Comparative antibacterial activity of a new monobactam, carumonam (RO 17-2301, AMA 1080) on hospital bacteria resistant to beta lactams

In vitro activity of a new monobactam, carumonam (RO 17-2301, AMA 1080) was tested against 370 hospital bacterial isolates. Results were compared to aztreonam, cefotaxime, cefmenoxime, latamoxef, ceftazidime, ceftriaxone, pefloxacin against Enterobacteriaceae, to aztreonam, piperacillin, cefoperazone, cefsulodin, ceftazidime, imipenem and pefloxacin against P. aeruginosa. All Enterobacteriaceae strains produced cephalosporinases and all P. aeruginosa strains were ticarcillin resistant. MIC 90% of carumonam against Enterobacteriaceae strains was lower than 0.25 mg/l for P. mirabilis, P. vulgaris, P. stuartii, Salmonella sp., ranged from 0.25 to 0.5 mg/l for Klebsiella sp. and S. marcescens, from 1 to 2 mg/l for E. coli and P. morganii, and from 4 to 8 mg/l for C. freundii and E. cloacae. The rate of strains inhibited with 4 mg/l of carumonam was 95.3%. So carumonam was at the second place from eight tested products, after latamoxef (97.5% of susceptible strains). Carumonam was active against second generation cephalosporins resistant strains when these strains were susceptible or intermediate to cefotaxime. Strains resistant to this compound escaped to its action. Its activity against A. calcoaceticus was weak (22.6% of strains inhibited by 4 mg/l), but was superior to that of cefsulodin against ticarcillin resistant P. aeruginosa strains (54.5 versus 16.1% of susceptible strains). However carumonam was less active against this last species than ceftazidime or imipenem (92.6 and 91% of susceptible strains respectively).     

Antimicrobial resistance patterns among aerobic Gram-negative bacilli isolated from patients in intensive care units: results of a multicenter study in Russia

Objective: To determine the antimicrobial resistance patterns among aerobic Gram-negative bacilli isolated from patients in intensive care units (ICUs) in different parts of Russia.
Methods: During 1995–96, 10 Russian hospitals from different geographic areas were asked to submit 100 consecutive Gram-negative isolates from patients with ICU-acquired infections. Minimal inhibitory concentrations (MICs) of 12 antimicrobials were determined by Etest and results were interpreted according to National Committee for Clinical Laboratory Standards (NCCLS) guidelines.
Results: In total, 1005 non-duplicate strains were obtained from 863 patients. The most common species were Pseudomonas aeruginosa (28.8%), Escherichia coli (21.4%), Klebsiella pneumoniae (16.7%), Proteus mirabilis (9.7%), Enterobacter spp. (8.2%) and Acinetobacter spp. (7.7%). High levels of resistance were seen to second- and third-generation cephalosporins, ureidopenicillins, β-lactam/β-lactamase inhibitor combinations and gentamicin. The most active agents were imipenem (no resistance in Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterobacter spp. and Acinetobacter spp., 7% resistance in Pseudomonas aeruginosa ), amikacin (7% resistance in Pseudomonas aeruginosa and Acinetobacter spp., 4% in Enterobacter spp., 1% in Escherichia coli and Proteus mirabilis, no resistance in Klebsiella pneumoniae ) and ciprofloxacin (15% resistance in Pseudomonas aeruginosa, 5% in Enterobacter spp. and Proteus mirabilis, 2% in Klebsiella pneumoniae, 1% in Escherichia coli ).
Conclusions: Second- and third-generation cephalosporins, ureidopenicillins, β-lactam/β-lactamase inhibitor combinations and gentamicin cannot be considered as reliable drugs for empirical monotherapy for aerobic Gram-negative infections in ICUs in Russia.     

Frequency of germ isolation from urinary infections in community practice; their sensitivity to 7 antibiotics including a combination of amoxicillin and clavulanic acid. Evaluation on 1611 samples

A multicenter study including 10 outpatient private laboratories (hospital laboratories excluded) was carried out in France. 1,611 urines samples from patients with UTI were collected during the forth trimester of 1987. The most frequently recovered pathogens were: E. coli (71%), Proteus mirabilis (9%), Staphylococcus coagulase (6%), Klebsiella (6%), Enterobacter (2%). Other sorts (Streptococcus D, Proteus sp, Pseudomonas aeruginosa, Enterobacter sp) were infrequent (less than 1%). The sensitivity of the aerobic Gram-negative bacteria to ampicillin, clavulanic acid-amoxicillin, cephalothin, gentamicin, pipemidic acid, norfloxacin and co-trimoxazole was tested.     

