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PubMed1985

[Effect of BRL 25000 (clavulanic acid-amoxicillin) on bacterial flora in human feces].

BRL 25000 (187.5 and 375 mg tablets), a formulation of CVA-K and AMPC in the ratio of 1:2, and AMPC (as control drug) were administered to healthy volunteers, aged 20 approximately 28 years and weighing 60 approximately 85 kg (68.8 kg, on average). Each drug was administered 3 times a day (after meals) for 5 days and the volunteers were separated into 3 groups of 4 subjects each. The effect on the fecal flora was studied before dosage, during administration (day 3 and 5) and day 3 and 5 after the administration course was completed. Studies were undertaken to isolate C. difficile on the last day of administration and 3 and 5 days after administration had ceased. Fecal concentrations and the susceptibility of the isolates to AMPC, CVA-K and BRL 25000 were measured. Side effects and laboratory findings were studied. The results obtained were as follows: 1. In BRL 25000 (187.5 mg X 3/day) group, the population of E. coli was on average, 1 X 10(6) approximately 9 X 10(6) cells/g feces before initiation of administration and it increased by 2 logarithms 3 and 5 days after initiation of administration. By 3 and 5 days after end of administration, the E. coli population was similar to the initial population. The population of Klebsiella sp. was 1 X 10(6) approximately 9 X 10(6) cells/g feces on average before commencement of dosage and it increased by 2 logarithms 3 days after initiation of administration but there was no consistent change in the Klebsiella sp. population thereafter. The Enterobacter sp., population was not consistent neither was the population of other Enterobacteriaceae. In total, the mean Enterobacteriaceae population was 1 X 10(7) approximately 9 X 10(7) cells/g feces before initiation of administration and increased by 2 logarithms 3 days after initiation of administration, and then returned to the initial level 5 days after end of administration. No consistent changes in population were noted for the other Gram-negative bacilli. The Staphylococcus sp. population was 1 X 10(6) approximately 9 X 10(6) cells/g feces on average before initiation of administration. This organism was detected in only 1 case 3 days after initiation of administration and in another 5 days after initiation of administration, thereafter, the population was similar to the initial population.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗
PubMed1985

[Experimental and clinical trials of BRL 25000 (clavulanic acid-amoxicillin) granules in the field of pediatrics].

MICs of BRL 25000, a combination of a newly developed beta-lactamase inhibitor CVA and AMPC in the ratio of 1 to 2, were determined against a number of bacterial strains and compared with those of AMPC, CVA, CEX and CCL. The 98 bacterial strains tested included 2-S. aureus, 23-H. influenzae, 25-E. coli, 22-K. pneumoniae and 26-P. mirabilis. In pharmacokinetic studies, BRL 25000 medium granules were administered to groups of 3 male subjects, aged between 7 years 8 months and 9 years 5 months, at doses of 10, 15 and 20 mg/kg, 2 hours after a meal. The resultant serum and urine concentrations and drug recoveries were measured. Furthermore, BRL 25000 was administered to a total 43 patients (2-pharyngitis, 8-tonsillitis, 3-bronchitis, 2-pneumonia and 28-urinary tract infection) whom clinically evaluable. An average daily dosage of 45.3 mg/kg was given, in 3 or 4 divided doses, for a period of 8 days on average. Clinical and bacteriological effects as well as side effects were studied. In the microbiological studies on 98 clinical strains, including beta-lactamase negative bacteria, BRL 25000 showed MICs against the Gram-positive cocci (2-S. aureus) superior to the other 4 drugs at inoculum sizes of 10(8) and 10(6) cells/ml. For the Gram-negative bacilli, against H. influenzae at inoculum sizes of 10(8) and 10(6) cells/ml, BRL 25000 was inferior in the small MIC range but superior in the large MIC range to AMPC, and was superior to the other 3 drugs. Against E. coli at an inoculum of 10(8) cells/ml, BRL 25000 showed antibacterial activity next to AMPC and CCL whilst at an inoculum of 10(6) cells/ml, it was inferior in the small MIC range but superior in the large MIC range to AMPC and CEX and was inferior to CCL but superior to CVA. Against K. pneumoniae at an inoculum of 10(8) cells/ml, BRL 25000 was equal to AMPC, CVA and CEX but inferior to CCL, whilst at an inoculum of 10(6) cells/ml, it was inferior to CCL but superior to the other 3 drugs. Against P. mirabilis at inoculum sizes of 10(8) and 10(6) cells/ml, BRL 25000 was inferior in the small MIC range but equal or superior in the large MIC range to AMPC, and was superior to CVA and CEX.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗
PubMed1998

Rational prescribing of extended-spectrum penicillin beta-lactamase inhibitor combinations: focus on ticarcillin/clavulanic acid.

