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PubMed1984

Influence of subinhibitory concentrations of antibiotics on opsonization and phagocytosis of Pseudomonas aeruginosa by human polymorphonuclear leukocytes.

To determine whether pretreating Pseudomonas aeruginosa with antibiotics had an effect on phagocytosis, a serum-resistant clinical isolate was incubated with one-third of the minimum inhibitory concentrations of azlocillin, carbenicillin, cefoperazone, fosfomycin, netilmicin and piperacillin respectively prior to exposure to human polymorphonuclear leukocytes. The phagocytic process was measured by assaying radiolabeled bacteria. The uptake rates of untreated and antibiotic treated bacteria did not differ when normal human serum was used for opsonization. However, when the serum was heated to inactivate the complement system, its opsonic activity for untreated as well as for fosfomycin and netilmicin treated pseudomonas was removed and phagocytosis did not take place. In contrast, bacteria pretreated with the betalactam antibiotics still underwent phagocytosis, as also confirmed by electron microscopy. Even in the presence of rabbit immune serum untreated bacteria still required the participation of the complement system for optimal opsonization, whereas bacteria treated with beta-lactam antibiotics did not.

Anti-Bacterial Agents↗

PubMedDate not supplied

Endocarditis due to Aerococcus urinae: diagnostic tests, fatty acid composition and killing kinetics.

Two cases of Aerococcus urinae endocarditis are reported. The organism is not included in any database of commercial identification systems at this time. Formation of tetrades and positive reactions for leucine arylamidase and beta-glucuronidase pointed strongly to A. urinae. The cellular fatty acid pattern was similar to that of Aerococcus viridans, with predominantly C16:0, C18:1 omega 9c and C18:0; the presence of C18:1 omega 7t differentiated our isolates from A. viridans and can support the diagnosis of A. urinae. Furthermore, susceptibility to penicillin but resistance to cotrimoxazole represents a pattern opposite to that of A. viridans. Minimal inhibition concentrations of gentamicin and netilmicin were < or = 64 mg/l but those of tobramycin were > or = 256 mg/l. Penicillin combined with either gentamicin or netilmicin showed distinct synergy in killing kinetics. These combinations seem to be the appropriate regimen to treat A. urinae endocarditis.

Aged↗

PubMed2004

Antibiotic resistance of urinary tract pathogens and rationale for empirical intravenous therapy.

Empirical antibiotic treatment in urinary tract infection (UTI) in children must rely on surveillance data on the epidemiology and resistance patterns of common uropathogens. A retrospective analysis of bacteria isolated from children with UTI irrespective of underlying disease or pre-treatment was performed at the University Hospital of Freiburg, Germany, in 1997, and from 1999 to 2001. In the first study period, 261 positive urine samples and in the second period 684 positive samples were analyzed. Escherichia coli (57.2%) was the leading uropathogen followed by Enterococcus spp. (13.7%), Pseudomonas aeruginosa (7.0%), Proteus spp. (5.9%), Klebsiella spp. (4.7%), and Enterobacter/Citrobacter spp. (4.3%). Almost 50% of the E. coli isolates were resistant to ampicillin, but effectively no resistance against cephalosporins, aminogylcosides, ciprofloxacin, nitrofurantoin, and imipenem was observed. In Enterococcus spp. the resistance to ampicillin was about 15% and 40% to netilmicin, while none of the latter showed high-level aminoglycoside resistance. In P. aeruginosa, there was no resistance to aminoglycosides. No difference in resistance patterns between the two study periods was observed. We conclude that an empirical combination treatment of ampicillin and gentamicin, netilmicin, or tobramycin is appropriate in children with UTI independent of pre-treatment or underlying disease. This therapy should be clinically efficacious, well tolerated, and cost effective, and should prevent unnecessary development of antimicrobial resistance.

Bacteria↗

PubMed1989

Selective membrane toxicity of aminoglycoside antibiotics in membrane vesicles isolated from proximal renal tubules of the rat.

