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PubMed1997

The use of aztreonam as an alternate therapy for multi-resistant Pseudomonas aeruginosa.

The emergence of multi-resistant Gram-negative bacteria has created a most alarming clinical situation. The armamentarium of antibiotics used against this group of organisms is rapidly being depleted. Our routine therapeutic approach to control and prevent these Gram-negative bacteria from gaining a foothold was the empirical use of an aminoglycoside combined with piperacillin. However, aminoglycoside resistance is now routine rather than unusual. We evaluated the role of the monobactam aztreonam in burn wound infections and compared it to the aminoglycosides amikacin and gentamicin as well as piperacillin for the Enterobacteriacae and Pseudomonas aeruginosa. A total of 1274 Gram-negative isolates including P. aeruginosa were evaluated for susceptibility to the above-mentioned antibiotics from January 1995 to August 1995 (Table I). Among the Enterobacteriacae, aztreonam was more effective than amikacin and piperacillin (58.4 per cent vs. 45.8 per cent, respectively). However, it still fluctuated among the Enterobacteriacae as did the aminoglycosides. One major significant finding was that while susceptibility to aztreonam was variable for the Enterobacteriacae, P. aeruginosa remained 90 per cent susceptible to aztreonam and 90 per cent susceptible to piperacillin, whereas it was 79 per cent resistant to the aminoglycosides. Consequently, when choosing an antimicrobial in a suspected P. aeruginosa burn wound infection, aztreonam and piperacillin should be considered as the first line of defense.

Aminoglycosides↗

PubMed1983

Alternative antibiotics for the treatment of Pseudomonas infections in cystic fibrosis.

We have investigated the effectiveness of seven new beta-lactam antibiotics, azlocillin, piperacillin, ceftazidime, cefsulodin, cefoperazone, latamoxef (moxalactam), and cefotaxime, against acute pulmonary exacerbations caused by Pseudomonas aeruginosa in cystic fibrosis. Three hundred and fifty-five strains of Ps aeruginosa isolated from 310 sputum cultures (190 cystic fibrosis patients) were tested for susceptibility to the drugs by determination of minimal inhibitory concentrations (MIC). The highest activity was shown by ceftazidime (6% resistant strains) followed by cefsulodin and piperacillin (15 and 16% resistant strains); very low activity was found for cefotaxime and latamoxef (moxalactam). Ceftazidime was the most active drug against 32 pseudomonas isolates that were resistant to both carbenicillin and aminoglycosides (78% susceptible). A randomized, double-blind trial of azlocillin, piperacillin, ceftazidime, cefsulodin or cefoperazone was performed in 111 cystic fibrosis patients with predominant and susceptible pseudomonas in their sputum. Results were evaluated by a clinical, radiological and bacteriological scoring system: the best results were obtained with ceftazidime, followed by cefsulodin and piperacillin. However, pseudomonas was eradicated in only 22 (23%) of the cases with the most active drugs and persisted or reappeared in all the cases 1 to 3 months later. Ceftazidime always eradicated Staph. aureus and Haemophilus influenzae associated with pseudomonas. Similar eradication occurred nearly always with cefsulodin but rarely with the other drugs. No serious drug reaction occurred but a later fever and rash with piperacillin, transient diarrhoea with cefoperazone, vomiting with cefsulodin, and very frequent eosinophilia with ceftazidime should be mentioned. These five drugs offer, in varying degree, alternatives to traditional anti pseudomonas antibiotics in cystic fibrosis pulmonary infections, but they should be used only against well-proven resistant strains. Ceftazidime is best and cefotaxime and latamoxef (moxalactam) least useful.

Adolescent↗

PubMed1997

Potentiation of beta-lactams against Pseudomonas aeruginosa strains by Ro 48-1256, a bridged monobactam inhibitor of AmpC beta-lactamases.