OBJECTIVE: To provide an overview of the clinical pharmacokinetics and pharmacodynamics of ticarcillin/clavulanic acid and to reassess traditional dosage recommendations based on contemporary pharmacokinetic and pharmacodynamic principles. DATA SOURCES: Published ticarcillin and clavulanic acid pharmacokinetic data derived from infants and children combined with data obtained from a rigorous, dose-escalation study performed in 12 healthy adults. Pharmacodynamic correlates were derived from published in vitro susceptibility data for the combination drug ticarcillin/clavulanic acid. DATA SYNTHESIS: Limited differences were observed in the pharmacokinetic disposition profiles between ticarcillin and clavulanic acid and relative to subject age. Integration of these data with defined pathogen minimum inhibitory concentrations underscores the appropriateness of an extended dosing interval (e.g., q8h to q12h) for many infections and demonstrates the probable therapeutic interchangeability of the following three intravenous dosing regimens: 3.1 g every 6 hours, 75 mg/kg every 8 hours, and 100 mg/kg every 12 hours of a 30:1 ticarcillin/clavulanic acid combination. CONCLUSIONS: Integration of pharmacokinetic and pharmacodynamic data is an appropriate means to assess/reassess dosing recommendations for antimicrobial agents. Initial ticarcillin/clavulanic acid dose recommendations did not account for known dynamic interactions for this combination antibiotic. Pharmacokinetic data in infants, children, and adults support a less frequent dosing interval (q8h to q12h) for the treatment of infections arising outside the central nervous system.

Age Factors↗
PubMed2004

Antimicrobial susceptibility of Enterococcus faecalis isolated from canals of root filled teeth with periapical lesions.

AIM: To test, in vitro, the susceptibility to different antibiotics of Enterococcus faecalis isolates from canals of root filled teeth with periapical lesions. METHODOLOGY: Twenty-one E. faecalis isolates, from canals of root filled teeth with persisting periapical lesions, were tested for their antibiotic susceptibilities. The following antibiotics were used: benzylpenicillin, amoxicillin, amoxicillin-clavulanic acid, erythromycin, azithromycin, vancomycin, chloramphenicol, tetracycline, doxycycline, ciprofloxacin and moxifloxacin. Minimal inhibitory concentrations (MICs) for the antimicrobial agents were determined using the E-test System (AB BIODISK, Solna, Sweden), and the E. faecalis strains classified as susceptible or resistant according to the guidelines of National Committee for Clinical Laboratory Standards (NCCLS). The strains were also tested for beta-lactamase production with nitrocefin (Oxoid, Basingstoke, UK). RESULTS: All strains were susceptible to penicillins in vitro, however, the MICs of amoxicillin and amoxicillin-clavulanic acid (MIC(90) = 0.75 microg mL(-1)) were lower than for benzylpenicillin (MIC(90) = 3.0 microg mL(-1)). All strains studied were also susceptible to vancomycin and moxifloxacin, whilst 95.2% were susceptible to chloramphenicol. Amongst the isolates, 85.7% were susceptible to tetracycline and doxycycline and 80.9% to ciprofloxacin. The MIC of erythromycin ranged from 0.38 to >256 microg mL(-1); only 28.5% of the strains were susceptible (MIC < or = 0.5 microg mL(-1)). Limited susceptibility was also observed with azithromycin which was active against only 14.2% of isolates. No strains produced beta-lactamase. CONCLUSION: Enterococcus faecalis isolates were completely susceptible, in vitro, to amoxicillin, amoxicillin-clavulanic acid, vancomycin and moxifloxacin. Most isolates were susceptible to chloramphenicol, tetracycline, doxycycline or ciprofloxacin. Erythromycin and azithromycin were least effective.

Anti-Bacterial Agents↗
PubMed1996

Effect of amplification or targeted disruption of the beta-lactamase gene of Nocardia lactamdurans on cephamycin biosynthesis.

