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PubMed2000

Pharmacokinetics of piperacillan after intramuscular injection in red-tailed hawks (Buteo jamaicensis) and great horned owls (Bubo virginianus).

This study characterized and compared the pharmacokinetics of piperacillin after single 100 mg/kg i.m. injections in nine red-tailed hawks (Buteo jamaicensis) and five great horned owls (Bubo virginianus) over 48 hr by a modified agar well diffusion microbial inhibition assay. The mean maximum plasma piperacillin concentrations were 204 microg/ml and 221 microg/ml for the hawks and owls, respectively, and times of maximum concentrations were 15 min and 30 min, respectively. The calculated mean terminal elimination half-lives were 77 min in the hawks and 118 min in the owls. Area-under-the-curve values were 218 +/- 52 microg x hr/ml in the hawks and 444 +/- 104 microg x hr/ml in the owls. On the basis of the most common minimal inhibitory concentration (90%) for various bacterial isolates from clinical samples of 8 microg/ml, analysis of the data suggests that the maximum dosing interval for piperacillin at 100 mg/kg in medium sized raptors should be 4-6 hr.

Animals↗
PubMed1994

Piperacillin/tazobactam. A review of its antibacterial activity, pharmacokinetic properties and therapeutic potential.

Combining tazobactam, a beta-lactamase inhibitor, with the ureidopenicillin, piperacillin, successfully restores the activity of piperacillin against beta-lactamase-producing bacteria. Tazobactam has inhibitory activity, and therefore protects piperacillin against Richmond and Sykes types II, III, IV and V beta-lactamases, staphylococcal penicillinase and extended-spectrum beta-lactamases. However, tazobactam has only species-specific activity against class I chromosomally-mediated enzymes. Resistant organisms include some Citrobacter spp., Enterobacter spp., Serratia spp., Xanthomonas maltophilia and Enterococcus faecium. Consistent with its in vitro activity, preliminary clinical data indicate that the fixed combination of piperacillin/tazobactam (dose ratio 8:1) is effective in the treatment of moderate to severe polymicrobial infections, including intra-abdominal, skin and soft-tissue and lower respiratory tract infections. In limited comparative trials, piperacillin/tazobactam demonstrated equivalent or better efficacy than standard comparator regimens in these infections. Piperacillin/tazobactam in combination with an aminoglycoside was effective in the empirical treatment of fever in patients with neutropenia and compared favourably with ceftazidime in combination with an aminoglycoside, although second-line therapy with a glycopeptide antibiotic may be indicated in unresponsive episodes. Data from phase III trials indicate that piperacillin/tazobactam has a tolerability profile typical of a penicillin agent. Piperacillin/tazobactam provides a broad spectrum of antibacterial activity in a convenient single formulation suitable for use in the treatment of polymicrobial infections. Possible limitations concern its restricted activity against class I beta-lactamases, enzymes that are becoming increasingly important in the nosocomial environment. Combined therapy with an aminoglycoside may be necessary in more serious infections.

Animals↗
PubMed1992

Pharmacodynamic effects of antibiotics. Studies on bacterial morphology, initial killing, postantibiotic effect and effective regrowth time.