Ro 48-1256 is a bridged monobactam inhibitor of Class C beta-lactamases, without significant antibacterial activity of its own. It was tested in combination with imipenem, meropenem, piperacillin and ceftazidime against Pseudomonas aeruginosa isolates, mutants and transconjugants. Imipenem was potentiated against all strains where the AmpC enzyme was inducible or derepressed, with its MICs being reduced from 1-2 mg/L to 0.25-0.5 mg/L for most isolates and from 8-16 mg/L to 1-2 mg/L for those lacking OprD (D2 porin). Ro 48-1256 also abolished in-vitro selection of OprD-deficient mutants by imipenem. Ceftazidime and piperacillin were potentiated against strains derepressed for AmpC enzyme, but not against those where the enzyme remained inducible. For over 90% of AmpC-derepressed organisms, the MICs of ceftazidime were reduced to < or = 8 mg/L by Ro 48-1256 (4 mg/L) and those of piperacillin were reduced to < or = 16 mg/L. Meropenem, which is very stable to AmpC, was not potentiated. Ro 48-1256 did not potentiate piperacillin, ceftazidime or carbapenems when resistance was mediated by Class A, B or D enzymes. Tazobactam, tested as control, had opposite behaviour to Ro 48-1256, potentiating beta-lactams when resistance was due to Class A beta-lactamases but failing to reverse resistance mediated by AmpC. Ro 48-1256 could be used with imipenem to overcome resistance mediated by loss of OprD, or with ceftazidime or piperacillin to overcome derepression of AmpC.

Anti-Bacterial Agents↗

PubMed2001

Elimination of the piperacillin/tazobactam combination during continuous venovenous haemofiltration and haemodiafiltration in patients with acute renal failure.

The elimination of the piperacillin/tazobactam combination was studied in six patients with acute renal failure undergoing either continuous venovenous haemofiltration (CVVH) or continuous venovenous haemodiafiltration (CVVHDF) at 1 L/h and 2 L/h for 12 h. Piperacillin 4 g/tazobactam 0.5 g was given iv on three successive treatment periods and their concentrations in plasma, ultrafiltrate/dialysate and urine were determined for 12 h after each dose. The elimination half-life of piperacillin during CVVH (7.7 +/- 2.3 h; mean +/- s.d.) was significantly longer than during CVVHDF 1 L/h (6.7 +/- 1.9 h) or 2 L/h (6.1 +/- 2.0 h) (P< 0.05). Corresponding values for tazobactam were 13.9 +/- 3.9, 11.6 +/- 3.3 and 9.4 +/- 2.4 h, respectively (P< 0.05). Total piperacillin clearance during CVVH (3.89 +/- 1.23 L/h) was significantly lower than during CVVHDF 1 L/h (5.06 +/- 1.68 L/h) or 2 L/h (5.48 +/- 2.11 L/h) (P< 0.05). The corresponding tazobactam clearance values were 2.42 +/- 0.75, 3.13 +/- 0.66 and 3.75 +/- 1.43 L/h, respectively. The mean 12 h elimination of piperacillin and tazobactam in ultrafiltrate/dialysate was 29% and 37% during CVVH, 42% and 57% during CVVHDF (1 L/h), and 46% and 69% during CVVHDF (2 L/h). We recommend 8 hourly dosing of patients with renal failure on CVVH or CVVHDF with dialysis flow rates of 1 or 2 L/h treated with piperacillin 4 g/tazobactam 0.5 g.

Acute Kidney Injury↗

PubMed1995

Therapeutic regimens in acute experimental pancreatitis in rats: effects of a protease inhibitor, a beta-agonist, and antibiotics.