A considerable body of evidence suggests that the nephrotoxic potential of aminoglycoside antibiotics may be associated with the degree of membrane binding and subsequent membrane damage in the renal tubules. In this study, we isolated functional basolateral and luminal membrane vesicles from rat renal cortex, incubated each membrane type in the presence of 1 mM concentrations of either neomycin, netilmicin, gentamicin, hydroxygentamicin, or amikacin, and monitored the activities of the marker enzymes alkaline phosphatase (ALP) and lambda-glutamyltransferase (GGT) (luminal) or ouabain-sensitive Na+,K+-ATPase (basolateral) to determine if there were any selective drug-related alterations of enzyme activities. While none of the five aminoglycosides had any substantive effect upon enzyme activities of luminal vesicles, all five drugs inhibited the basolateral marker enzyme. Neomycin produced the greatest inhibition, hydroxygentamicin and amikacin the least, and gentamicin and netilmicin were intermediate in the inhibition of the enzyme. These results are in accordance with the known relative nephrotoxicity of these same drugs and indicate the usefulness of isolated renal membrane vesicles for in vitro toxicological studies of novel aminoglycosides.

Alkaline Phosphatase↗

PubMed1992

Human pancreatic tissue concentration of bactericidal antibiotics.

Pancreatic infection represents the most important cause of fatal outcome in human acute pancreatitis. In a comparative analysis, human pancreatic tissue concentrations of 10 different bactericidal antibiotics were determined in 89 patients undergoing pancreatic surgery. Concentrations of the antibiotics were determined in the blood and pancreatic tissue using high-pressure liquid chromatography. Pancreatic tissue concentrations 120 minutes after intravenous administration were as follows: mezlocillin, 19.0 mg/kg; piperacillin, 20.3 mg/kg; cefotaxime, 9.1 mg/kg; ceftizoxime, 7.9 mg/kg; netilmicin, 0.4 mg/kg; tobramycin, 0.4 mg/kg; ofloxacin, 1.7 mg/kg; ciprofloxacin, 0.9 mg/kg; imipenem, 6.0 mg/kg; metronidazole, 3.5 mg/kg. Three groups of antibiotics were established: group A, substances with low tissue concentrations (netilmicin, tobramycin), which were below the minimal inhibitory concentrations of most bacteria found in pancreatic infection; group B, antibiotics with pancreatic tissue concentrations which were sufficient to inhibit some but not all bacteria in pancreatic infection (mezlocillin, piperacillin, ceftizoxime, cefotaxime); group C, substances with high pancreatic tissue levels as well as high bactericidal activity against most of the germs present in pancreatic infection (ciprofloxacin, ofloxacin, imipenem). These data could serve as the basis for adequate antibiotic prophylaxis or treatment of pancreatic infection.

Adult↗

PubMed1988

Observations on multiple drug resistance in coagulase-negative staphylococci isolated in hospitals from 1975 to 1985.

Drug resistance in coagulase-negative staphylococci (CNS) isolated in hospitals since 1975 was analysed using routine laboratory data registered on a microcomputer. Resistance increased substantially in CNS during the years, especially in Staphylococcus epidermidis isolates, of which more than 50% were multiply drug resistant by 1985. Among the methicillin-resistant CNS strains, resistance to gentamicin rose from 0% in 1975 to 76% in 1985. Co-resistance to kanamycin, gentamicin, and in some cases netilmicin seemed to replace co-resistance to kanamycin and streptomycin in S. epidermidis. Gentamicin and netilmicin usage in hospital increased tenfold from 1976 to 1985.

Aminoglycosides↗

PubMedDate not supplied

Evaluation of in vitro antimicrobial activity of lomefloxacin against staphylococci, enterococci, Enterobacteriaceae, and Pseudomonas aeruginosa.

In vitro antimicrobial activity of lomefloxacin and other antibiotics (norfloxacin, beta-lactams, cotrimoxazole, netilmicin, and miokamycin) was evaluated against 317 clinical isolates including Staphylococcus aureus, enterococci, Enterobacteriaceae, and Pseudomonas aeruginosa. Lomefloxacin showed a high in vitro activity against a wide variety of bacterial species. Against Enterobacteriaceae, lomefloxacin displayed the highest activity (MIC90S, less than or equal to 1 microgram/ml), and it was usually more active than ampicillin and netilmicin, and often more active than cotrimoxazole. Lomefloxacin showed a good antimicrobial activity also against both methicillin-susceptible and methicillin-resistant S. aureus, as it was able to inhibit 90% of staphylococcal strains at a concentration less than or equal to 2 micrograms/ml. Against enterococci and P. aeruginosa, lomefloxacin was usually less active (MIC90S, 8 micrograms/ml). As compared to norfloxacin, lomefloxacin displayed an overall similar activity against staphylococci and enterococci, but appeared less active against Gram-negative bacteria. Bactericidal activity of lomefloxacin against E. coli, when assayed by a novel method, proved to be high, and results indicate that an oral dose of 200 mg of lomefloxacin should exert a very high bactericidal activity against E. coli in urinary tract infections, even in those sustained by large bacterial populations.

