic investigations have shown the method of lymphotropic regional antibiotic therapy to be effective and feasible to treat purulent-inflammatory maxillofacial lesions in children.

IgA pemphigus--occurrence of anti-desmocollin 1 and anti-desmoglein 1 antibody reactivity in an individual patient.

BACKGROUND: IgA pemphigus is a rare pustular autoimmune disease with exclusive IgA anti-keratinocyte cell surface antibody reactivity. Two subtypes have been discerned: in the subcorneal pustular dermatosis type, desmocollin 1 has been identified as a targeted autoantigen, while in few cases of the intraepidermal neutrophilic type, IgA anti-desmoglein 1 or IgA anti-desmoglein 3 reactivity has been demonstrated. PATIENTS AND METHODS: A 48-year-old white male presented with generalized large confluent pustules. Skin pathology was assessed by histology and direct immunofluorescence analysis. IgG/IgA autoantibodies against desmoglein 1/3 and desmocollin 1 were measured by ELISA and indirect immunofluorescence using desmocollin 1 cDNA-transfected COS7 cells, respectively. RESULTS: Histopathology revealed subcorneal pustules and direct immunofluorescence microscopy exclusively showed in vivo bound IgA with an intercellular pattern in the epidermis. Desmocollin 1 was identified as a target of IgA autoantibodies by indirect immunofluorescence microscopy utilizing desmocollin 1 cDNA-transfected COS7 cells. In addition, IgA anti-desmoglein 1 reactivity was demonstrated by ELISA. Neither IgA anti-desmoglein 3 nor IgG anti-desmoglein 1/3 autoantibodies were present. CONCLUSIONS: Both desmocollin 1 and desmoglein 1 were autoantigens in this patient with IgA pemphigus and a distinct clinical presentation. To our knowledge, this is the first IgA pemphigus case with dual autoantibody reactivity.

Clinical pharmacokinetics of cefamandole and ceftazidime administered by continuous intravenous infusion.

In view of the results of animal studies as well as theoretical considerations, continuous administration of beta-lactam antibiotics should be superior to intermittent administration because of the close relationship between efficacy and the duration of time in which the concentration of unbound antibiotics in plasma remains above the MIC. The aim of the present study was to establish the pharmacokinetic parameters of cefamandole and ceftazidime for patients receiving these cephalosporins by continuous infusion. The interindividual differences in the concentrations in plasma at the steady state were mainly attributable to variations in renal function, as estimated by the rate of creatinine clearance. Using these results, we derived formulas for both cephalosporins that can be used to determine on an individual basis the total daily dose needed to obtain a therapeutic concentration in plasma. These formulas were tested with a group of subsequent patients and proved to be practical and fairly reliable. For some patients, a correction for a possible underestimation of the renal clearance at presentation might be required.

New polymer-antibiotic systems to inhibit bacterial biofilm formation: a suitable approach to prevent central venous catheter-associated infections.

Intravascular catheters are widely employed in medical practice. However, complications such as local or systemic infections are frequently related to their use. The significant increase in this type of nosocomial infection has prompted the search for new strategies to prevent them. This paper reports on an experimental model to prevent catheter-related infections based on the adsorption of a beta-lactam antibiotic (cefamandole nafate) on functionalized urethane polymers. The polyurethanes synthesized were used to coat a commercial central venous catheter. The influence of functional groups on the polymer-antibiotic interaction was analyzed and the kinetics of the antibiotic release from the catheters was dynamically studied. We were able to realize a polymer-antibiotic system able to inhibit bacterial growth up to 7 days. These promising results have encouraged us to extend this experimental model to other polymer-antibiotic systems in order to identify those allowing bacterial growth inhibition for longer times.

[Coagulation abnormalities after total hip prosthesis (THP), a rare cause: antibiotic prophylaxis]. / Anomalies de la coagulation après prothèse totale de hanche (PTH), une cause rare: l'antibioprophylaxie.

A 87-year-old patient developed coagulation abnormality following hip surgery related to the prophylactic use of cefamandole. Cefamandole as others cephalosporins with a methyl-tetrazol-thiol lateral chain interferes with the vitamin K regeneration cycle as do oral anticoagulants. Therefore, the use of others antibiotics or systematic vitamin K1 supplementation or single dose of cefamandole is recommended for patients with renal failure or with malnutrition. Vitamin K1 supplementation is a simple method resulting in complete resolution of the coagulation disorder.

[Alpha-1-antitrypsin in early infections after hip prosthesis surgery]. / L'alpha-1-antitrypsine dans les infections précoces après prothèse de hanche.