The bla gene of the cephamycin cluster of Nocardia lactamdurans has been subeloned in the shuttle plasmids pULVK2 and pULVK2A and amplified in N. lactamdurans LC411. The transformants showed two- to threefold higher beta-lactamase activity. Formation of beta-lactamase preceded the onset of cephamycin biosynthesis. The beta-lactamase of N. lactamdurans inactivated penicillins and, to a lesser extent, cephalosporin C but did not hydrolyse cephamycin C. This beta-lactamase was highly sensitive to clavulanic acid (50% inhibition was observed at 0.48 microgram/ml clavulanic acid). The N. lactamdurans bla gene was disrupted in vivo by inertion of the kanamycin-resistance gene. Three bla-disrupted mutants, BD4, BD8 and BD12, were selected that lacked beta-lactamase activity. Overexpresion of the bla gene resulted in N. lactamdurans transformants that were resistant to penicillin whereas mutants in which the bla gene was disrupted were super-sensitive to this antibiotic. The three N. lactamdurans mutants with the bla gene disrupted showed a significant increase of cephamycin biosynthesis in solid medium, whereas transformants with the amplified bla gene produced reduced levels of cephamycin. The cephamycin-overproducing Merck strain N. lactamdurans MA4213 showed no detectable levels of beta-lactamase activity. The beta-lactamase plays a negative role in cephamycin biosynthesis in solid medium, but not in liquid medium.

Anti-Bacterial Agents↗
PubMed1991

Novel transferable extended-spectrum beta-lactamase (SHV-6) from Klebsiella pneumoniae conferring selective resistance to ceftazidime.

A clinical isolate of Klebsiella pneumoniae sensu lato isolated from throat and a blood culture taken from a neutropenic patient treated for 2 weeks with ceftazidime and vancomycin was resistant to ceftazidime (MIC: 32 micrograms/ml) and moderately susceptible to aztreonam (MIC: 4 micrograms/ml). The isolate contained a plasmid of 180 kb which, when transferred to Escherichia coli by conjugation, conferred resistance to ceftazidime and tetracycline. The transconjugant had decreased susceptibility to ceftazidime (128-fold) and aztreonam (8-fold). Clavulanic acid and sulbactam each inhibited the resistance and clavulanic acid showed a synergistic effect when associated with ceftazidime and aztreonam. An extended-spectrum beta-lactamase with an isoelectric point of 7.6 was detected in the clinical isolates from blood and its transconjugant. This beta-lactamase showed similar substrate and inhibition profiles to SHV-1. In particular it did not hydrolyse ceftazidime. Hybridization with an intragenic probe for SHV-3 indicates that this beta-lactamase is an SHV-type enzyme. We propose that this novel CAZ-type extended-spectrum beta-lactamase be named SHV-6.

Ceftazidime↗
PubMed2002

Resistance to beta-lactam antibiotics: structure and mechanism based design of beta-lactamase inhibitors.

Resistance to antibiotics is currently a major health concern in treating infectious diseases. The most common mechanism of resistance to beta-lactam antibiotics is the production of beta-lactamases, which destroy beta-lactam antibiotics before they reach the bacterial target. Combination therapy, which involves treatment with a beta-lactam antibiotic and a beta-lactamase inhibitor, has been successfully used to control resistance during last two decades. Due to the lack of effectiveness of the currently available beta-lactamase inhibitors against class C enzymes and new variants of beta-lactamases, there is a need to develop an inhibitor with broad-spectrum activity. Since the discovery of clavulanic acid, there has been an enormous research effort in this area to identify better antibiotic/inhibitor combinations and to understand the molecular bases for interactions between beta-lactam antibiotics, beta-lactamases, and beta-lactamase inhibitors. This review describes some of the structure- and mechanism-based approaches to design of new beta-lactamase inhibitors and the study of probable mechanisms of inhibition using X-ray, electrospray ionization mass spectrometry, and molecular modeling techniques.

Anti-Bacterial Agents↗
PubMed1993

Efficacy and tolerability of brodimoprim in pharyngotonsillitis in children.