4-Quinolones↗

PubMed2005

Hospital-based intensive monitoring of antibiotic-induced adverse events in a university hospital.

Hospital-based monitoring is one of the methods used to collect data about drug prescriptions and adverse events. The aim of this 20-day observational prospective study was to evaluate the frequency and type of adverse reaction to antibiotics, and predisposing risk factors in inpatients in six departments of a university hospital (ophthalmology, paediatrics, internal medicine, general surgery, infectious diseases, anaesthesiology and intensive care). The data on all inpatients undergoing antibiotic treatment were collected by physicians trained by our team and validated by an expert panel. Data were recorded on pre-formatted confidential cards (MIO-card). In the 171 inpatients evaluated (125 adults: 39.5% male, mean age 61.6 years, range 21-93; and 46 children: 50% male; mean age 4.75 years, range 3 months-12 years), cefazolin (19.9%), chloramphenicol (18.6%), ceftriaxone (15.4%) and netilmicin (12.9%) were the most frequently used antibiotics. Adverse events occurred in four adults and three children: one had leucopenia (trimethoprim/sulfamethoxazole), one nephrotoxicity (netilmicin+teicoplanin) and one nephrotoxicity (cefotaxime), one diarrhoea (ceftriaxone), one neurotoxicity (isoniazid), one angioneurotic oedema (piperacillin) and one skin rashes (ceftriaxone). A number of strategies (educative and persuasive, facilitative and restrictive) have been proposed to improve antibiotic use. Our study suggests that hospital-based monitoring is a good method with which to detect links between drug exposure and adverse drug reactions in children and adults.

Adult↗

PubMed1978

Gas-liquid chromatographic method for the assay of aminoglycoside antibiotics in serum.

A gas-liquid chromatographic (GLC) method is presented for the rapid analysis of gentamicin, tobramycin, netilmicin, and amikacin from human serum. This procedure may have application to all aminoglycoside drugs. The three isomers of gentamicin are resolved as two bands, while tobramycin, netilmicin, and amikacin appear in this system as single bands. Normal serum constituents do not interfere with chromatograms. Thus far, no assay interference has been found in cases where other drugs and antibiotics were administered concurrently with aminoglycoside therapy. Dose-response data demonstrating linear recovery are included for all four aminoglycosides as well as a comparison of the GLC method with the microbiological method for the assay of gentamicin and amikacin. Quantitation is based upon the relative response of the antibiotics to a fixed amount of the internal standards, either kanamycin A or paromomycin B. These standards are clearly resolved as symmetrical peaks from the antibiotics of assay interest. Isothermal chromatographic analysis time is less than 8 min, while total assay time per single serum specimen is approximately 50 min. Preparation of serum includes: precipitation, evaporative drying of the supernatant, a two-stage derivatization (N-trimethylsilylimidazole, N-heptafluorobutyrylimidazole), and a single hexane extraction with a water wash. The methodology described may be applied to the analysis of other compounds (e.g., saccharides, amino-saccharides, amino acids, etc.) which do not rapidly partition into an organic phase.

Amikacin↗

PubMed2002

Effects on antibiotic resistance of Staphylococcus epidermidis following adhesion to polymethylmethacrylate and to silicone surfaces.