In vitro activity of cefmenoxime (SCE 1365) against 616 hospital strains of gram-negative bacilli chosen for beta-lactam resistance. Comparison with cefotaxime, lamoxactam and ceftazidime

The in vitro activity of a new cephalosporin, cefmenoxime, was tested by an agar dilution procedure against 616 strains of Gram negative rods resistant to various beta-lactams and was compared with that of cefotaxime, lamoxactam, ceftazidime (and cefsulodin against P. aeruginosa). A high activity was demonstrated on many species of tested Enterobacteriaceae including E. coli, K. pneumoniae, S. marcescens, E. cloacae resistant to the first generation cephalosporins, Proteus sp., Providencia and C. freundii, with MIC geometric mean values from 0,028 to 0,33 microgram by ml. These values were nearly similar to those given by cefotaxime or lamoxactam and inferior to those given by ceftazidime. Cefmenoxime however showed a low activity (MIC geometric means from 19,5 to 25,5 micrograms by ml) against E. cloacae resistant to second generation cephalosporins (the better agent was lamoxactam), A. calcoaceticus (the better agent was ceftazidime) and carbenicillin-resistant P. aeruginosa (here ceftazidime and cefsulodin gave better performances).     

In vitro activity of N-formimidoyl-thienamycin in comparison to that of moxalactam and cefotaxime against gentamicin-resistant gram-negative bacteria

The inhibitory and bactericidal activity of N-formimidoyl-thienamycin in vitro against 131 clinical isolates selected for their gentamicin resistance was compared with that of cefotaxime and moxalactam. All strains were inhibited by N-formimidoyl-thienamycin concentrations within a range of 0.12–4 mg/l. N-formimidoyl-thienamycin was less active than cefotaxime and moxalactam againstEscherichia coli andKlebsiella spp., and more active than all other antibiotics tested againstSerratia spp.,Enterobacter cloacae, Pseudomonas aeruginosa andAcinetobacter spp. In contrast to the other antibiotics N-formimidoyl-thienamycin showed a narrow margin of difference between minimal inhibitory and minimal bactericidal concentrations. N-formimidoyl-thienamycin is a promising antibiotic for the treatment of hospital infections with multi-resistant organisms.     

In vitro antimicrobial activity of diethyldithiocarbamate and dimethyldithiocarbamate against methicillin-resistant Staphylococcus

Staphylococcus aureus has appeared which is highly resistant to both methicillin and aminoglycosides. Current therapy involves long-term intravenous therapy of vancomycin. Since vancomycin is currently the only drug used to treat these patients, there is a need to develop additional antimicrobial therapy. The in vitro antimicrobial effect of the metal chelator, diethyldithiocarbamate (DDTC) and its structural analog dimethyldithiocarbamate (DMTC) were investigated. Both DDTC and DMTC were effective against S. aureus including methicillin-resistant S. aureus (MRSA). By agar diffusion, DDTC at 10 micrograms per disk produced zone sizes of 12 to 21 mm and at 100 micrograms per disk produced zone sizes of 26 to 34 mm against MRSA. The DMTC produced slightly greater zone sizes against MRSA of 16 to 24 mm and 24 to 37 mm for 10 micrograms per disk and 100 micrograms per disk, respectively. The minimum inhibitory concentration (MIC) for DMTC against MRSA was 6 micrograms per ml. Both DDTC and DMTC were also effective against enterococci, Proteus mirabilis, Klebsiella pneumoniae, Klebsiella oxytoca, Escherichia coli, Enterobacter cloacae, Enterobacter aerogenes, Salmonella species, Serratia marcescens and Citrobacter freundii at 100 micrograms per disk. The MICs of DMTC for Klebsiella pneumoniae, Klebsiella oxytoca, Escherichia coli, Salmonella and Citrobacter freundii were approximately 128 micrograms per ml while the MICs for Proteus vulgaris, Proteus mirabilis, Pseudomonas aeruginosa and Serratia marcescens was greater than or equal to 256 micrograms per ml. In addition, DMTC was synergistic with gentamicin against MRSA and coagulase-negative staphylococcus species, Enterobacter cloacae, Klebsiella pneumoniae and Pseudomonas aeruginosa. Additive and synergistic effects of DMTC were displayed with gentamicin against S. aureus including methicillin-resistant S. aureus.(ABSTRACT TRUNCATED AT 250 WORDS)     

Drug sensitivity patterns of bacterial isolates from septic post-operative wounds in a regional referral hospital in Uganda

