Activity Of Cefpirome Research Articles

Widespread resistance to new antimicrobials in a university hospital before clinical use

The activity of cefpirome, cefepime and piperacillin/tazobactam previously unused in the hospital was evaluated in parallel with five broad-spectrum antibiotics (ceftazidime, ceftriaxone, imipenem, ciprofloxacin and amikacin) currently being used to treat serious infections in the National University Hospital, Singapore. Two hundred and two clinically significant, organisms consecutively isolated during 1998 were included in the study. In vitro efficacy of cefepime, cefpirome and piperacillin/tazobactam was not superior to imipenem, ciprofloxacin and amikacin which are currently used. More than 40% of Enterbacteriaceae were found to be ESBL producers. The incidence of nosocomial organisms resistant to drugs used in serious infections had increased since 1995. Imipenem-resistance occurred in 34.4% of Acinetobacter spp. and 19.2% Pseudomonas aeruginosa. No single agent appeared to be suitable for empirical monotherapy of serious sepsis.

Bacterial isolates from hematology, oncology, and intensive care units: Susceptibility to cefpirome and other beta-lactam antibiotics in a multicenter study in Mexico

Abstract An in vitro multicenter study was conducted in 15 Mexican hospitals from September 1995 to May 1996 to provide data on the prevalence of bacterial isolates from patients in hematology, oncology, and intensive care units, as well as data on the sensitivity of these organisms to cefpirome and other antimicrobial drugs commonly used in these units. Each participating center collected an average of 100 aerobic bacterial isolates from significant clinical specimens. Minimum inhibitory concentrations to cefpirome and 7 other betalactam antibiotics commonly used empirically to treat nosocomial infections in critically ill patients were determined by the microdilution method. The most frequent sources of the isolates were blood (37.1%), bronchoalveolar lavage fluid (16.8%), skin or wounds (15.8%), and urine (14.0%). The isolated bacteria were distributed as follows: gram-negative enteric bacilli (40.8%), gram-negative nonenteric bacilli (38.8%), and gram-positive cocci (20.4%). Multiresistant gram-negative enteric and nonenteric bacilli were the most important pathogens isolated in hospitalized, critically ill patients; however, gram-positive cocci (both staphylococcus and enterococcus) accounted for 20.4% of the isolates. Although the activity of cefpirome was similar or superior to that of the other antibiotics tested in this study, our results clearly stress the need for antimicrobial agents that are effective against infections caused by gram-negative and gram-positive bacteria in critically ill patients.

In Vitro Bactericidal Activity of Cefpirome in Combination with Vancomycin against Staphylococcus aureus and Coagulase-negative Staphylococcus

In Vitro Bactericidal Activity of Cefpirome in Combination with Vancomycin against Staphylococcus aureus and Coagulase-negative Staphylococcus

Comparative in-vitro activity of cefpirome against isolates from intensive care and haematology/oncology units. Belgian Multicentre Study Group.

The susceptibility of 389 Enterobacteriaceae, 231 other Gram-negative bacilli (including 150 Pseudomonas aeruginosa) and 233 Gram-positive organisms was determined by the NCCLS reference microdilution technique against cefpirome and other antibiotics. Cefpirome and cefepime were the most active compounds against Enterobacteriaceae, including potentially beta-lactamase-inducible species. The MIC90 of cefpirome against potentially inducible and non-inducible species of Enterobacteriaceae was 2 mg/L and 0.5 mg/L, respectively. Ceftazidime, cefpirome and cefepime had similar activity against P. aeruginosa, with MIC90s of 64 mg/L, 64 mg/L and 32 mg/L, respectively. Cefpirome and cefepime had similar activity against Gram-positive cocci, with MIC90s of 1 mg/L and 2 mg/L, respectively, against oxacillin-susceptible Staphylococcus aureus and 64 mg/L and 128 mg/L, respectively, against Enterococcus spp.; both had an MIC90 of 1 mg/L against Streptococcus pneumoniae. This study shows that fourth-generation cephalosporins, such as cefpirome, could be useful in haematology/oncology units and, in particular, ICUs where high resistance rates are observed.