A number of studies appears to give emphasis to the role of prosthetic materials in determining microbial adherence and resistance to host defence and drug therapy. Aim of this study was to explore whether the direct contact with biomaterial substrata of different chemical nature could influence bacterial behaviour, determining possible changes in the bacteria population as far as antibiotic resistance is concerned. To this end, susceptibility to penicillin, erythromycin, clindamycin, cefamandole, imipenem, vancomycin, ciprofloxacin. ampicillin, cefazolin, trimethoprim-sulfamethoxazole, chloramphenicol, amikacin and netilmicin was evaluated in a methicillin-, gentamicin- and tobramycin-resistant Staphylococcus epidermidis strain, after in vitro adhesion to polymethylmethacrylate (PM MA) and to silicone elastomer. The susceptibility to antibiotics of both adherent bacteria and bacteria which, although exposed to the materials, had not undergone adhesion was measured as bacterial growth inhibition area onto a plate antibiogram. according to Kirby-Bauer and using an image analyser system. The results obtained suggest that the two test materials considered in this study were capable to condition bacterial behaviour. In particular. the adhesion onto PMMA surfaces induced a marked and significant decrease in susceptibility to the following beta-lactam antibiotics: cefamandole (32%), cefazolin (23%), imipenem (27%), ampicillin (31%). Moreover, PMMA caused a lower but significant reduction in resistance to vancomycin (15%), chloramphenicol (16%), amikacin (13%). netilmicin (13%), erythromycin (11%) trimethoprim-sulfamethoxazole (13%). In contrast, the adhesion onto silicone elastomer appeared to influence bacterial changes to a lesser extent and elicited a significant decrease in susceptibility only to cefazolin (10%) and amikacin (11). Further studies are required to thoroughly investigate the mechanisms of these variations, even though, also according to other authors, one of the best conceivable conclusions is that some material substrata can lead to selection of variant adhesive bacteria with increased antibiotic resistance.

Biocompatible Materials↗

PubMed1984

An automated high-performance liquid chromatographic method for the determination of aminoglycosides in serum using pre-column sample clean-up and derivatization.

An automated high-performance liquid chromatographic method for the determination of the aminoglycosides amikacin, dibekacin, gentamicin, netilmicin, sisomicin and tobramycin is described. The procedure involves sample clean-up by adsorption of the aminoglycosides on a pre-column, subsequent derivatization with o-phthalaldehyde and on-line separation of derivatives by column switching. A short cation-exchange column serving concurrently as a guard column in combination with a reversed-phase column was used for separation. Except for the determination of netilmicin an internal standard consisting of an aminoglycoside was used in each assay. The signals of the aminoglycosides determined were linear within the range of 1-16 mg/l serum. The inter-assay imprecision (n = 10) calculated as coefficient of variation was less than 6%. The results were obtained within 20 min after injection of the serum sample. Easy performance and flexibility make the procedure feasible for therapeutic drug monitoring.

Aminoglycosides↗

PubMed2002

Determination of gentamicin in urine samples after inhalation by reversed-phase high-performance liquid chromatography using pre-column derivatisation with o-phthalaldehyde.

Gentamicin and netilmicin (internal standard) were extracted from urine using C18 solid-phase extraction cartridges (94.3% recovery) and then derivatised with o-phthalaldehyde and 3-mercaptopropionic acid. The derivative was stable for >6 h. The mobile phase methanol-glacial acetic acid-water (800:20:180, v/v), contained 0.02 M sodium heptanesulfonic acid, pH 3.4, and was passed at 1.0 ml min(-1) through a C18 column with fluorescence detection (excitation 340 nm, emission 418 nm). The four main components of gentamicin (C1, C1a, C2, C2a) and netilmicin, the internal standard, were separated. Using the C1a gentamicin peak, linearity was demonstrated from 0.5 to 10 microg ml(-1) and the limit of detection was 75 microg l(-1). Following 80-mg oral, 40-mg intravenous and 80-mg nebulised administration, the mean (SD) gentamicin urinary excretion was zero, 38.27 (0.96) and 1.93 (0.28) mg, respectively. Despite the relatively low lung deposition following inhalation of gentamicin the assay developed can be used to quantify the low urinary concentrations. Using this assay it should be possible to carry out urinary pharmacokinetic studies to identify the relative lung deposition of gentamicin following different methods of inhalation.

Adult↗

PubMed1988

Determination of the rate-limiting segment of aminoglycoside nucleotidyltransferase 2''-I by pH and viscosity-dependent kinetics.