The osmolality of contrast injected retrograde into the rat pancreatic duct did not affect the severity of the pancreatitis (Urografin, 1,300 mOsm/kg, and Hexabrix, 580 mOsm/kg). The severity of the pancreatitis induced in rats was assessed by survival rate, histologic grading, wet lung ratio, and serum levels of amylase, lipase, and trypsin-like activity. Rats with pancreatitis induced by retrograde injected Urografin, lipopolysaccharide, taurocholic acid plus enterokinase were treated with either intravenous (i.v.) FUT-175 (Nafamstat Mesilate), FUT-175 administered by retrograde pancreatic injection, i.v. terbutaline, i.v. piperacillin sodium, piperacillin sodium by retrograde pancreatic duct injection, or a combination of FUT-175 plus terbutaline and piperacillin. Survival among the rats was increased and the incidence of pancreatic infection reduced in rats treated with i.v. piperacillin or with a combination of FUT-175 plus i.v. terbutaline, plus i.v. piperacillin compared to controls.

Acute Disease↗

PubMed2006

Amphibian peptides prevent endotoxemia and bacterial translocation in bile duct-ligated rats.

OBJECTIVE: To investigate the efficacy of amphibian antimicrobial peptides in preventing bacterial translocation and neutralizing endotoxins in bile duct-ligated rats. DESIGN: Prospective, randomized, controlled animal study. SETTING: Research laboratory in a university hospital. SUBJECTS: Adult male Wistar rats. INTERVENTIONS: Adult male Wistar rats underwent sham operation or bile duct ligation (BDL). Eight groups were studied: sham operation with saline treatment, sham operation with 120 mg/kg tazobactam-piperacillin, sham operation with 2 mg/kg uperin 3.6, sham operation with 2 mg/kg magainin2, BDL with saline treatment, BDL with 120 mg/kg tazobactam-piperacillin, BDL with 2 mg/kg uperin 3.6, and BDL with 2 mg/kg magainin2. MEASUREMENTS AND MAIN RESULTS: Main outcome measures were: endotoxin and tumor necrosis factor-alpha concentrations in plasma and evidence of bacterial translocation in blood, peritoneum, liver, and mesenteric lymph nodes. Endotoxin and tumor necrosis factor-alpha plasma levels were significantly higher in BDL rats compared with sham-operated animals. All amphibian peptides achieved a significant reduction of plasma endotoxin and tumor necrosis factor-alpha concentration when compared with saline- and tazobactam-piperacillin-treated groups. On the other hand, both tazobactam-piperacillin and peptides significantly reduced bacterial growth compared with the control. Tazobactam-piperacillin and magainin2 exerted the maximal inhibition of bacterial growth. CONCLUSION: In conclusion, because of their multifunctional properties, amphibian peptides could be interesting compounds to inhibit bacterial translocation and endotoxin release in obstructive jaundice.

Amphibian Proteins↗

PubMed1987

Serum bactericidal rate as measure of antibiotic interactions.

The serum bactericidal rate (SBR) assay was used to assess the antipseudomonal activity of gentamicin with or without piperacillin. Heat-inactivated donor serum was spiked with gentamicin, piperacillin, or a combination at concentrations representative of levels in serum and tested against five P. aeruginosa strains isolated from blood. The SBR assay was performed as follows: colony counts in test samples (control, gentamicin, piperacillin, and combination) were determined at 0, 2, 4, 6, and 8 h after inoculation of a test strain. Log10 CFU per milliliter was plotted versus time, and linear regression analysis was performed; the slope of the regression line was defined as the SBR. The SBRs of agents alone and in combination were compared statistically. The SBR of gentamicin was dependent on the serum concentration. The combination of gentamicin and piperacillin always resulted in a higher SBR than did either drug alone. However, this difference was not statistically significant for highly gentamicin-susceptible strains (MIC, less than or equal to 2 micrograms/ml) until the gentamicin concentration was reduced below the MIC. For a gentamicin-resistant strain (MIC, 8 micrograms/ml), the combination of gentamicin and piperacillin produced mean SBRs similar to that found with gentamicin-susceptible strains. These results provide evidence that the SBR assay may be a useful method of evaluating antibiotic interactions, since it can be done by using serum and since it compares the antibacterial activity of drugs statistically rather than requiring arbitrary criteria to define interactions.