In vitro activity of cefpirome against microorganisms isolated in haematology, oncology and intensive care units in Switzerland.

The in vitro activity of cefpirome, a new parenteral fourth-generation cephalosporin, was investigated in the 5 university hospitals of Switzerland, and compared to 9 other antibiotics mainly used in hospitals, such as ceftazidime, ceftriaxone, cefotaxime, piperacillin, imipenem, gentamicin, vancomycin, ciprofloxacin and ofloxacin. A total number of 992 strains collected only from intensive care units and haematology-oncology units were tested by microdilution according to NCCLS. Cefpirome showed an excellent activity against all Enterobacteriaceae (MIC90 = 4 mg/l), methicillin-susceptible staphylococci (MIC90 = 1 mg/l), Streptococcus pneumoniae (MIC90 = 0.25 mg/l) and Haemophilus influenzae (MIC90 = 0.12 mg/l) isolates. Its activity was superior to that of third-generation cephalosporins against cephalosporinase-depressed mutants of Enterobacter cloacae and Citrobacter freundii isolates (MIC90 > 32 mg/l for third-generation cephalosporins vs 4 mg/l for cefpirome). The MICs of cefpirome of 3 strains of Klebsiella spp. with an extended-spectrum-beta-lactamase were lower (MIC90 = 2 mg/l) than those of third-generation cephalosporins (MICs90 > 32 mg/l). Against Pseudomonas aeruginosa cefpirome was as active as ceftazidime. The activity of cefpirome was poor against methicillin-resistant staphylococci, enterococci and nosocomial Gram-negative bacteria such as Stenotrophomonas maltophilia.

In-vitro bactericidal activity of cefpirome in combination with vancomycin against Staphylococcus aureus and coagulase-negative staphylococci.

In an in-vitro study of the bactericidal activity of cefpirome in combination with vancomycin against 11 clinical isolates of staphylococci, cefpirome at a concentration of 0.25 times the MIC acted synergistically with vancomycin (at a concentration of 0.5, 1 or 2 times the MIC) against Staphylococcus aureus and coagulase-negative staphylococci susceptible or resistant to methicillin. Moreover, increasing the cefpirome concentration to 0.5 or 1 times the MIC combined with vancomycin at the same concentration (0.5 or 1 times the MIC) improved the bacterial killing rate; a bactericidal effect was obtained in 9 or 24 h instead of in 24 or 48 h, respectively.

Combination effect of vancomycin and cefpirome against methicillin-resistant Staphylococcus aureus in vitro--antimicrobial activities in postantibiotic phase

The antimicrobial activities of vancomycin (VCM) or cefpirome (CPR) at sub- and above-MICs against clinical strains of methicillin-resistant Staphylococcus aureus (MRSA) during the postantibiotic phase (PAE-phase) induced by CPR or VCM were examined. Antimicrobial activities were determined growth suppression (post antibiotic sub-MIC effect: PA SME) at sub-MICs, and bactericidal activity at sub- and above-MICs. During the PAE-phase induced by VCM, growth suppression and bactericidal activity of CPR were enhanced at sub-MICs, compared with the non PAE-phase. On the other hand, during the PAE-phase induced by CPR, not only were growth suppression and bactericidal activity of VCM enhanced at sub-MICs, but bactericidal activity were enhanced at above-MICs compared with non PAE-phase. These suggest that enhancement of growth suppression and bactericidal activity during PAE-phase was a factor of combination effect of VCM and CPR against MRSA.

In vitro activity of cefpirome against selected clinical enterobacterial isolates with beta-lactamase-mediated resistance.

Previous studies have shown that there is a high incidence of resistance to cephalosporins among enterobacteria isolated in Greek hospitals. This resistance is mainly due to either the derepression of chromosomal cephalosporinases or the acquisition of plasmids coding for SHV-5 type beta-lactamase. In the present study the activity of cefpirome against a number of enterobacteria (Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Enterobacter aerogenes and Serratia marcescens) possessing the mechanisms mentioned above was examined. Cefpirome was found active against all the strains characterized by stable derepression of chromosomal class-C enzymes. The antibiotic was less potent against strains expressing SHV-5 type beta-lactamase due to its hydrolysis by the enzyme. Also cefpirome exhibited good activity against E. aerogenes strains with reduced susceptibility to imipenem. These in vitro data suggest that cefpirome might be useful in treating infections caused by these resistant microorganisms that are frequently encountered in Greek hospitals.