160 children with an average age of 9 years (range 6-15) affected by acute bacterial tonsillitis, were selected and assigned, following an open, parallel group design to: a) brodimoprim at the dose of 10 mg/kg on the first day, in single administration, and of 5 mg/kg on the following days; b) cotrimoxazole suspension, at the dosage of 6 mg of trimethoprim/kg/day, in two daily administrations; c) amoxicillin with clavulanic acid suspension (amoxi-clavulanate) 50 mg/kg every 12 hours. Quantity of pharynx and tonsillar exudate, pharynx pain, dysphonia and dysphagia were checked at the basal time, 3rd, 7th and at the last day of therapy. These symptoms were evaluated using a four-step rating scale. The evolution of body temperature was measured at two different times (1 and 5 o'clock p.m.), until the end of treatment, foreseen five days after disappearance of fever. Microbiological evaluation through a pharynx swab was performed at the beginning and at the end of therapy. Side-effects were registered during all the observation period. Lab-tests were carried out at the enrollment and at the end of treatment. The frequency and intensity of symptoms decreased significantly in all treatment groups. In comparison with amoxi-clavulanate, the brodimoprim group showed an earlier improvement (3rd day) of the clinical situation and a significantly better regression of pharynx exudate (p < 0.01), pharynx pain (p < 0.05) and dysphonia (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1999

Escherichia coli ATCC 35218 as a quality control isolate for susceptibility testing of Haemophilus influenzae with haemophilus test medium.

Current National Committee for Clinical Laboratory Standards (NCCLS) susceptibility guidelines for quality control testing with Haemophilus influenzae do not include a beta-lactamase-producing strain that could detect the deterioration of the beta-lactamase inhibitor components of amoxicillin-clavulanic acid, ampicillin-sulbactam, and piperacillin-tazobactam. The objective of the study was to determine if comparable quality control results for Escherichia coli ATCC 35218, a beta-lactamase-producing strain, would be produced for the three beta-lactam-beta-lactamase inhibitor agents with Haemophilus test medium and Mueller-Hinton medium. The criteria used in this study to determine if Haemophilus test medium was acceptable for quality control testing of E. coli ATCC 35218 was that 100% of the results obtained with an antimicrobial agent-methodology combination needed to be within the acceptable NCCLS ranges established with Mueller-Hinton medium. The MIC testing results obtained by the broth microdilution and E-test methods with amoxicillin-clavulanic acid and piperacillin-tazobactam were all within the NCCLS ranges; however, the results obtained with ampicillin-sulbactam by both methods were not within the NCCLS ranges. Acceptable results were obtained by the disk diffusion methodology with ampicillin-sulbactam and piperacillin-tazobactam but not with amoxicillin-clavulanic acid. When performing susceptibility testing with H. influenzae with the beta-lactam-beta-lactamase inhibitors, in addition to quality control testing with H. influenzae ATCC 49247, testing of E. coli ATCC 35218 on Haemophilus test medium is an effective way to monitor the beta-lactamase inhibitors in some antimicrobial agent-methodology combinations.

Culture Media↗
PubMed1993

Interactions between active-site-serine beta-lactamases and mechanism-based inactivators: a kinetic study and an overview.

The interactions between three class A beta-lactamases and three beta-lactamase inactivators (clavulanic acid, sulbactam and olivanic acid MM13902) were studied. Interestingly, the interaction between the Streptomyces cacaoi beta-lactamase and clavulanate indicated little irreversible inactivation. With sulbactam, irreversible inactivation was found to occur with the three studied enzymes, but no evidence for transiently inactivated adducts was found. Irreversible inactivation of the S. albus G and S. cacaoi enzymes was particularly slow. With olivanate, irreversible inactivation was also observed with the three enzymes, but with the S. cacaoi enzyme, no hydrolysis could be detected. A tentative summary of the results found in the literature is also presented (including 6 beta-halogenopenicillanates), and the general conclusions underline the diversity of the mechanisms and the wide variations of the rate constants observed when class A beta-lactamases interact with beta-lactamase inactivators, in agreement with the behaviours of the same enzymes towards their good and poor substrates.

Actinomycetales↗
PubMed2003

In vitro activities of novel oxapenems, alone and in combination with ceftazidime, against gram-positive and gram-negative organisms.

