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[Value of enzymuria during antibacterial therapy].

Enzymuria is a well known parameter of evaluation of drugs nephrotoxicity, particularly of antibiotics. Alanine aminopeptidase (AAP), gamma-glutamyltransferase (GGT) and N-acetyl-bêta-D-glucosaminidase activities were measured in native urine. This study included 19 patients treated by an association of netilmicin-vancomycin. Enzymuria was measured on 24 hours urines at J0 then every two days during treatment. Enzymuria increased 24 or 48 hours after the beginning of the treatment. The Principal Components Analysis (PCA) of the results of enzymuria, seric urea and creatininemia shows the presence of two groups of responses. The first principal component exhibits two populations: the patients with pathological seric urea and pathological seric creatinine and the others. The PCA does not allow this discrimination using only the results of enzymuria; in contrast, with these results, the patients may be classified by the PCA on the basis of treatment duration. The enzymuria allows the clear identification of nephrotoxic drugs but does not allow the prediction of renal injury or of its aggravation.

Acetylglucosaminidase↗

[Dosage adjustment of drugs during continuous hemofiltration. Results and practical consequences of a prospective clinical study].

In 43 ICU patients undergoing continuous volume constant hemofiltration (CVHF), the pharmacokinetics of 12 drugs were investigated to ensure correct dosage adjustments. Under conditions of CVHF, maximum doses were defined for cefotaxime, ceftazidime, digoxin, digitoxin, imipenem, metronidazole++, netilmicin, phenobarbital, phenytoin, theophylline, tobramycin, and vancomycin. For the estimation of sufficient doses without blood level measurements, sieving coefficients (S) were calculated by a new method. In addition, S was integrated as a CVHF-specific factor into a common equation for drug dose adjustment in patients with renal insufficiency. The regression of dosage received from kinetics on blood-level-independent equation adjustment was r = 0.9923. Since the volumes of distribution in ICU patients are variable, it is suggested that further drug monitoring is necessary for toxic drugs.

Adult↗

[Antibiotic prophylaxis in major surgery of the neck and head].

Twenty-two patients undergoing major head and neck surgery were included in a randomized trial to value the efficacy and side effects of parenteral short-term antibiotic prophylaxis of post-operative infections. Two different antibiotic regimens were compared: group A, ceftazidime i.v. (2 g) in three doses (half an hour before surgery, 8 and 16 hours, from the first dose); group B, netilmicin (100 mg) plus clindamycin (600 mg i.v.), following the same chronological schedule. Overall infection rate was 18% (4/22): all post-operative infections occurred in group A patients, including one case of wound infection and 3 mixed infections (wound infection associated with lung infection), with a significant reduction of post-operative infection rate in group B patients (p = 0.045; Fisher's exact test).

Adult↗

Antibacterial activity in vitro of tigemonam, a new oral monobactam.

Using a broth microdilution method, the antibacterial activity of tigemonam, a novel oral monobactam, was evaluated against 217 gram-negative aerobes freshly isolated from clinical specimens. Reference antibiotics were amoxicillin, amoxicillin-sulbactam, cephalexin, cefaclor, norfloxacin, and co-trimoxazole. At a concentration of less than or equal to 8 mg/L, tigemonam inhibited 88% of the members of the Enterobacteriaceae family. Its activity was poor against the nonfermenter pathogens. In comparison with the other drugs, tigemonam generally exhibited superior antibacterial activity (with the exception of norfloxacin, which showed similar potency against the strains tested). Minimum bactericidal concentrations and time-kill determinations indicated that tigemonam showed remarkable bactericidal activity, with a 9% reduction in colony-forming units after 2 h at a dose corresponding to fourfold its minimum inhibitory concentration. When tigemonam was used in combination with netilmicin and amikacin against susceptible representative isolates of Klebsiella pneumoniae, Enterobacter cloacae, Serratia marcescens and Escherichia coli, a synergistic effect was obtained.

Amikacin↗

[Current status of aminoglycoside resistance in hospital Enterobacteriaceae].