The activity of cefpirome and ten other antibacterial agents against 2858 clinical isolates collected from 20 centres.

Two thousand eight hundred and fifty-eight aerobic clinical isolates of Enterobacteriaceae, Pseudomonas species, staphylococci, streptococci and Haemophilus species were collected in 19 geographically separated centres in the UK and one in Ireland. The identity of each isolate was confirmed at Southmead Hospital and the MIC of cefpirome, cefotaxime, ceftazidime, cefuroxime, cephradine, amoxycillin, piperacillin, imipenem, gentamicin, ciprofloxacin and trimethoprim was determined by an agar dilution method. Against species of Enterobacteriaceae not associated with producing an inducible cephalosporinase, cefpirome had a similar degree of activity to cefotaxime and was more active than ceftazidime and earlier cephalosporins. Against species with a high prevalence of inducible beta-lactamase production, cefpirome was superior to other cephalosporins; imipenem was also active against these isolates. Cefpirome was active against Pseudomonas aeruginosa, methicillin-sensitive staphylococci, non-enterococcal streptococci and Haemophilus spp. When the isolates were exposed to 0.1 mg/L of imipenem in agar plus the test agent, cefpirome had superior activity compared with the other cephalosporins tested for the Enterobacteriaceae, except Proteus vulgaris and Proteus penneri. 8.7% of Enterobacter spp., 7% of Citrobacter spp. and 6.7% of Morganella morganii had susceptibilities to beta-lactams suggesting constitutive hyperproduction of chromosomal cephalosporinase; cefpirome, unlike the other cephalosporins tested, was active against these isolates, although to a lesser degree than against the wild-type inducible isolates. No isolates were thought to produce an extended-spectrum beta-lactamase.

Cefpirome (HR 810), a New Cephalosporin

Using the standard agar dilution method we compared the in vitro activity of cefpirome (HR 810) with other broad spectrum antibiotics against clinical isolates of Enterobacteriaceae (478 strains), Pseudomonas aeruginosa (91), Xanthomonas maltophilia (27), Acinetobacter (36), Aeromonas hydrophila (28), Weeksella (1), staphylococci (361) and enterococci (50 strains). Against members of Enterobacteriaceae, Acinetobacter and A. hydrophila, cefpirome showed excellent activity with mean inhibitory concentrations required to inhibit 50% of strains (MIC50) ranging from < 0.03 to 2.0 mg/L, and MIC90 values ranging from 0.12 to 4.0 mg/L. 87% of P. aeruginosa isolates had an MIC of 4.0 to 16.0 mg/L. However, only 37% of X. maltophilia had an MIC of < 16.0 mg/L. All the 154 isolates of methicillin-susceptible Staphylococcus aureus were inhibited by cefpirome ⩽ 1.0 mg/L, whereas 53% of methicillin-resistant S. aureus had an MIC of ⩽ 16.0 mg/L. Of the 50 isolates of enterococci tested, 48 (96%) were inhibited by cefpirome ⩽ 16.0 mg/ L. Against Enterobacteriaceae the activity of cefpirome was superior to that of the other drugs tested, including ceftazidime, aminoglycosides and imipenem. The in vitro activity of cefpirome was superior or comparable to that of other antibiotic agents tested against methicillin-susceptible S. aureus, coagulase-negative staphylococci and enterococci.

In vitro activity of cefpirome compared with other third generation cephalosporins against nosocomial isolates in Argentina

The in vitro activity of cefpirome was evaluated against strains that showed conflicting results for third generation cephalosporins. Against isolates with derepressed inducible chromosomal cephalosporinase (n = 40) cefpirome was the sole cephalosporin with an MIC90 in the susceptible range; Klebsiella spp. with plasmid-mediated beta-lactamases (broad spectrum SHV-2 or SHV-2 type) (n = 40) remained most susceptible to ceftizoxime and cefpirome; against aminoglycoside-resistant Pseudomonas aeruginosa (n = 50), cefpirome was as active as ceftazidime and cefoperazone; against oxacillin-susceptible and oxacillin-resistant Staphylococcus spp., (n = 40), cefpirome was more active than other third generation cephalosporins but killing was inadequate against both oxacillin-resistant staphylococci and enterococci.