Four novel oxapenem compounds (i.e., AM-112, AM-113, AM-114, and AM-115) were investigated for their beta-lactamase inhibitory activity against a panel of isolated class A, C, and D enzymes, which included expanded-spectrum beta-lactamase enzymes (ESBLs). The oxapenems were potent beta-lactamase inhibitors. Activity varied within the group, with AM-113 and AM-114 proving to be the most active compounds. The 50% inhibitory concentrations for these agents were up to 100,000-fold lower than that of clavulanic acid against class C and D enzymes. As a group, the oxapenems were more potent than clavulanic acid against enzymes from all classes. The ability of these compounds to protect ceftazidime from hydrolysis by beta-lactamase-producing strains was evaluated by MIC tests that combined ceftazidime and each oxapenem in a 1:1 or 2:1 ratio. The oxapenems markedly reduced the MICs for ceftazidime against class C hyperproducing strains and strains producing TEM- and SHV-derived ESBLs. There was little difference between the activity of 1:1 and 2:1 combinations of ceftazidime and oxapenem. The oxapenems failed to enhance the activity of ceftazidime against derepressed AmpC-producing Pseudomonas aeruginosa strains.

Anti-Bacterial Agents↗
PubMedDate not supplied

Piperacillin tazobactam compared with co-amoxiclav, ampicillin plus sulbactam and timentin against beta-lactamase-producing clinical isolates of Escherichia coli, Klebsiella pneumoniae and Klebsiella oxytoca.

A total of 266 enterobacterial isolates (Escherichia coli = 190, Klebsiella pneumoniae = 49, K. oxytoca = 27) were tested for susceptibility (Bauer-Kirby agar disk diffusion test and agar dilution procedure) to ampicillin, ampicillin in 10 micrograms/ml of sulbactam, amoxicillin in 4 micrograms/ml of clavulanic acid, piperacillin, piperacillin plus tazobactam (8:1 ratio), ticarcillin and timentin (ticarcillin in 4 micrograms/ml of clavulanic acid). Discrepant results between the two methods of susceptibility testing were categorized as follows: category I = very major [minimal inhibitory concentration (MIC) = resistant, disk diffusion = susceptible] category II = major (MIC = susceptible, disk diffusion = resistant), category III = minor (MIC = intermediate susceptibility, disk diffusion = susceptible), category IV = slight (MIC = resistant, disk diffusion = intermediate), category V = minimal (MIC = susceptible, disk diffusion = intermediate) and category VI = negligible (MIC = intermediate, disk diffusion = resistant). The antibiotics, or combinations with beta-lactamase inhibitors, yielded the following discrepant results: ampicillin (II = 2, V = 1 and VI = 3), co-amoxiclav (I = 5, III = 25, IV = 1 and V = 3), ampicillin plus sulbactam (I = 5, II = 3, III = 1, V = 19 and VI = 1), piperacillin (II = 15, III = 1, V = 15 and VI = 85), piperacillin plus tazobactam (III = 16, IV = 2, V = 1 and VI = 5) and timentin (I = 2, III = 48 and IV = 1).(ABSTRACT TRUNCATED AT 250 WORDS)

Amoxicillin↗
PubMed1983

Amoxycillin/clavulanic acid: the effect of probenecid.

The effect of probenecid on the combination of amoxycillin/clavulanic acid has been compared with the effect on amoxycillin alone and it has been shown that probenecid, whilst producing its expected effect on amoxycillin, did not affect the clavulanic acid concentration of the combination. A possible minor role for tubular secretion of clavulanic acid is discussed.

Adult↗
PubMed1989

[Susceptibility of clinically-isolated problem pathogenic bacteria to broad spectrum antibiotics].

The action of broad-spectrum antibiotics investigated by disc diffusion method on 636 problem bacteria such as S. aureus, Enterobacter, Klebsiella, Pseudomonas, E. coli, Proteus that isolated from various clinical specimens. The highest and lowest ratio of susceptibility were as follows: S. aureus were found sensitive 90% to Netilmicin, 27% to Piperacillin, Enterobacter species 78% to Netilmicin, 25% to Piperacillin, Klebsiella 69% to Amikacin, 20% to Piperacillin, Pseudomonas 66% to Amikacin, 5% to Amoxicillin-Clavulanic acid, E.coli 68% to Netilmicin and Ceftriaxone, 32% to Piperacillin, Proteus 70% to Netilmicin, 43% to Piperacillin, S.epidermidis 90% to Amoxicillin-Clavulanic acid, 60% to Piperacillin.