Analysis of Variance↗

PubMed1996

Penicillin-binding proteins 2b and 2x of Streptococcus pneumoniae are primary resistance determinants for different classes of beta-lactam antibiotics.

High-level resistance to beta-lactam antibiotics in Streptococcus pneumoniae is mediated by successive alterations in essential penicillin-binding proteins (PBPs). In the present work, single amino acid changes in S. pneumoniae PBP 2x and PBP 2b that result in reduced affinity for the antibiotic and that confer first-level beta-lactam resistance are defined. Point mutations in the PBP genes were generated by PCR-derived mutagenesis. Those conferring maximal resistance to either cefotaxime (pbp2x) or piperacillin (pbp2b) were obtained after transformation of the susceptible laboratory strain R6 with the PCR-amplified PBP genes and selection on agar with various concentrations of the antibiotic. In the case of PBP 2x, transformants for which the cefotaxime MIC was 0.16 microgram/ml contained the substitution of a Thr for an Ala at position 550 (Thr550-->Ala), close to the PBP homology box Lys547SerGly, a mutation frequently observed in laboratory mutants and in a high-level cefotaxime-resistant clinical isolate as well. After further selection, transformants resisting 0.3 microgram of cefotaxime per ml were obtained; they contained the substitution Gly550 as the result of two mutations in the same codon. In PBP 2b, Thr446-->Ala, adjacent to another homology box Ser443SerAsn, was the mutation selected with piperacillin. This substitution has been described in all clinical isolates with a low-affinity PBP 2b but was distinct from point mutations found in laboratory mutants. Both pbp2b with the single mutation and a mosaic pbp2b of a clinical isolate conferred a twofold increase in piperacillin resistance. Attempts to select PBP 2b variants at higher piperacillin concentrations were unsuccessful. The mutated PBP 2b also markedly reduced the lytic response to piperacillin, suggesting that such a mutation is an important step in resistance development in clinical isolates.

Amino Acid Sequence↗

PubMedDate not supplied

Antibiotic prophylaxis for biliary tract surgery: selection of patient and agent.

One hundred and three patients undergoing biliary surgery have been entered in a randomized prospective trial for antibiotic prophylaxis. Fifty six received piperacillin (2 gr) and 47 tobramycin (100 mg). Cultures were taken from bile at operation and a clinical and microbiological assessment for infection was carried out postoperatively. Overall infection rate was significantly lower in the piperacillin group (P less than 0.05). The positive bile culture and wound infection rates were also lower in the piperacillin group, though this did not reach statistical significance. Anaerobic bacteria (three patients) and Streptococcus faecalis (one patient) were isolated in the tobramycin group. Overall postoperative infection rate was similar in patients with risk factors for infection and in those without. In conclusion, piperacillin did not significantly improve bile and wound infection rates compared to tobramycin. However piperacillin showed a more appropriate spectrum of activity. Antibiotic prophylaxis is suggested for all patients undergoing biliary surgery.

Bile↗

PubMed1991

Sulbactam/ampicillin combination in the treatment of acute and chronic lower respiratory infections.

The clinical and bacteriological efficacy of a sulbactam/ampicillin combination was compared with piperacillin in a group of 50 patients suffering from acute or chronic lower respiratory infections: 26 were treated intravenously with piperacillin and 24 with sulbactam/ampicillin. The treatment was continued for at least 7 days for 24 patients at the dosage of 3 g sulbactam/ampicillin twice daily, for a further 24 patients at the dosage of 6 g piperacillin twice daily and for two patients at the dosage of 8 g piperacillin twice daily. In the patients treated with sulbactam/ampicillin, a rapid decrease in the fever with the concomitant reduction in cough and sputum production was observed, with cure in 18 cases and improvement in six. In the patients treated with piperacillin cure was observed in 14 cases and improvement in 12 cases. In both treatment groups safety was excellent. There was no significant difference, either in effectiveness or tolerability, between the two groups.