Aminoglycoside nucleotidyltransferase 2''-I follows a Theorell-Chance kinetic mechanism in which turnover is controlled by the rate-limiting release of the final product (Q), a nucleotidylated aminoglycoside [Gates, C. A., & Northrop, D. B. (1988) Biochemistry (second of three papers in this issue)]. The effects of viscosity on the kinetic constants of netilmicin, gentamicin C1, and sisomicin aminoglycoside substrates are as follows: no change in the substrate inhibition constants of all three antibiotics, a small but significant and highly unusual increase in Vmax/Km for netilmicin but large, normal decreases for gentamicin C1 and sisomicin, and marked decreases in the maximal velocities for all three. The lack of effect on substrate inhibition provides essential control experiments, signifying that glycerol does not interfere with binding of aminoglycosides to EQ and that the steady-state distribution of EQ does not increase as the release of Q is slowed by a viscosogen. The decrease in the Vmax/Km of better substrates indicates dominance by a diffusion-controlled component in the catalytic segment, attributed to the release of pyrophosphate. The presence of an increase in the Vmax/Km of the poor substrate, however, is inexplicable in terms of either single or multiple diffusion-controlled steps. Instead, it is here attributed to an equilibrium between conformers of the enzyme-nucleotide complex in which glycerol favors the conformation necessary for binding of aminoglycosides. The decrease in Vmax is consistent with the diffusion-controlled release of the final product determining enzymatic turnover.(ABSTRACT TRUNCATED AT 250 WORDS)

Escherichia coli↗

PubMed1985

Effect of aminoglycosides on the disposition of thyroid hormones and thyroglobulin.

Our study was designed to confirm the potential effects of three aminoglycosides on the disposition of thyroid hormones. Twenty-seven patients diagnosed with either cellulitis (n = 19), chronic osteitis (n = 4), or an abscess (n = 4) were selected. Thirteen patients received tobramycin, 60 to 100 mg iv q. 8 h., plus cloxacillin, 1 gm iv q. 4 h.; seven patients received netilmicin, 40 to 120 mg iv q. 8 h., plus cloxacillin, 1 gm iv q. 4 h.; and seven patients received either cloxacillin, 1.5 gm iv q. 4 h., or cefoperazone, 2 to 4 gm iv q. 12 h. for at least 7 days. Another group of six normal subjects received neomycin, 0.5 gm po q. 6 h. for 7 days. All these subjects had normal thyroid function before antibiotic dosing and none had thyroid function abnormalities. Tobramycin and cloxacillin/cefoperazone did not influence thyroid function. Netilmicin decreased the total serum concentrations of triiodothyronine (T3) from 114 +/- 9 to 75 +/- 7 ng/dl (P less than 0.01), probably because of increased clearance, as the T3 free fraction increased from 0.43% +/- 0.02% to 0.49% +/- 0.02% (P less than 0.05). Thyroxine (T4) and reverse T3 (rT3) levels were not affected. Neomycin decreased T3 levels from 104 +/- 8 to 92 +/- 7 ng/dl (P less than 0.05) and the serum concentrations of thyroglobulin from 17.3 +/- 2.0 to 11.7 +/- 2.0 ng/ml (P less than 0.001). Because T4 and rT3 levels did not change, our results suggest that neomycin may have directly affected the gland. We conclude that some aminoglycosides can alter the disposition of thyroid hormones.

Adult↗

PubMed2001

The changing nature of aminoglycoside resistance mechanisms and prevalence of newly recognized resistance mechanisms in Turkey.

OBJECTIVE: To determine the most frequently occurring individual and combined resistance mechanisms in Gram-negative bacteria resistant to any of the clinically available aminoglycosides in Turkey, and to compare these mechanisms with those found in smaller, earlier studies. METHODS: Aminoglycoside resistance mechanisms in Gram-negative isolates resistant to either gentamicin, tobramycin, netilmicin or amikacin collected in different regions of Turkey were evaluated both phenotypically and genotypically using 12 aminoglycosides and up to 22 aminoglycoside resistance gene probes. RESULTS: Among 696 aminoglycoside-resistant Gram-negative bacteria, resistance rates were very high for gentamicin (94.5%), tobramycin (82.4%), netilmicin (53.6%), and amikacin (49.7%). Although isepamicin was the most active aminoglycoside against Gram-negative bacteria, increased resistance (29.7%) was found and resistance rates were higher than those in most of the other countries surveyed in earlier studies. The most common aminoglycoside resistance mechanisms (AAC(3)-II (GTN), AAC(6')-I (TNA), and ANT(2")-I (GT)) in the earlier studies were also found in the present isolates of Klebsiella spp., Enterobacter spp. and Escherichia coli, with increased complexity. In addition to these old mechanisms, two new aminoglycoside resistance mechanisms, namely AAC(6')-III (TNAI) and AAC(6')-IV (GTNA), were also found at significant frequencies (11.9% and 26.9%, respectively) in these isolates of Enterobacteriaceae (n = 435). Among the isolates of Pseudomonas spp. (n = 150), in addition to the increased complexity of enzymatic resistance mechanisms (AAC(3)-I (16.6%), AAC(6')-II (29.3%), AAC(6')-III (19.3%), ANT(2")-I (40%)), permeability resistance seemed to be responsible for the high rates of resistance to aminoglycosides. CONCLUSION: The results of this study indicated increased resistance to clinically available aminoglycosides, including isepamicin, even though it was the most active, as a result of both the presence of new aminoglycoside resistance mechanisms and the increased complexity of all mechanisms, including permeability resistance, particularly in Pseudomonas in Turkey.