Pharmacodynamics of antibiotics deals with time course of drug activity and mechanisms of action of drugs on bacteria. In this thesis pharmacodynamic parameters have been studied after brief exposure of gram-positive bacteria to daptomycin, imipenem or vancomycin and after short exposure of gram-negative bacteria to amikacin, ampicillin, aztreonam, cefepime, cefotaxime, ceftazidime, ceftriaxone, cefuroxime, imipenem, mecillinam, or piperacillin. The studies have been focused on morphological alterations, initial killing, postantibiotic effect (PAE) and effective regrowth time (ERT) and a method, based on bioluminescence assay of intracellular ATP has been used. The basic principle behind this technique is that ATP in living cells is present in a relatively constant amount, and hence affords a measure of the number of microbial cells. The PAE describes the delayed regrowth of bacteria after brief exposure to antibiotics. The number of cells measured after this antibiotic exposure describes the initial killing and is also the start value for calculating the PAE. PAEs of 2-3 h were obtained by bioluminescence for gram-positive bacteria exposed to imipenem or vancomycin. This is in agreement with results obtained by viable count and is probably due to similar weak initial decrease in cell density when assayed by both methods. Long (greater than 3 h) concentration dependent PAEs and moderate (less than or equal to 1 log10) initial decrease in intracellular ATP were in general seen for gram-positive bacteria exposed to daptomycin and for gram-negative bacteria exposed to imipenem or amikacin when assayed by bioluminescence. These very long PAEs and rather weak initial killing have to be compared with the shorter PAEs and stronger initial killing reported by us and others using viable count. Furthermore, this study showed that there was a relatively good concordance between microscopy and bioluminescence, which are direct methods, in determining the initial killing and PAE of imipenem on Escherichia coli. The ERT, defined as the time for bacterial density to increase 1 log10 from the pre-exposure inoculum, was independent of the method used for measuring regrowth of E. coli after brief exposure to imipenem. The combination of mecillinam with ampicillin, aztreonam, ceftazidime or piperacillin and the combination of amikacin with ceftazidime, ceftriaxone or piperacillin induced longer PAEs on gram-negative bacteria than the sum of PAEs of the individual antibiotics. A strong initial killing in combination with a long PAE cause a long ERT and may allow the antibiotic concentration to stay below MIC during long periods of time without any regrowth. This may, in clinical practice, have implications for long dosing intervals.

Amdinocillin↗
PubMed1988

A double-blind placebo-controlled trial of perioperative prophylactic antibiotics for elective neurosurgery.

In this study, 417 patients undergoing "clean" elective neurosurgical operative procedures were randomized to receive a broad-spectrum antibiotic (piperacillin) or placebo given as three perioperative doses, each 6 hours apart. Randomization was carried out by hospital pharmacists, and the investigators remained blinded until the end of the study. Twenty cases were excluded from analysis because either an unforeseen second operation was performed or antibiotic therapy was initiated within 30 days after surgery to treat infection or the risk of infection. Twelve of the 205 patients treated with placebo developed postoperative wound sepsis, and four of the 192 piperacillin-treated patients developed wound sepsis--a statistically significant difference (p less than 0.05, Fisher's exact test). Piperacillin thus appeared to reduce the incidence of neurosurgical wound infection in this study.

Anti-Bacterial Agents↗
PubMed1989

Comparison of in vitro susceptibilities among gram-negative rods.

The activity of mezlocillin, azlocillin and piperacillin was compared using 100 clinical isolates of gram-negative rods. Overall piperacillin had the highest activity with 72 per cent sensitive strains; mezlocillin, 66 per cent, and azlocillin, 57 per cent. In the group of Pseudomonas aeruginosa, however, mezlocillin showed distinctly lower activity than both piperacillin and azlocillin.

Azlocillin↗
PubMed1989

Studies on the synergism of sulbactam and beta-lactam antibiotics under in vitro conditions and in healthy volunteers after intravenous administration. Antibacterial activity in vitro, compatibility and pharmacokinetics of the drugs in combination.

Sulbactam, a new beta-lactam inhibitor, increased the in vitro activity of cefotaxime, mezlocillin and piperacillin against 803 clinical bacterial isolates. The synergism of sulbactam and these antibiotics was particular marked against 467 beta-lactamase positive strains, both aerobic and anaerobic. In the presence of sulbactam the mean minimal inhibitory concentrations (MICs) of the antibiotics against beta-lactamase positive bacteria were greatly reduced: with cefotaxime by 58%, with mezlocillin by 64% and with piperacillin by 70%. Sulbactam alone at low concentrations inhibited the growth of only a few strains (Neisseria spp., Acinetobacter spp.). The inhibitor proved to be very stable in infusion media under a variety of conditions and was compatible in vitro with 14 different beta-lactam antibiotics. The pharmacokinetics profiles of sulbactam and the antibiotics cefotaxime, mezlocillin and piperacillin were similar after infusion to healthy volunteers. The relevant pharmacokinetic parameters of the single substances were essentially unchanged when administered in combination. The general similarity between the pharmacokinetics of sulbactam and of the beta-lactam antibiotics appears to be an essential precondition for the therapeutic success of such a synergistic combination. Thus the physicochemical and pharmacological properties of sulbactam apparently permit flexible dosage in combination with different penicillins or cephalosporins and sulbactam can be administered as non-fixed combination in the clinical treatment of bacterial infections.