Inhibitory and Bactericidal Activity of Cefpirome and Cefotaxime against Blood Culture Isolates

Using a broth microtiter dilution method, minimum inhibitory (MIC) and minimum bactericidal concentrations (MBC) were determined for the aminothiazolyl cephalosporins cefpirome and cefotaxime against 436 blood culture isolates. At concentrations of less than or equal to 16 mg/l, cefpirome inhibited 82.3% of the isolates and cefotaxime 66.5%. At the same concentrations, cefpirome killed 60.0% of the isolates and cefotaxime 46.7%. Whereas the MIC values indicated a far better activity of cefpirome than cefotaxime against oxacillin-resistant Staphylococcus aureus, Enterococci and Pseudomonas aeruginosa, the MBC values showed a poor activity of both drugs against these strains. By comparison, cefpirome was the more active agent, covering a similar spectrum to that of cefotaxime with a slight additional activity against oxacillin-susceptible S. aureus and Staphylococcus epidermidis.

In vitro comparison of cefpirome and four other beta-lactam antibiotics alone and in combination with tobramycin against clinical isolates of Pseudomonas aeruginosa

In vitro susceptibility studies of cefpirome versus cefotaxime, ceftazidime, imipenem, and piperacillin alone and in combination with tobramycin were performed against 153 clinical isolates of Pseudomonas aeruginosa from four medical centers. The minimal inhibitory concentration (MIC) for each antibiotic alone was determined by a standardized dilution method. Antibiotic combination studies were performed using a modified checkerboard technique. Cefpirome alone was more active (MIC90 64 micrograms/ml) than piperacillin (MIC90 128 micrograms/ml) or cefotaxime (MIC90 256 micrograms/ml) but less active than imipenem (MIC90 2 micrograms/ml) or ceftazidime (MIC90 32 micrograms/ml). The addition of tobramycin reduced the MICs of all of the beta-lactam antibiotics except for imipenem. The MIC90 for cefpirome when combined with tobramycin was 8 micrograms/ml compared to 16 micrograms/ml for cefotaxime and piperacillin, 8 micrograms/ml for ceftazidime, and 4 micrograms/ml for imipenem. The combination of tobramycin and cefpirome proved to be additive or synergistic for 82% of the isolates (highest rate) compared to 31% with imipenem (lowest rate). The potent in vitro antipseudomonal activity of cefpirome alone and in combination with an aminoglycoside (tobramycin) suggests that this agent may play a useful role in the therapy of infections due to P. aeruginosa.

In-vitro and in-vivo activity of cefpirome (HR 810) against methicillin-susceptible and -resistant Staphylococcus aureus and Streptococcus faecalis

With cefpirome (HR 810) the MICs for both methicillin-resistant Staphylococcus aureus (MRSA) and for Streptococcus faecalis were 8.0 mg/l. At 4 x MIC, cefpirome killed MRSA as rapidly as did vancomycin while for enterococci, cefpirome, vancomycin or ampicillin alone were not bactericidal. However, all agents were bactericidal when combined with 2 mg/l of gentamicin, although gentamicin combined with cefpirome showed a smaller decrease in cfu/ml than the combination with ampicillin or vancomycin. A mouse thigh infection model was developed in which the thigh muscle was infected with bacteria and either no therapy or concurrent antibiotic therapy was initiated. On the subsequent day, the entire thigh muscle was quantitatively cultured. In this model, the numbers of enterococci at the infection site at 24 h were reduced by 2.1 logs with no treatment, 2.6 with cefpirome (25 mg/kg/day), 2.8 with ampicillin (150 mg/kg/day), and 2.7 with vancomycin (25 mg/kg/day). For MRSA the reductions were 1.1 logs with no therapy, 2.8 with vancomycin, and 3.0 with cefpirome. The apparent enhanced in-vivo activity of cefpirome for MRSA argues for further evaluation of this antibiotic for treatment of MRSA and other Gram-positive cocci, including enterococci.