Aminoglycosides↗

PubMed1990

Epidemiology of antibiotic resistance in human isolates of Enterobacteriaceae in Sicily.

The authors have studied the antimicrobial susceptibility of 1073 clinical isolates of various genera of Enterobacteriaceae (collected during the period July-December 1988) to ampicillin, piperacillin, cefotaxime, ceftazidime, ceftriaxone, aztreonam, imipenem, gentamicin, amikacin, netilmicin, norfloxacin, and ciprofloxacin. Antimicrobial susceptibility was determined by Bauer-Kirby disk diffusion method. Of 1073 tested bacteria, 704 (65.6%) produced beta-lactamase detectable by nitrocefin test. The highest percentage of resistant strains occurred with ampicillin (70%) followed by piperacillin (24%) and cefotaxime (19%). Lower percentages of resistant strains were found for gentamicin (10%), aztreonam (8%), netilmicin (7%), norfloxacin (5%) and amikacin (4%). Two percent of the strains were resistant to ciprofloxacin and 0.5% to imipenem. The incidence of resistance in Klebsiella sp., Enterobacter sp., E. coli and Proteus sp. was compared to that found among 872 strains isolated during July-Dec. 1984. In all the Enterobacteriaceae, mainly Enterobacter sp., the increase in the resistance was high for ampicillin, piperacillin and cefotaxime and lower for gentamicin.

Drug Resistance, Microbial↗

PubMed1991

In-vitro activity of ciprofloxacin and other beta-lactam antibiotics against gentamicin- and carbenicillin-resistant isolates of Pseudomonas aeruginosa.

The susceptibilities of gentamicin- and carbenicillin-resistant clinical isolates of Pseudomonas aeruginosa to newer beta-lactams, netilmicin and ciprofloxacin were studied by a broth microdilution technique. Imipenem, aztreonam and ceftazidime were active against most of the P. aeruginosa strains with minimum inhibitory concentration (MIC) for 90% of the isolates at clinically achievable levels. Piperacillin, azlocillin, cefotaxime, ceftriaxone, cefsulodin, cefoperazone and netilmicin showed poor activity against these organisms, ciprofloxacin exhibited poor activity, inhibiting only 30% of these strains.

Anti-Bacterial Agents↗

PubMed1979

Species-specific resistance to antimocrobial synergism in Streptococcus faecium and Streptococcus faecalis.

Combinations of penicillin with various aminoglycosidic aminocyclitols were tested against a collection of clinical isolates of Streptococcus faecium in vitro and were used to treat endocarditis caused by S. faecium in the rabbit model. S. faecium proved more resistant to penicillin than Streptococcus faecalis. Even more striking, however, was the resistance to in vitro synergism by combinations of penicillin and various aminoglycosides. At clinically achievable concentrations, penicillin-gentamicin was the only combination that was synergistic against all strains that were tested. Combinations of penicillin and streptomycin and penicillin and amikacin were synergistic only against those strains that were not highly resistant to streptomycin and kanamycin, respectively. Combinations of penicillin with kanamycin, tobramycin, sisomicin, or netilmicin failed to produce synergism against any of these strains. The possible clinical significance of these findings was verified by use of the rabbit model of endocarditis. Combinations of penicillin with gentamicin or streptomycin were synergistic in the therapy of endocarditis that was produced by a strain of S. faecium that did not have a high level of resistance to aminoglycosides. However, the combination of penicillin and netilmicin was no more effective than penicillin alone.

Aminoglycosides↗