Adolescent↗

PubMed1990

[Comparative study of 2 protocols for antibiotic therapy. Maternal-fetal non-specific bacterial infections during labor].

Two protocols for prophylaxis by antibiotics in labour were compared to see how effective they were in preventing materno-fetal infection in patients who had signs of chorio-amnionitis. There was in increase in E. coli infections in 40% of liquor which were resistant to amoxycillin which had been used right up to now. 135 cases of patients who had received antibiotic treatment in labour were studied. 61 of these were treated with amoxycillin and 74 with piperacillin. The results show that there was a drop of 11.05% in the number of newborns who were infected in the group of patients who were treated with piperacillin. It was not possible using piperacillin to avoid all infections of the mother and fetus. The severity of the infection in the fetus, as judged by the Apgar score and the opinion of the paediatricians, was less serious in the group that was treated with piperacillin. The death rate for both groups was identical: one in each group. Both were caused by E. coli infections. A drop of 11% in post partum maternal infections was noted. Its was shown that piperacillin was more efficacious, but this way of preventing of infections in the mother and fetus lay in finding as early as possible the situation that could increase the risk of infection.

Amoxicillin↗

PubMed1990

Procedural compliance and clinical outcome associated with therapeutic interchange of extended-spectrum penicillins.

The degree of procedural compliance and the clinical outcome associated with a therapeutic interchange of extended-spectrum penicillins were assessed. Pharmacists conducted a concurrent chart review on all patients receiving mezlocillin as a therapeutic alternative for piperacillin or ticarcillin over a five-month period. The pharmacists assessed whether (1) the pharmacy appropriately dispensed mezlocillin when orders were written for piperacillin or ticarcillin, (2) physicians and nurses were properly notified of the therapeutic interchange, and (3) the bacterial isolates were susceptible to mezlocillin. Pharmacists and physicians evaluated clinical outcomes of all patients receiving mezlocillin through a retrospective chart review and classified the responses as "success," "failure," or "indeterminate." Fifty-one orders for piperacillin were written during the study period, and mezlocillin was selected as a therapeutic alternative in all cases. No orders for ticarcillin were written. Proper notification was made to nurses and physicians in 98% and 65% of cases, respectively. No mezlocillin-resistant gram-negative bacteria were found. Eighty-three courses of therapy were reviewed for clinical outcome; 68 were classified as successes, 0 were failures, and 15 were indeterminate. The cost savings after nine months of therapeutic interchange of mezlocillin for piperacillin was $6600. This study indicates that the pharmacy made a proper therapeutic interchange of mezlocillin for piperacillin and followed the correct procedure for notification of the nursing staff. However, more effort is needed to ensure communication with the prescribing physicians.

Bacteria↗

PubMed1985

Respiratory infections: clinical evaluation.

A review of clinical studies of piperacillin shows that it is valuable for the treatment of respiratory infections due to Enterobacteriaceae, Pseudomonas sp, anaerobes, and mixed flora including anaerobes. Various studies of a total of 420 patients treated with piperacillin for lower respiratory tract infections found that 97% of the patients were cured or markedly improved. Piperacillin has also been found as effective as combination therapy (gentamicin or tobramycin plus carbenicillin or ticarcillin) in the treatment of serious infections, including pneumonia and several caused by gram-negative organisms and anaerobic organisms. A review of the literature on bacteriological responses to piperacillin shows that 126 of 153 (82%) of the susceptible strains could be eradicated. Streptococcus pneumoniae, beta-hemolytic streptococci, Haemophilus influenzae, Peptostreptococcus sp, Bacteroides sp, and Fusobacterium sp have been completely eradicated by treatment with piperacillin. Most of the published studies indicate that therapy with the drug is usually well tolerated.

Amikacin↗

PubMed1982

Comparative in vitro antibacterial activity of seven semi-synthetic penicillins against aerobic gram-negative bacteria and enterococci.