Adult↗
PubMed1987

Antibiotics in infections of the biliary tract.

The combination of a penicillin and an aminoglycoside has been recommended as the initial treatment of choice for patients with infections of the biliary tract. However, elderly, septic, patients with jaundice have a high incidence of renal problems. For this reason, amingolycoside treatment of these patients must be reevaluated as newer less nephrotoxic agents become available. We, therefore, performed a prospective, randomized trial of ampicillin plus tobramycin, cefoperazone and piperacillin in patients with biliary tract infections. During a 20 month period, 106 patients with acute cholecystitis (53) or cholangitis (53), or both, received one of these antibiotic regimens for a minimum of five days. In patients with acute cholecystitis, ampicillin plus tobramycin, cefoperazone and piperacillin had clinical cure rates of 85, 95 and 95 per cent, respectively. In patients with cholangitis, however, cure rates for the three regimens were 85, 56 (p less than 0.05 versus ampicillin plus tobramycin) and 60 per cent (not significant versus ampicillin plus tobramycin), respectively. Moreover, 13 per cent of the patients receiving cefoperazone had an increased prothrombin time and three of 39 patients receiving this antibiotic had clinical problems with bleeding. Nephrotoxicity was greatest in patients with cholangitis receiving ampicillin plus tobramycin, 10 per cent, as compared with 3 per cent in those who did not receive an aminoglycoside. This difference, however, was not statistically significant. It was concluded that piperacillin should be considered for antibiotic management of patients with acute cholecystitis and that further studies are necessary in patients with cholangitis to determine whether or not newer agents should replace penicillin and aminoglycoside combinations.

Ampicillin↗
PubMed1988

Prolonged aqueous humor levels of subconjunctival antibiotics after treatment with acetazolamide and/or timolol.

Many ophthalmologists routinely administer subconjunctival antibiotics at the end of cataract surgery for prophylaxis against bacterial endophthalmitis. Additionally they use acetazolamide and/or timolol to control intraocular pressure in the first 24-hour postoperative period. An animal study was undertaken to learn whether treatment with the aqueous humor suppressants, acetazolamide, and timolol prolongs the concentrations of antibiotics in the aqueous humor after subconjunctival administration of the antibiotic. Treatment with acetazolamide significantly increased concentrations of piperacillin; it had less consistent effects on tobramycin levels. Timolol treatment did not produce increased piperacillin concentrations at six hours; however, concentrations at 12 and 24 hours were significantly higher than in the controls. Timolol treatment increased tobramycin concentrations only at six hours. The combined use of timolol and acetazolamide produced significantly higher concentrations of piperacillin, but not of tobramycin.

Acetazolamide↗
PubMed1994

A multicentre in vitro evaluation of piperacillin/tazobactam in Germany.

In a multicentre study in Germany 10584 fresh clinical aerobic isolates were tested for susceptibility to piperacillin (30 micrograms or 100 micrograms discs) and piperacillin/tazobactam (30 micrograms/10 micrograms or 100 micrograms/10 micrograms discs). Preliminary breakpoints for piperacillin/tazobactam according to the German standard methods (Deutsches Institute für Normung) were: Resistant: inhibition zone < or = 14 mm; MIC > or = 64 mg/l. Susceptible: inhibition zone > or = 22 mm; MIC D or = 4 mg/l. For comparison, the National Committee for Clinical Laboratory Standards (USA) breakpoints for enterobacteria (100/10 micrograms/disc) are: Resistant: inhibition zone < or = 17 mm; MIC > or = 128/4 mg/l. Susceptible: inhibition zone > or = 21 mm; MIC < or = 6/4 mg/l. Using the DIN criteria, 73.2% of Enterobacteriaceae tested were susceptible to piperacillin and 91.2% to piperacillin/tazobactam. Of Staphylococcus aureus strains tested (including methicillin resistant Staphylococcus aureus, MRSA), 20.8% were susceptible to piperacillin and 78.7% to piperacillin/tazobactam. The MIC of piperacillin/tazobactam for most staphylococci and Enterobacteriaceae that had been classified on the first test as having intermediate susceptibility or resistance to piperacillin/tazobactam by DIN criteria were re-evaluated to solve methodological problems and inconsistencies among the participating laboratories. This second study resulted in a reduction of the zone diameter for susceptibility of staphylococci to > 14 mm and found that an additional 55.7% of resistant/intermediate Enterobacteriaceae and 91.0% of resistant/intermediate S aureus were susceptible to piperacillin/tazobactam, giving totals for susceptibility of 96.1% for Enterobacteriaceae and 98.1% for S aureus.