PURPOSE OF THE STUDY: The aim of this work was to determine whether erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and alpha-1-antitrypsin (A1AT) levels are correlated significantly with early postoperative infectious complications after hip prosthetic surgery. MATERIALS AND METHODS: This prospective study was conducted on 100 total hip replacements performed between 1994 and 1995. ESR, CRP and A1AT were obtained before surgery then at 1, 2 and 6 weeks after surgery. RESULTS: Seven bacteriologically proven cases of infection were reported. Infection was considered to be superficial if it did not extend deeper than the muscles fascia. There was a strong statistical correlation between A1AT level and infection for all postoperative times (p<0.0001). A1AT was highly sensitive (87.5 p. 100) and specific (85.8 p. 100) for infection compared with ESR (sensibility 70 p. 100 and specificity 65.9 p. 100) and CRP (sensitivity 63.6 p. 100 and specificity 80.1 p. 100). DISCUSSION AND CONCLUSION: In our hands, A1AT can be a most useful diagnostic tool for infection after prosthesis hip surgery. Although not totally specific, it is highly sensitive for infection compared with other tools such as ESR and CRP more frequently used. These findings suggest an avenue of research on the role of A1AT in infectious complications after prosthetic joint surgery.

The impact of penicillinase on cefamandole treatment and prophylaxis of experimental endocarditis due to methicillin-resistant Staphylococcus aureus.

Beta-lactams active against methicillin-resistant Staphylococcus aureus (MRSA) must resist penicillinase hydrolysis and bind penicillin-binding protein 2A (PBP 2A). Cefamandole might share these properties. When tested against 2 isogenic pairs of MRSA that produced or did not produce penicillinase, MICs of cefamandole (8-32 mg/L) were not affected by penicillinase, and cefamandole had a > or =40 times greater PBP 2A affinity than did methicillin. In rats, constant serum levels of 100 mg/L cefamandole successfully treated experimental endocarditis due to penicillinase-negative isolates but failed against penicillinase-producing organisms. This suggested that penicillinase produced in infected vegetations might hydrolyze the drug. Indeed, cefamandole was slowly degraded by penicillinase in vitro. Moreover, its efficacy was restored by combination with sulbactam in vivo. Cefamandole also uniformly prevented MRSA endocarditis in prophylaxis experiments, a setting in which bacteria were not yet clustered in the vegetations. Thus, while cefamandole treatment was limited by penicillinase, the drug was still successful for prophylaxis of experimental MRSA endocarditis.

Early transition to oral antibiotic therapy for community-acquired pneumonia: duration of therapy, clinical outcomes, and cost analysis.

Our objective was to compare therapeutic outcome and analyse cost-benefit of a 'conventional' (7-day course of i.v. antibiotic therapy) vs. an abbreviated (2-day i.v. antibiotic course followed by 'switch' to oral antibiotics) therapy for in-patients with community-acquired pneumonia (CAP). We used a multicenter prospective, randomized, parallel group with a 28 day follow-up, at the University-based teaching hospitals: The Medical Center of Louisiana in New Orleans, LA and hospitals listed in the acknowledgement. Ninety-five patients were randomized to receive either a 'conventional' course of intravenous antibiotic therapy with cefamandole 1 g i.v. every 6 h for 7 days (n = 37), or an abbreviated course of intravenous therapy with cefamandole (1 g i.v. every 6 h for 2 days) followed by oral therapy with cefaclor (500 mg every 8 h for 5 days). No difference was found in the clinical courses, cure rates, survival or the resolution of the chest radiograph abnormalities among the two groups. The mean duration of therapy (6.88 days for the conventional group compared to 7-30 days for the early oral therapy group) and the frequencies of overall symptomatic improvement (97% vs. 95%, respectively) were similar in both groups. Patients who received early oral therapy had shorter hospital stays (7.3 vs. 9.71 days, P = 0.01), and a lower total cost of care ($2953 vs. $5002, P < 0.05). It was concluded that early transition to an oral antibiotic after an abbreviated course of intravenous therapy in CAP is substantially less expensive and has comparable efficacy to conventional intravenous therapy. Altering physicians' customary management of hospitalized patients with CAP can reduce costs with no appreciable additional risk of adverse patient outcome.

Concentration of cefamandole in plasma and tissues of patients undergoing cardiac surgery: the influence of different cefamandole dosage.