The MICs and MBCs of mecillinam, ticarcillin, mezlocillin, azlocillin and piperacillin were determined by the microdilution method in liquid medium using 700 strains of gram-negative bacilli and enterococci isolated from pathological sources and classified as a function of their sensitivity to ampicillin and carbenicillin. The ampicillin and carbenicillin-sensitive strains were generally sensitive to the other penicillins, although there were differences in activity. The ampicillin and carbenicillin-resistant strains of Escherichia coli that produce a TEM-type penicillinase were sensitive to mecillinam. Mezlocillin, piperacillin and azlocillin had MICs of between 32 and 64 mg/l for 40% of these strains. The Klebsiella strains, whose broad-spectrum penicillinase deactivates ampicillin and carbenicillin, remained sensitive to mecillinam. Mezlocillin, azlocillin and piperacillin had MICs of less than 8 mg/l for 50% of these strains. The carbenicillin-resistant strains of Enterobacter and Citrobacter were also resistant to the other penicillins. Piperacillin and mezlocillin displayed some activity against certain strains of carbenicillin-resistant Serratia, Proteus and Acinetobacter. Azlocillin, piperacillin and, to a lesser degree, mezlocillin were active against the strains of Pseudomonas, for which carbenicillin had an MIC of about 512 mg/l. Ampicillin, mezlocillin and azlocillin showed the best activity against the enterococci, against which mecillinam was inactive. The MBC of these antibiotics is greatly influenced by the density of the bacterial inoculum.

Gram-Negative Aerobic Bacteria↗

PubMed1994

Evolution of beta-lactamase inhibitors.

beta-Lactamases present the greatest single challenge to beta-lactam antibiotics, including piperacillin. beta-Lactamase-mediated resistance to supposedly beta-lactamase stable agents such as second- and third-generation cephalosporins is now emerging and inhibitor combinations provide an alternative strategy to overcome this problem. The success of this strategy depends on 1) how efficiently the inhibitor inhibits important beta-lactamases, 2) on how much beta-lactamase the bacteria produce, 3) on the drug that is to be protected, 4) on the permeability and intrinsic susceptibility of the organisms and 5) on the conditions, notably the pH. Tazobactam inhibits most of the clinically important beta-lactamases that give piperacillin resistance, except for the Class I types. Piperacillin itself is a relatively easy drug to protect, particularly against the TEM-type enzymes. The result is that tazobactam greatly extends the activity of piperacillin, notably against enterobacteria, but also against staphylococci and anaerobes. The survey confirmed the very broad spectrum of activity of piperacillin/tazobactam. Resistance occurred in about 17% of the Enterobacter, Citrobacter, Serratia group, where we believe it to have been caused by derepressed Class I enzymes since these strains were cross-resistant to third-generation cephalosporins. Otherwise, resistance was largely confined to such organisms as E. faecium and methicillin-resistant staphylococci, which have piperacillin insensitive penicillin-binding proteins. Finally, some question remains on the antistaphylococcal activity of piperacillin/tazobactam, where MIC tests gave a more favorable impression than disc tests. Nevertheless, early clinical results against staphylococcal infection appear good, with a response rate of nearly 90% [15].

Anti-Bacterial Agents↗

PubMed1982

Sensitivity of 341 non-fermentative gram-negative bacteria to seven beta-lactam antibiotics.

Susceptibility of 341 isolates of non-fermentative gram-negative bacteria to carbenicillin, piperacillin, cefoperazone, moxalactam, cefotaxime, ceftizoxime, and N-formimidoyl thienamycin was determined by the agar dilution and disc diffusion methods. Piperacillin was the most active agent against Pseudomonas aeruginosa, thienamycin the most active against Pseudomonas fluorescens and Pseudomonas putida, and moxalactam the most active against Pseudomonas maltophilia. Piperacillin and thienamycin were the most active agents against the other Pseudomonas species studied. Thienamycin proved to have excellent activity against Acinetobacter calcoaceticus--90% of strains were inhibited by less than or equal to 1 microgram/ml. The two most active drugs against Alcaligenes species were piperacillin and thienamycin, both of which inhibited 90% of isolates at a concentration of 2 micrograms/ml. All drugs were active against Moraxella species. The broad sensitivity spectrum of piperacillin, thienamycin, and the third-generation cephalosporins against non-fermentative gram-negative bacteria indicates their potential use in infections caused by these organisms.