Amikacin↗
PubMed2005

Nosocomial spread of multi-resistant Klebsiella pneumoniae containing a plasmid encoding multiple beta-lactamases.

Six Klebsiella pneumoniae isolates that exhibited resistance to a wide spectrum of antibiotics were recovered from the intensive care units in the First Affiliated Hospital, Zhejiang University, Hangzhou, China. All isolates contained two plasmids of approximately 95 kb and 200 kb. The 95 kb plasmid was shown to be transferable by conjugation experiments. Isoelectric focusing patterns of the beta-lactamases extracted from the six transconjugants were identical, displaying five pI bands: 5.4, 7.75, 8.0, 8.2 and 8.4. The band corresponding to a pI of 7.75 could be inhibited by cloxacillin but not clavulanic acid, while the other bands could be inhibited by clavulanic acid but not cloxacillin. The 95 kb plasmid was digested with HindIII and a recombinant plasmid pT948 was obtained. The insert was found to contain blaDHA-1, regulatory gene ampR and an insertion element (IS26), which was downstream of blaDHA-1. PCR and DNA sequencing results confirmed that the 95 kb plasmid encoded at least four beta-lactamase genes: blaTEM-1, blaSHV-12), blaCTX-M-3 and blaDHA-1. Epidemiological typing by PFGE of the six clinical isolates of K. pneumoniae demonstrated identical genotypic patterns. In conclusion, all results indicated that the six multi-drug resistant clinical isolates of K. pneumoniae most probably originated from one clone and caused a localized epidemic in the intensive care units.

Anti-Bacterial Agents↗
PubMed1989

[Treatment and surgery of abdominal septic states: comparison of two antibiotic therapies].

A prospective, randomized controlled study was carried out in 104 patients to compare clavulanate-potentiated amoxycillin ('Augmentin') with a combination of cephalosporins (cefazoline and cefadroxil) supplemented with metronidazole in the treatment of abdominal septic states, suspected or proven after surgical intervention. Patients on 'Augmentin' received 1.2 g (1 g amoxycillin plus 200 mg clavulanic acid) intravenously 3-times daily for a mean of 6.6 days, then 375 mg (250 amoxycillin plus 125 mg clavulanic acid) orally for a further 6.4 days. Patients on the standard therapy received 1 g cefazoline intravenously 4-times daily plus 500 mg metronidazole intravenously 3-times daily for 7 days, then 500 mg cefadroxil orally 4-times daily for a mean of 6.6 days. Evaluation of the patients' condition was undertaken after 24 hours, 3 days and 7 days. The results showed a significantly better response to treatment in the 'Augmentin' group, as judged by the amelioration of clinical symptoms, bacteriological findings, and tolerance. All the patients treated with 'Augmentin' showed an excellent or satisfactory overall response at Day 7 compared with 76% of those receiving the standard therapy.

Abdomen↗
PubMed2004

[Amoxicillin in tonsillectomy: preliminary data on the evaluation of serum and tissue concentrations].

Amoxicillin was administered to 50 patients with chronic recurrent tonsillitis waiting for tonsillectomy. Group A (N=16) received 2.2 g of amoxicillin plus clavulanic acid with intravenous injection 10 minutes before tonsillectomy Group B (N=34) was treated with 3 doses of amoxicillin-clavulanic acid administered orally the day before surgery, plus one oral administration 2 hours before tonsillectomy. Antibiotic doses were established on patient's weight using maximum suggested. The measures were, estimated in serum and in tonsils using High Performance Liquid Chromatography, (HPLC). The data show better efficacy of intravenous administration than oral administration.

Administration, Oral↗
PubMed1988

Characterization and comparison of two penicillinase-producing strains of Streptococcus (Enterococcus) faecalis.

We identified two beta-lactamase-positive enterococci. One strain was high-level (MIC, greater than 2,000 microgram/ml) gentamicin resistant; the other was not (MIC, 12.5 microgram/ml). beta-Lactamase production was extrachromosomally mediated in both strains, and both strains showed an inoculum effect reversed by beta-lactamase inhibitors. The strain lacking high-level gentamicin resistance showed synergistic killing with a combination of penicillin, clavulanic acid, and gentamicin.

Ampicillin↗