We studied the susceptibility of Enterobacteriaceae to four aminoglycosides (gentamicin, tobramycin, netilmicin et amikacin). We determined their phenotypes of resistance by taking into account both the critic concentrations of the CFA (french committee for antibiogram) and the MIC of the main susceptible population of each species. The most frequent phenotypes were GTNt, TNtA and GTNtA. Amikacin resistance including phenotypes were essentially found in Klebsiella and Serratia (35% and 53% of the strains, respectively); with respect to amikacin, the phenotype expression may be insufficient to exceed the sensitive critic concentration of the CFA. Amikacin resistant strains were isolated from chronically infected patients with devices, such as urinary catheters or tracheal cannula. These results suggest a strains or plasmids outbreak.

Amikacin↗

[Post-antibiotic effect of ciprofloxacin alone and in combination on Streptococcus faecalis].

Post-antibiotic effect (PAE) of ciprofloxacin has been studied on 2 strains of S. faecalis in the logarithmic phase after 2 exposure times and at concentrations ranging 0.5-10 times the MIC. At the end of the exposure period the antimicrobial is removed by dilution. Similar PAE is observed for ciprofloxacin and ofloxacin, higher than for pefloxacin. Ciprofloxacin-fosfomycin or ciprofloxacin-vancomycin combinations are indifferent or even antagonistic (vancomycin) in regards to PAE. Ciprofloxacin-penicillin or ciprofloxacin-netilmicin are weakly synergistic.

Ciprofloxacin↗

[Comparative activity of habekacin and 4 other aminoglycosides against gram-negative bacilli. Evolution of resistance].

The activity of 5 aminoglycosides compounds (habekacin, amikacin, gentamicin, netilmicin and tobramycin) was studied by an agar dilution method, against 235 strains of Enterobacteriaceae and 146 other Gram negative bacilli. 79 to 98% of susceptible strains were observed, according to the aminoglycoside compound. Habekacin and amikacin were the most effective, specially against the more frequently resistant bacteria: Enterobacter, Serratia, Hafnia, Acinetobacter, Pseudomonas aeruginosa. In comparison with a previous study, no evolution was observed in the resistance to aminoglycosides.

Acinetobacter↗

In vitro interaction between cefotetan and aminoglycosides on Staphylococcus aureus and coagulase negative staphylococci, both methicillin-susceptible and -resistant.

The authors have evaluated the behavior of the interaction between cefotetan, a new cephalosporin with long acting resistance to the action of beta-lactamases, and gentamicin, amikacin and netilmicin against methicillin-susceptible and -resistant staphylococci. In 65.8% of the cases, drug combinations showed synergic effects. Results were subdivided for susceptibility or resistance to the drugs used in combination. In general, when both drugs were tested against methicillin-susceptible strains the results showed synergism.

Amikacin↗

[Aminoside sensitivity of bacteria isolated in 1984 at the military hospital complex in the Paris region].

The minimal inhibiting concentrations (MIC) of 5 aminosids have been determined by the microdilution method in liquid medium of 4,582 bacterial strains isolated from various pathological samples: 1,039 Staphylococcus, 2,629 Enterobacteria, 759 Pseudomonas and 155 Acinetobacter. The phenotype of resistance has been defined for each strain by listing the antibiotics for which a resistance was observed. The frequencies of the bacterial resistances varied according to the aminosid (gentamicin, sisomicin, tobramycin, netilmicin and amikacin) and to the species studied. For the bacterial species studied, these frequencies of resistance to the aminosid family of antibiotic were weaker in the military hospitals in the district of Paris, than in different civil hospitals where similar studies were conducted.

Acinetobacter↗

[Effect of subinhibitory concentrations of antibiotics on the growth level of bacteria].

The effect of subinhibitory concentrations of 5 antibiotics on the growth rate of 2 bacteria (Staphylococcus aureus and Escherichia coli) has been studied. Chloramphenicol, dibekacin, netilmicin and nalidixic acid have a direct effect on the growth rate. Apparently, aminoglycosides and nalidixic acid have an accompanying effect on the affinity for the energizing substrate. Amoxicillin does not seem to be concerned by this 2 mechanisms. The interest of the estimation of the growth rate by an adaptative algorithm has been pointed out.

Anti-Bacterial Agents↗

Local delivery of antibiotics via an implantable pump in the treatment of osteomyelitis.