OBJECTIVE: To develop an improved regimen of antibiotic prophylaxis in cardiac surgery, three antibiotic prophylactic regimens for patients scheduled to have elective cardiothoracic surgery involving a median sternotomy were evaluated. DESIGN: A prospective, randomized, unblinded study. SETTING: A university teaching hospital. PARTICIPANTS: Sixty-nine men scheduled for elective coronary artery bypass grafting (CABG) with extracorporeal circulation (ECC) were included in the study. INTERVENTIONS: The patients were selected at random to receive 2 g of cefamandole (CM) at induction of anesthesia (group 1, n = 24), or 2 g of CM at the beginning of anesthesia followed by an additional dose (2 g) immediately after onset of cardiopulmonary bypass (CPB) (group 2, n = 22), or 4 g of CM just at the initiation of anesthesia (group 3, n = 23). Samples from the mammary artery, sternum, and plasma were obtained at various intervals after injection of the antibiotic (10 minutes intravenously) to compare antibiotic levels, assayed for CM concentrations, with high-pressure liquid chromatography (HPLC) and plasma bactericidal activity as well as infectious complications in these sites as a function of time for the three groups. MEASUREMENTS AND MAIN RESULTS: There were no significant differences in biometric data, duration of hospitalization, or management of cardiopulmonary bypass, including urinary tract drainage and infusion volume. The mean plasma t1/2 (distributive or alpha-phase) before bypass was 51.7 +/- 16.7 minutes for group 1 and 2 patients and 54.9 +/- 15.9 minutes for group 3 patients. CM plasma values were significantly higher in group 2 (170.3 +/- 105.8 micrograms/mL) than in groups 1 and 3 (111.8 +/- 42.2 micrograms/mL, 101.2 +/- 57.2 micrograms/mL) at the end of bypass periods (p < 0.05). The antibiotic contents of mammary artery and sternum samples of group 2 (15.6 +/- 4.7 micrograms/mL, 9.5 +/- 4.7 micrograms/mL) were significantly higher after completion of CPB compared with group 1 (5.7 +/- 1.9 micrograms/mL, 3.8 +/- 2.9 micrograms/mL) and group 3 (6.3 +/- 3.5 micrograms/mL, 3.6 +/- 1.8 micrograms/mL) (p < 0.05). There were no significant differences in distribution of micro-organisms among the three groups, but two patients of groups 1 and 3 with plasma and tissue CM levels below minimal inhibitor concentration (MIC90) for Hemophilus influencea, E coli, Proteus ssp and Klebsiella ssp after completion of CPB, respectively, developed a pneumonia postoperatively caused by Hemophilus influencea (1), E coli (1) and Klebsiella ssp (2) (p < 0.05). CONCLUSIONS: It would be preferable to infuse the antibiotic shortly before the operative procedure. However, to keep tissue and plasma CM values more than MIC90 for common pathogens during the time period studied, a second infusion of 2 g of CM administered after onset of CPB suggests better protection against the risk of microbial infections. Therefore, the findings might be important for the choice of antibiotic prophylaxis, particularly for high-risk patients.

[Cost increase due to incorrect antibiotic prophylaxis in visceral, thoracic and vascular surgery]. / Mehrkosten infolge inkorrekter Antibiotikaprophylaxe in der Viszeral-, Thorax- und Gefässchirurgie.

We analysed retrospectively 460 patients treated between March 1991 and February 1992, in respect to a correct perioperative antibiotic prophylaxis. In our opinion a correct prophylaxis is a single-shot application, with a second dose given only during long operations (over 3 hours) or when blood loss is great. 240 of the 460 patients analysed (52.2%) were given antibiotics prophylactically. In 76.6% of the cases (n = 184) the prophylaxis was performed correctly. In 23.4% (n = 56) antibiotic application was extended indiscriminately into the post-operative phase. This calculated to costs three times higher than those actually necessary, causing us to spend 22,000-Swiss francs unnecessarily, one twelfth of the total cost of antibiotic treatment in our hospital each year. For economic reasons as well as to keep growth of resistant strains in check, an antibiotic prophylaxis should be restricted to the perioperative period in most cases as a single shot only.

Effect of time interval on tissue concentrations of cephalosporins after tourniquet inflation. Highest levels achieved by administration 20 minutes before inflation.

We studied the effect of different time intervals between antibiotic administration and tourniquet inflation in 62 patients undergoing reconstructive surgery in the lower extremities. The in vivo concentrations in soft tissue and bone of 3 cephalosporins (ceftazidime, ceftriaxone and ceforanide) were determined. Our findings suggest that the highest tissue concentrations were achieved by administration 20 min before tourniquet inflation.

Synergistic enhancement of in vitro antimicrobial activity of cefmetazole and cefotiam, cefamandole or cefoperazone in combination against methicillin-sensitive and -resistant Staphylococcus aureus. II. Effect of inoculum size.