Drug Therapy, Combination↗
PubMed1995

[Piperacilline/tazobactam combination+amikacin versus ceftazidime+amikacin in patients with neutropenia and fever. An open multicenter study. Groupe d'étude des Aplasies Fébriles].

OBJECTIVES: To evaluate the toxicity and effectiveness of piperacillin+tazobactam and amikacin compared with a reference treatment with ceftazidime and amikacin given as first line therapy in neutropenic patients with fever. METHODS: A multicentric randomized trial was conducted in 222 adults who had fever (38 degrees C for > 3 h) during a period of aplasia (white cell count < 0.5.10(9)/l for 22.9 +/- 10.4 days) induced by chemotherapy for acute leukaemia (68.1%) or by bone marrow autograft for lymphoma, myeloma or solid tumour (30.3%). 109 patients were assigned to the piperacillin (12 g/d)/tazobactam (1.5 g/d)+amikacin group and 113 to the ceftazidime (3 g/d)+amikacin group. Evaluation criteria were the frequency of apyrexia after a 72-hour antibiotic regimen and major infectious events defined as death due to infection and severe infections causing a delay in the chemotherapy protocol. RESULTS: Data obtained in 188 patients who fulfilled all the protocol criteria were evaluated. The episode of fever was controlled better with the piperacillin/tazobactam+amikacin combination (apyrexia achieved in 60.6% of the patients vs 44.7% in the ceftazidime+amikacin group, p = 0.028) and there were fewer superinfections (23% vs 41% respectively, p < 0.008). Tolerance was similar in the two groups. In vitro, 56% of the strains resistant to piperacillin and isolated prior to treatment were sensitive to the piperacillin/tazobactam combination. Among the strains isolated (41 Gram-, 61 Gram+), 72% were sensitive to ceftazidime and 84% were sensitive to the piperacillin/tazobactam combination. There were 16 deaths due to infection (8.5%) with no difference according to antibiotic regimen. There was no difference in toxicity. CONCLUSION: Tolerance was similar in the two groups. A combined regimen of piperacillin/tazobactam can be proposed as first line treatment for neutropenic patients with fever.

Adult↗
PubMed1997

Broth disk elution method for anaerobic bacteria: a collaborative study to assess its reliability for clinical purposes.

A collaborative study involving seven laboratories was undertaken to evaluate the reproducibility and the reliability of the broth disk elution test against anaerobic bacteria by comparing with the reference agar dilution method. A two breakpoint broth test was also evaluated. Assays were performed using the same testing conditions (i.e. medium, temperature, atmosphere and incubation time). One hundred Gram-negative and Gram-positive clinical isolates were initially studied. Overall agreement of 98.5% and 97.5%, were found for disk elution and the two breakpoint tests, respectively. In order to assess the reliability of the disk elution test, two different lots (LOT1 and LOT2) of disks of piperacillin and clindamycin were selected, to obtain two final concentrations after dilution (10 and 60 mg/mL; 1 and 4 mg/mL, respectively). Two hundred and eighty assays were performed against one strain of both Bacteroides fragilis(piperacillin MIC, 8.0 mg/mL; clindamycin MIC, <0.5 mg/mL) and Bacteroides thetaiotaomicron(piperacillin MIC, 16.0 mg/mL; clindamycin MIC, <0.5 mg/mL). With LOT 1, considering both species and both antibiotics, the agreement among six laboratories ranged from 85% to 100% (P > 0.05) with the higher concentration. Overall agreement among all laboratories was 91%. No optimal agreement (>90%) for clindamycin-Bacteroides thetaiotaomicron using the LOT1 (77%) was found. Since this finding was not observed with LOT2 (100% agreement), discrepancies were attributed to variation between lots. Overall agreement with LOT2 was 100% for all centres. The present study indicates that the broth disk elution method proved to be a reliable and suitable alternative for routine susceptibility testing for anaerobic bacteria, as a resistance screening method for clinical purposes.