Activity of cefpirome (HR810) against Pseudomonas aeruginosa strains with characterised resistance mechanisms to beta-lactam antibiotics.

The activities of cefpirome, cefotaxime, ceftazidime and ceftriaxone were compared against laboratory and clinical strains of Pseudomonas aeruginosa. Isolates with well characterised resistance mechanisms were included. Against carbenicillin-susceptible isolates cefpirome was more active than cefotaxime and ceftriaxone, but less active than ceftazidime. The activity of all four cephalosporins was impaired against isolates that had increased intrinsic (i.e. non-beta-lactamase-mediated) carbenicillin resistance. However, cefpirome and ceftazidime, unlike the other compounds, remained active at less than 16 mg/l against such strains, whereas cefotaxime and ceftriaxone largely failed to do so. Cefpirome maintained full activity against most isolates with plasmid-mediated beta-lactamases, as did the other cephalosporins. Transconjugant studies indicated that only LCR-1 and PSE-2 enzymes could protect P. aeruginosa against cefpirome. Isolates with partial or total chromosomal beta-lactamase derepression were highly resistant to cefotaxime and ceftriaxone (MIC greater than 128 mg/l) but only those with total derepression were resistant (MIC 16-32 mg/l) to cefpirome and ceftazidime, while those with partial derepression were sensitive to 4-8 mg/l of the latter antibiotics. Comparison of cefpirome MICs for totally-derepressed P. aeruginosa and their enzyme-deficient mutants indicated that chromosomal beta-lactamase gave less protection against cefpirome than against other cephalosporins tested. Cefpirome was a weak inducer of class I beta-lactamases. Overall, therefore, cefpirome behaved similarly to ceftazidime against the different P. aeruginosa resistance types.

In vitro antimicrobial activity of cefpirome, a new cephalosporin with a broad antimicrobial spectrum.

The in vitro activity of cefpirome (HR 810), a new cephalosporin antibiotic having a 2,3-cyclopentenopyridine group in the 3-position side chain, was compared with in vitro activities of 5 other cephalosporins. HR 810 showed a broad spectrum of antimicrobial activity against Gram-positive and Gram-negative bacteria when tested using 71 standard strains and 876 clinical isolates. HR 810 inhibited 70% of the clinically isolated Staphylococcus aureus and Staphylococcus epidermidis strains when used at 0.59-0.84 microgram/ml, 2- to 25-fold lower than values of reference antibiotics, and the compound was also highly effective against Enterococcus faecalis which is relatively resistant to most of the existing cephem antibiotics. The activity of HR 810 against Enterobacteriaceae members (11 species), based on its minimal inhibitory concentrations inhibiting 90% of bacterial growth (MIC90S), was the highest among the cephalosporins used. Especially against Enterobacter species and Citrobacter freundii, the MIC90S of the compound were 4- to 64-fold lower than the values of the other antibiotics. Against Pseudomonas aeruginosa, HR 810 was as active as cefoperazone, an antipseudomonal agent. The minimal bactericidal concentrations (MBCs) of HR 810 were equal to or only 2-fold greater than the MICs for most of 12 standard strains tested. The compound markedly decreased viable bacterial counts at its MICs, thus showing strong bactericidal activities. The in vitro activity of HR 810 was not affected by pH or human serum content of agar media, but the activity against Gram-negative bacteria was lowered as the inoculum size increased.

Comparative in vitro activity of cefpirome (HR 810) against gram-positive isolates from cancer patients

The activity of cefpirome against gram-positive isolates from cancer patients was compared to that of currently available extended-spectrum cephalosporins. Cefpirome was active against methicillin-susceptible, coagulase-positive, and coagulase-negative staphylococci. It was the most active agent against streptococci belonging to Lancefield groups A, B and G and Streptococcus pneumoniae. 76% of enterococcal isolates were susceptible to cefpirome - far more than any of the other agents tested.