Acinetobacter↗

PubMed1985

Apalcillin [PC-904]: spectrum of activity and beta-lactamase hydrolysis/inhibition.

Apalcillin is a Pseudomonas-active penicillin with a broad spectrum of antibacterial activity similar to that of piperacillin, except for the greater potency of apalcillin against Acinetobacter spp. and Pseudomonas aeruginosa. Studies with 846 isolates representative of the common bacterial pathogens compared apalcillin to piperacillin, azlocillin, mezlocillin, carbenicillin, ticarcillin, cefotaxime, and cefoperazone. Apalcillin and piperacillin were both active against all 13 species of the Enterobacteriaceae that were tested (MIC 50s less than or equal to 8.0 micrograms/ml) but some strains were resistant to both penicillins. Apalcillin was active against Pseudomonas aeruginosa and Acinetobacter spp. (MIC 50 less than 2.0 micrograms/ml). Like other penicillins, apalcillin was not effective against beta-lactamase-producing Staphylococcus spp., Haemophilus spp. or Neisseria gonorrhoeae. Rates of hydrolysis by six beta-lactamase preparations from gram-negative bacilli were determined, comparing apalcillin, piperacillin, azlocillin, ticarcillin, ampicillin and dicloxacillin to benzyl penicillin. Apalcillin and ticarcillin were more resistant than piperacillin and azlocillin to hydrolysis by the PSE-2 enzyme from P. aeruginosa. As did many other penicillins, apalcillin inhibited the Type 1 beta-lactamase that is produced by Enterobacter cloacae. The other enzymes were inhibitory only in very high concentrations.

Ampicillin↗

PubMed1994

Comparison of the E-test and conventional agar dilution methods for susceptibility testing of gram-negative anaerobic rods.

The E test was used to determine the susceptibility of 209 anaerobic Gram-negative rods to ampicillin, amoxicillin-clavulanate, ticarcillin, ticarcillin-clavulanate, piperacillin, piperacillin-tazobactam, clindamycin, chloramphenicol, and cefoxitin. Minimum inhibitory (MICs) were read where growth intersected the strips or where the upper indentation intersected the strips for beta-lactamase inhibitor-containing strips. Reference MICs were performed by the National Committee for Clinical Laboratory Standards agar dilution method. Organisms tested consisted of 117 Bacteroides fragilis group, 24 fusobacteria, and 68 other species (mainly Prevotella species). Agreement of MICs by both methods occurred in 33.4% of cases; 80.8% were within one, 99.0% were within two, and 99.95% were within three doubling dilutions apart. E-test results, expressed as MIC50/MIC90 values (microgram/ml), were as follows: ampicillin: 16/> 256; amoxicillin-clavulanate (2:1), 0.5/4; ticarcillin, 16/> 256; tircarcillin-clavulanate (2 micrograms/ml), 0.5/4; piperacillin, 16/> 256; piperacillin-tazobactam (4 micrograms/ml), 1/8; piperacillin-tazobactam (8:1), 2/8; cefoxitin, 8/64; clindamycin, 0.25/4; and chloramphenicol, 2/8. Conventional MIC methodology yielded MIC50s and MIC90s either identical to, or within one doubling dilution of, E-test results. Percentages of strains susceptible varied by < 3% between the two methods, except for cefoxitin (E test 5.2% lower). Based on these results, the E test is an accurate and practical method for use with the agents and organisms evaluated.

Agar↗