Journal Article↗
PubMedDate not supplied

Susceptibility and tolerance of beta-lactamase-producing, methicillin-sensitive strains of Staphylococcus aureus towards seven broad-spectrum penicillins.

The activity of penicillin G, ampicillin, carbenicillin, ticarcillin, azlocillin, mezlocillin and piperacillin against 102 beta-lactamase-producing, methicillin-sensitive strains of Staphylococcus aureus was determined by agar dilution (method A) and broth microdilution (method B) techniques. By NCCLS breakpoint criteria, 4% of the strains were "sensitive" to penicillin and ampicillin, and almost 100% were "sensitive" to the other drugs when method A was used. Results with method B were only significantly lower as far as the cumulative percentage of strains "sensitive" to azlocillin, mezlocillin and piperacillin was concerned (63-71%). Bactericidal effects at "sensitive" levels were observed in 0-2% (penicillin, ampicillin), 31-35% (carbenicillin, ticarcillin) and 10-14% (azlocillin, mezlocillin, piperacillin). While differences in MIC and MBC levels ranged from 0 to 8 dilution steps, tolerance (a greater than 32-fold difference) was seen in at least 9-22% of all strains (depending on the drug tested); experimental limitations, however, excluded a determination of tolerance in all our strains. In a semi-quantitative nitrocefin assay, "strong" beta-lactamase production was correlated to high MIC and/or MBC levels.

Drug Tolerance↗
PubMed1991

[Progress of antibiotic therapy in pediatrics].

The advances in the antibiotic therapy of acute bacterial infections can be shown by the decreasing frequency of complications and fatalities in children. The annual death-rate from pneumonia in children aged one month to 15 years has fallen in Schleswig-Holstein from 1.8 (1954-1958) to 0.6 per 10,000 (1969-1973). At the same time the total death-rate in the same age group has fallen from 14.5 to 9.3 per 10,000 children. The percentage of pneumonia in the total death-rate was 5.3% in 1971-1973: 1.6% in the first month of life and after the sixteenth year 2.3%. Pneumonia was in fourth place (after accident, malformation and neoplasm) as a cause of death in children more than one month old. Of 245 children operated on for congenital heart disease in 1983-1984, bacterial and fungal infections occurred in 3.6% compared to 17.8% of 469 in 1968-1972. Staphylococcal infections decreased from 3.4% to 0.8% and those caused by gram-negative bacteria from 6.9% to 0. Perioperative prophylaxis was performed with cefotaxime plus piperacillin in 1983-1984 versus oxacillin plus ampicillin in 1968-1972. Between 1984 and 1989, 944 children (premature babies and term babies) were treated in the intensive care unit of the University Children's Hospital of Kiel. The incidence of sepsis was 5% (congenital sepsis 4%, sepsis acquired after birth 1%). Early diagnosis and treatment of severe bacterial infections with cefotaxime plus piperacillin reduced the mortality rate of sepsis to 2%. Sepsis never developed under treatment with cefotaxime plus piperacillin.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Bacterial Agents↗
PubMed1985

Use of discriminative models of Pseudomonas aeruginosa bacteremia in granulocytopenic rats for testing antimicrobial efficacy.

The efficacy of single agent and combination antibiotic therapy was evaluated in rats with severe granulocytopenia and Pseudomonas aeruginosa infection using animal survival, rates of bacteremia and the emergence of resistant organisms as criteria. In this model end points following single agent therapy with imipenem/cilastatin and the synergistic combination of moxalactam plus amikacin were comparable. At a high bacterial challenge dose, equivalent results were obtained using single agent therapy with either piperacillin or ticarcillin. Results were also similar following therapy with piperacillin or ticarcillin in synergistic combination with amikacin. At a lower bacterial challenge dose, aminoglycoside therapy was superior to therapy with the beta-lactams. Therapy with the in vitro synergistic double beta-lactam combination of ceftazidime plus piperacillin was no more effective than therapy with the individual compounds. Results from these studies in this discriminative animal model have in part been used to formulate prospective clinical antibiotic studies in granulocytopenic cancer patients.