The inoculum effect was studied on the activity of cefmetazole and cefotiam, cefamandole or cefoperazone alone and in combination against 9 strains of methicillin-sensitive Staphylococcus aureus (MSSA) and 20 strains of methicillin-resistant Staphylococcus aureus (MRSA) by means of the checkerboard titration method with Mueller-Hinton agar plate using 10(6) and 10(8) CFU/ml. The antimicrobial activity against MSSA and MRSA was potentiated synergistically in combination of cefmetazole and these cephalosporins either with inoculum size 10(6) or 10(8) CFU/ml. At a concentration of cephalosporins < or = 6.25 micrograms/ml, the combination effect of cefmetazole and cefotiam or cefamandole against MRSA was more potent than that of cefmetazole and cefoperazone. With a higher inoculum size the effect was reduced. Under these conditions with a low dose level of drugs, the enhancement of the activity of cefmetazole by cefotiam was least influenced by inoculum size among cephalosporins studied.

Synergistic enhancement of in vitro antimicrobial activity of cefmetazole and cefazolin, cefotiam, cefamandole or cefoperazone in combination against methicillin-sensitive and -resistant Staphylococcus aureus. I. Effect of NaCl.

The in vitro antimicrobial activity of cephamycin, e.g. cefmetazole and cephalosporin, such as cefazolin, cefotiam, cefamandole and cefoperazone, alone and in combination, was studied employing 9 strains of methicillin-sensitive Staphylococcus aureus (MSSA) and 30 strains of methicillin-resistant Staphylococcus aureus (MRSA). Using the checkerboard agar dilution method, strong synergism was demonstrable in a majority of MSSA and MRSA strains for cefmetazole combined with these cephalosporins, with the minimum fractional inhibitory concentration index < or = 0.5. In the presence of a concentration < or = 6.25 micrograms/ml of these cephalosporins in Mueller-Hinton agar medium, the activity of cefmetazole against MRSA was most prominently potentiated by cefotiam, followed by cefamandole, cefazolin and cefoperazone. At a concentration of 12.5 micrograms/ml, cefotiam and cefamandole showed a similar effect in potentiation of cefmetazole activity. In hypertonic agar medium containing 4% NaCl, these synergistic combination effects were reduced. However, the activity of cefmetazole and cefamandole in combination under these conditions was influenced to a lesser extent and more potent than that of other combinations.

[Voluminous inguinal hernias can also be treated under local anesthesia]. / Les volumineuses hernies inguinales peuvent aussi être traitées sous anesthésie locale.

In patients with a large inguinal hernia, surgeons are usually reluctant to use a local anesthesia as described in the Shouldice technique. The purpose of this study was to appreciate the efficiency of such a technique. Routine local anesthesia used 200 cc of 0.5% lidocaine injected subcutaneously in the groin area and more deeply, near the anterior superior iliac spine in order to achieve a nerve block of the genital branches of the ilioinguinal and genitofemoral nerves. If necessary, the peritoneal sac is injected with lidocaine: it is usually not opened, just pushed back into the abdomen. At the end of the procedure, the estimated size of the peritoneal sac, the presence of pain, the necessity of converting the local anesthetic technique into an other procedure and the use of a prosthesis were recorded in the patient's charts. From January 1986 to December 1992, all patients with an inguinal hernia more than 6 cm in diameter, were included in the study. 111 consecutive patients were defined as having a large hernia and were operated by one of the authors. 3 patients were excluded, following general anesthesia as the first approach, males leaving 108 cases. The mean age was 59.8 years (range: 21 to 92). There were 103 males and 5 females, 60 right hernias, 37 left and 11 bilateral of which 4 were bilateral and large, giving a total of 112 large hernias. The mean diameter of the sac was 8.6 cm (range: 6 to 30). 7 patients were operated for recurrent large hernia. During the procedure, 9 patients reported pain which necessitated repeated injections of local anesthetic. The local procedure never had to be converted into general anesthesia. All patients had a Shouldice repair and none required the use of a prosthesis. Patients were reviewed after a mean of 36 months of postoperative course (from 5 to 79 months). No hernia recurrence was observed, five patients had "residual" pain.

Teicoplanin versus cefamandole in the prevention of infection in total hip replacement.

In a prospective, controlled, single-blind study the efficacy of teicoplanin versus cefamandole in preventing infections in total hip replacement was investigated in 496 consecutive patients. A single intravenous dose of teicoplanin (400 mg) was as effective as two intravenous doses of cefamandole (2 g before and 1 g after surgery). No major complications were observed in either group. Infective wound complications were observed only in the cefamandole group. These infections, although not dangerous for the patients, required supplementary antibiotic treatment in all cases. Teicoplanin is a reasonable choice as a prophylactic agent in orthopaedic surgery when a high risk of infection due to staphylococci is present.