Twenty-one patients with osteomyelitis were treated with surgical debridement and local antibiotic therapy. Amikacin (19 patients) or netilmicin (2 patients) was delivered locally via a pump implanted subcutaneously. The outflow catheters were led from the pump subcutaneously to the infected area and placed in the defect created by the surgical debridement. The pump was refilled at intervals, on an outpatient basis. The pump was surgically removed at the conclusion of therapy. Follow-up evaluation was for 12-27 months. The duration of hospitalization was five to 52 days (mean, 23 days). The infusions were sustained for 32-140 days (mean, 63 days). Systemic levels of antibiotics were always below acceptable trough levels. Levels in the wound drainage of the 11 patients who drained after operation were always greater than the upper limit of the assay. Nephrotoxicity and ototoxicity were determined using pre- and posttherapy creatinine clearances and audiograms. Two patients exhibited minimal nephrotoxicity (creatinine clearance of 66 ml/minute and 55 ml/minute; normal, 70 ml/minute). There were no other adverse effects of the antibiotics. Sixteen patients have not drained since removal of the pumps.

Adult↗

[Antibacterial activities of various aminoglycosides against clinically isolated methicillin-resistant Staphylococcus aureus].

Methicillin-resistant Staphylococcus aureus (MRSA) were isolated from samples collected from various patients during 1986, and antibacterial activities of 6 aminoglycosides (AGs) (netilmicin (NTL), gentamicin (GM), sisomicin (SISO), dibekacin (DKB), tobramycin (TOB) and amikacin (AMK] and 4 beta-lactam antibiotics (cefazolin (CEZ), cefmetazole (CMZ), cloxacillin (MCIPC) and methicillin (DMPPC) against these MRSA were evaluated. Among these 6 AGs, NTL was the most potent, and its MIC50 and MIC80 were 1.56 and 3.13 micrograms/ml, respectively. Antibacterial activities of GM, SISO, DKB and TOB were weak, and MIC50's of GM and DKB were both 100 micrograms/ml, while those of SISO and TOB were 50 and greater than 100 micrograms/ml, respectively. Frequency of highly resistant specimens to AMK was rather low and its MIC50 and MIC80 were 12.5 and 25 micrograms/ml, respectively. As for antibacterial activities of the above 4 beta-lactam antibiotics, the MIC50 and MIC80 of CMZ were 6.25 and 12.5 micrograms/ml, respectively, and therefore, its antibacterial activity to MRSA is relatively good. However, MIC50's of CEZ, MCIPC and DMPPC were all greater than 100 micrograms/ml, showing poor antibacterial activities. Recently, MRSA became a problem in various fields of clinical practice, and a number of literatures reporting refractory infections caused by MRSA have been published. Since MRSA is featured as multiply resistant bacteria, it is known that MRSA is resistant to the majority of existing antibiotics (penicillins, cephems, macrolides, AGs, etc.). In 1985, we reported results of our study concerning the antibacterial activities of a number of CEPs and some of AGs against multiply resistant S. aureus including MRSA.(ABSTRACT TRUNCATED AT 250 WORDS)

Amikacin↗

[Comparative study of the in vitro activity of 5 new antibiotics on strains isolated from urinary infections].

In vitro activity of Cefotaxime, Ceftriaxone, Ceftazidime, Piperacillin and Netilmicin against 189 urinary isolates of Enterobacteriaceae, Pseudomonas and Enterococcus has been evaluated. To assess the minimal inhibitory concentrations (MIC), the broth dilution method and the Sensititre system were employed. No considerable differences were found between the two methods. Cefotaxime showed the highest activity against Enterobacteriaceae, the great majority of the isolates being susceptible to 1 microgram/ml or less. Piperacillin showed good activity against Enterococci. Ceftazidime resulted the most active against Pseudomonas.

Cefotaxime↗

Ticarcillin/clavulanic acid (Timentin) compared to metronidazole/netilmicin in preventing postoperative infection after elective colorectal surgery.