Animals↗
PubMed2005

Do antimicrobial susceptibility patterns of colonic isolates of Bacteroides species change after antibiotic prophylaxis with cefoxitine during elective abdominal surgery?

The objectives of the study were to investigate and compare the susceptibility profiles of preoperative and postoperative intestinal Bacteroides fragilis and Bacteroides thetaiotaomicron strains against antimicrobials to evaluate their resistance development patterns due to prophylactic antibiotic administration. Preoperative and postoperative stool samples were obtained from patients undergoing elective abdominal surgery with a "clean-contaminated" wound categorization. All patients received cefoxitin 2 g as prophylaxis. Isolates of Bacteroides species were identified. Susceptibility tests against ampicillin, piperacillin, cefoxitin, clindamycin, chloramphenicol, metronidazole, imipenem, and amoxicillin-clavulanate were performed. Stool samples were collected from 40 patients at two settings: before and after the operation. Most of the patients (53%) were operated on because of colorectal carcinoma and underwent surgery that included colectomy or anterior resection. Bacteroides fragilis and Bacteroides thetaiotaomicron were isolated in both samples obtained from 22 and 34 patients, respectively. In the present study 95% to 100%, 50% to 74%, 46% to 64%, and 18% to 35% of preoperatively isolated Bacteroides species were resistant to ampicillin, cefoxitin, clindamycin, and piperacillin, respectively. Although there were no statistically significant difference, postoperative strains were more resistant than preoperative isolates, and the resistance rates were found to be 95% to 100%, 55% to 82%, 46% to 86%, and 37% to 41%, respectively. Both Bacteroides species isolated from all specimens before and after the surgery were uniformly susceptible to amoxicillin-clavulanate, imipenem, metronidazole, and chloramphenicol.Our data revealed that Bacteroides strains revealed high resistance to ampicillin, cefoxitin, piperacillin, and clindamycin. Metronidazole, imipenem, and amoxicillin-clavulanate seem highly effective against both Bacteroides species. Cefoxitin prophylaxis did not significantly increase the resistance patterns against antimicrobial agents.

Adult↗
PubMed2001

Antimicrobial susceptibility of respiratory isolates of Enterobacteriaceae and Staphylococcus aureus in Italy: incidence and trends over the period 1997-1999.

The antibiotic susceptibility of members of the family Enterobacteriaceae and of Staphylococcus aureus strains isolated from the respiratory tract was assessed over the period 1997-1999 as part of the Italian Epidemiological Observatory survey sponsored by the Smith-Kline Foundation. A standardised method was used to determine the MICs of 22 antibiotics against isolates of Klebsiella pneumoniae (n=870), Escherichia coli (n=684), Enterobacter cloacae (n=342), Enterobacter aerogenes (n=187) and Serratia marcescens (n=135) as well as the MICs of 11 antibiotics against isolates of Staphylococcus aureus (n=1,606). Overall, the susceptibility rate of Enterobacteriaceae isolates was > or = 90% to 5 agents (meropenem, imipenem, amikacin, cefepime and gentamicin); 89-80% to 2 agents (ciprofloxacin and tobramycin); and <80% to 11 agents (cefotaxime, piperacillin-tazobactam, trimethoprim-sulfamethoxazole, cefetamet, ceftriaxone, ceftazidime, aztreonam, ticarcillin-clavulanate, tetracycline, piperacillin, cefuroxime, chloramphenicol, ticarcillin, amoxicillin-clavulanate and amoxicillin). During the 3-year monitoring period, antibiotic susceptibility increased in Klebsiella pneumoniae against amoxicillin-clavulanate, in Escherichia coli against third-generation cephalosporins and aztreonam, in Enterobacter aerogenes against amoxicillin and piperacillin-tazobactam and in Serratia marcescens against most of the antibiotics. In contrast, Enterobacter cloacae showed a tendency to develop resistance to cefetamet, amikacin and ciprofloxacin. Of the total number of Staphylococcus aureus strains, 38% were methicillin resistant. Nearly 80% of the methicillin-resistant strains displayed a multiresistance pattern (additional resistance to 2 or more non-beta-lactam antibiotics). Rates of susceptibility of particular species (Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus) were compared using strains from different geographical areas of Italy (northern, central and southern) and from different nosocomial areas (outpatients, intensive care unit [ICU] inpatients, non-ICU inpatients). Susceptibility of Klebsiella pneumoniae to several antibiotics was lower in southern Italy, whereas the incidence of methicillin-resistant strains was higher in northern and central Italy. The susceptibility of Escherichia coli was similar in all three areas. No significant differences in susceptibility of Klebsiella pneumoniae or Escherichia coli were found between strains from inpatients and outpatients or from inpatients admitted to ICU and non-ICU units. The incidence of methicillin-resistant Staphylococcus aureus was higher in ICU inpatients (52%) than in non-ICU inpatients (38%) and lower in outpatients (19%) than in inpatients.