A randomized controlled trial was performed to compare the effectiveness of ticarcillin/clavulanic acid to metronidazole/netilmicin in preventing postoperative infections after elective colorectal surgery. Ninety-two patients were randomly allocated to receive three doses of ticarcillin, 3 g, with clavulanic acid, 100 mg every 8 hours, or three doses of metronidazole, 500 mg, and netilmicin, 80 mg intravenously every 8 hours. All patients received a mechanical bowel preparation with 3 L of Go-lytely solution. There were no operative deaths. Eight patients had wound infections--three in the ticarcillin/clavulanic acid group and five in the metronidazole/netilmicin group. One patient in the ticarcillin/clavulanic acid group had an intra-abdominal abscess. There were two anastomotic leaks, one in each group. Ticarcillin/clavulanic acid and metronidazole/netilmicin appear to be equally effective in preventing postoperative infections after elective colorectal surgery.

Adolescent↗

[Possible indications for recently developed antibiotics [author's transl)].

Properties and possible indications of recently developed antibiotics are described. For the treatment of pseudomonas aeruginosa infections of all penicillins azlocillin is the most favourable drug (instead of carbenicillin), for treatment of esch. coli infections it is mezlocillin (instead of ampicillin). Becampicillin and equally amoxycillin are more than ampicillin suitable for oral application (because of almost complete absorption). Cefaclor has a broader spectrum and stronger activity than cefalexin and will replace cefalexin in future. Sisomicin is similar to gentamicin and has no essential advantages. Netilmicin seems to be less oto-and nephrotoxic than gentamicin and may be used with less risk of side-effects in patients with renal insufficiency. Amikacin is reserved for infections by gentamicin-resistant bacteria.

Amikacin↗

Comparative auditory toxicity of aminoglycoside antibiotics in leukopenic patients.

The incidence of auditory toxicity resulting from therapy with ticarcillin (T) (12 g/sq m/day) in combination with gentamicin (G) (200 mg/sq m/day), amikacin (A) (600 mg/dq m/day), or netilmicin (N) (280 mg/sq m/day) was compared. Before administration of these antibiotic combinations to febrile, granulocytopenic patients, baseline audiograms were determined by a pharmacist using a portable audiometer. The before-therapy audiograms for 32 patients receiving T and G, 29 receiving T and A, and 29 receiving T and N were compared with the audiograms after the completion of therapy. The mean length of therapy was seven days. Two patients (6.2%) receiving T and G, one (3.4%) receiving T and N, and one (3.4%) receiving T and A developed auditory toxicity with bilateral decreases of at least 20 decibels at one or more frequencies. The incidence of auditory toxicity secondary to aminoglycoside exposure was low, and the relative auditory toxicity among the three aminoglycosides appeared to be similar.

Agranulocytosis↗

Combination effect of cefmenoxime with four aminoglycosides on Enterobacteriaceae susceptible and moderately susceptible to this new cephalosporin.

The inhibitory combination effect of cefmenoxime with gentamicin, tobramycin, netilmicin and amikacin against 148 Enterobacteriaceae was compared using the checkerboard agar dilution technique. On average 41% of cefmenoxime-moderately susceptible (MIC between 2 and 32 micrograms/ml) or cefmenoxime-resistant (MIC greater than 32 micrograms/ml) strains were inhibited by synergistic, and 23,5% by partial synergistic cefmenoxime-aminoglycosides combinations. Against cefmenoxime-susceptible strains, these rates of synergy or partial synergy were twofold lower, but only one isolate was not susceptible to these combinations. The amikacin-cefmenoxime interaction was the most performant.

Amikacin↗

[Plaster of Paris pellets containing antibiotics in the treatment of bone infection. New combinations of plaster with antibiotics].

The author has tested the action of antibiotic-loaded plaster of Paris loaded pellets in 15 patients with success in 13. Previous studies using plaster of Paris for filling bone defects are noted, plaster being well tolerated and absorbable. Gentamycin, Fucidin and Cefazolin were tested first. In a second series, Netilmicin, Amikacin, Rifamycin and Rifampicin were also used. The preparation of the pellets is fully described. In most instances they can be sterilized by gamma rays except for Fucidin and Cefazolin. Several hundred pellets can be used simultaneously. A study of the elimination of antibiotic in the urine was made. It was concluded that the concentrations obtained by this method in the tissues were highly satisfactory.

Amikacin↗