Drug Resistance, Bacterial↗
PubMed2006

Impact of ceftazidime restriction on gram-negative bacterial resistance in an intensive care unit.

The present study included three periods: (1) a 12-month pre-restriction and control period in 2001; (2) a 12-month restriction period with reduced ceftazidime prescribing in favor of piperacillin-tazobactam (2002); (3) and a 24 month post-restriction period (2003-2004). Note that, for results, P represents the difference between 2002 and 2001; P', the difference between 2003 and 2001; and P'', the difference between 2004 and 2001. No changes in hygiene practices were observed during these three periods. The purpose of this study was to assess the effect of reducing ceftazidime use in an intensive care unit (ICU) upon Gram-negative bacterial resistance, particularly as regards Pseudomonas aeruginosa. During the three periods of the study, patients were similar concerning age, Simplified Acute Physiology Score (SAPSII), the site of nosocomial infection, and the requirements for mechanical ventilation (75% in 2001, 76% in 2002, 74% in 2003, and 85% in 2004). The most commonly isolated pathogens were P. aeruginosa, Acinetobacter baumannii, and Enterobacteriaceae. The use of ceftazidime decreased significantly from 12.6% in 2001 to 9% in 2002, to 3% in 2003 (P' = 0.0009), and 2.6% in 2004 (P'' = 0.0001) in favor of piperacillin-tazobactam (0% 2001 to 3.7% in 2003; P' = 0.002; and 5% in 2004; P'' = 0.0001). Simultaneously, we observed a significant decrease in isolates of P. aeruginosa resistant to piperacillin-tazobactam (P = 0.03; P' = 0.004; P'' = 0.009), and those resistant to imipenem in 2003 (P' = 0.008). We also noted a significant decrease in A. baumannii isolates resistant to ceftazidime (P' = 0.01; P'' = 0.0004) and those resistant to imipenem in both 2002 and 2004 (P = 0.03; P'' = 0.04), and a considerable decrease in isolates of Klebsiella pneumoniae producing expanded spectrum betalactamase (ESBL) in 2003 and 2004 (P' = 0.04; P'' = 6.10(-5)). In contrast, we noted an increase in penicillinase-producing isolates of K. pneumoniae, from 6% in 2001 to 16% in 2002 (p = 0.01), 20% in 2003 (P' = 0.001), and 32% in 2004 (P'' = 10(-6)). We concluded that restriction of ceftazidime use was demonstrated to be efficient in reducing antimicrobial resistance, especially to K. pneumoniae ESBL.

Anti-Bacterial Agents↗
PubMed1984

Unpredictable interactions between cefotetan and penicillins or aminoglycosides.

The bacteriostatic and bactericidal activity of gentamicin, amikacin, piperacillin, azlocillin, ampicillin, benzyl penicillin, and oxacillin against 85 selected isolates was measured alone and in the presence of subinhibitory concentrations of cefotetan. A potential for antagonistic interactions between cefotetan and acylamino penicillins (piperacillin greater than azlocillin greater than ampicillin) were observed with some strains; synergy was suggested with other isolates, however, Bacteriostatic and bactericidal activity of the two aminoglycosides was enhanced by cefotetan with most gram-negative bacilli, but bactericidal activity was significantly diminished with 4 of 65 strains. Piperacillin and cefotetan were clearly antagonistic with 11 of 44 strains and synergistic with 4 of 44 strains of gram-negative bacilli: the remaining 21 strains gave off scale end points and could not be analyzed in that way.

Aminoglycosides↗