Background: Wound infections have been a problem in the field of surgery for a long time. Advances in control of infections have not completely eradicated this problem because of development of drug resistance. Antimicrobial resistance can increase complications and costs associated with procedures and treatment. Objective: A study was carried out on drug sensitivity patterns of bacterial isolates from septic postoperative wounds in Jinja hospital, Uganda. This study was designed to determine the distribution of bacterial pathogens isolated from septic post-operative wounds and their antimicrobial susceptibility patterns. Method: Specimens of pus swabs were collected aseptically and analysed in the laboratory. Colony characteristics and Grams technique were used to differentiate the organisms. Biochemical tests were done to confirm the species of the organisms. Sensitivity testing was done on the isolates using the disk diffusion method. Results: Pathogenic bacteria were recovered from 58.5% of the specimens. The isolates were: S.aureus (45.1%), Coliforms (16.9%), Proteus mirabilis (11.3%), P.aeruginosa (9.9%), Klebsiella pneumoniae (7.0%) and Enterobacter spp (2.82%). Most of the organisms were sensitive to gentamicin, ciprofloxacin and ceftazidime. There was resistance to ampicillin, amoxycillin and chloramphenicol. Staphylococcus aureus was generally sensitive to gentamicin (87.5%), ciprofloxacin (68.7%) and methicillin (75%), but resistant to erythromycin (56.2%) and ampicillin (97%). Most of the gram-negative bacteria isolated (Coliforms, P.aeruginosa, E.coli, Proteus mirabilis, and Klebsiella pneumoniae) were sensitive to Ciprofloxacin, Gentamicin and Ceftazidime but resistant to Ampicillin, Amoxycillin and Chloramphenicol. Methicillin-resistant Staphylococcus aureus (MRSA) strains formed 25% of this species. Pseudomonas aeruginosa was sensitive to gentamicin (87.5%) and ceftazidime (85.7%) but showed resistance to ciprofloxacin (57.2%). Some organisms e.g. S.aureus, Pseudomonas aeruginosa and Proteus mirabilis exhibited multi-drug resistance to the antibiotics tested. Conclusion: Since a high proportion of samples had positive cultures, infection control is recommended as a strategy to minimise spread of resistant organisms. It is recommended that gentamicin, ciprofloxacin and ceftazidime be used in preference to ampicillin and amoxycillin for treatment of septic wounds. There is need to develop national surveillance of antibiotic- resistant organisms.     

Serum bactericidal activity after administration of four cephalosporins in healthy volunteers

Serum bactericidal activity (SBA) was determined against ten strains each ofStaphylococcus aureus, Klebsiella pneumoniae, Proteus vulgaris andEnterobacter cloacae in six volunteers 1 h and 4 h after intravenous infusion of 1 g and 2 g cefotaxime and cefmenoxime, and 2 g flomoxef, and against ten strains ofPseudomonas aeruginosa after infusion of 1 g and 2 g ceftazidime. Flomoxef showed the highest SBA against methicillin-susceptibleStaphylococcus aureus. All cephalosporins had high SBA against gram-negative rods. Cefotaxime had the highest SBA againstKlebsiella pneumoniae andEnterobacter cloacae. The SBA againstPseudomonas aeruginosa after 1 g and 2 g doses of ceftazidime was very similar.     

In vitro bacteriostatic activity of cefmenoxime (SCE 1365), cefotaxime and moxalactam

The in vitro activity of cefmenoxime (SCE 1365), a new cephalosporin derivate was compared with two other "third generation" cephalosporins: cefotaxime and moxalactam. Cefmenoxime as cefotaxime and moxalactam were very active against 305 cephalosporinase-producing and cephalosporinase-non-producing Enterobacteriaceae. Cefmenoxime was the most active against Serratia marcescens, Citrobacter freundii, Morganella morganii, Salmonella, Shigella and Yersinia enterocolitica with a mean MIC at least twice lower. Several strains of the species Hafnia alvei, Providencia stuartii and Proteus vulgaris were more resistant. Against Haemophilus influenzae, the activity of the three cephalosporins was higher with a mean MIC between 0,030 and 0,040 microgram/ml. Against carbenicillin-sensible or carpenicillin-resistant Pseudomonas aeruginosa or Acinetobacter calcoaceticus, the three cephalosporins were not performant. Against Staphylococcus aureus, cefmenoxime and cefotaxime had an identical activity with a mean MIC of 1,5 microgram/ml against methicillin-sensible strains and a mean MIC of 5,5 micrograms/ml against methicillin-resistant strains.     

Resistance rates to commonly used antimicrobials among pathogens of both bacteremic and non-bacteremic community-acquired urinary tract infection.

This study examined the distribution of organisms and their antimicrobial resistance in patients admitted due to acute bacteremic and non-bacteremic community-acquired urinary tract infection (UTI). During a period of 1 year and 1 month, a total of 201 patients and 253 bacterial isolates were studied. Fever higher than 38.5 degrees C was significantly more common in the bacteremic group than the non-bacteremic group (68% vs 48%; p<0.05). Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Proteus mirabilis were the most common organisms isolated. E. coli was the leading pathogen and it was significantly more predominant in bacteremic UTI than non-bacteremic UTI (73% vs 49%; p<0.01). Bacteria other than E. coli (i.e., K. pneumoniae, P. aeruginosa, Proteus spp., Morganella morganii, Enterobacter cloacae, Citrobacter spp., Acinetobacter baumannii, Serratia marcescens, and Providencia spp.) were more common in non-bacteremic UTI than bacteremic UTI (44% vs 22%; p<0.01). E. coli isolated from both bacteremic and non-bacteremic patients had a high rate of resistance to ampicillin (80%), cephalothin (59%), gentamicin (29%), piperacillin (61%), trimethoprim-sulfamethoxazole (56%), amoxicillin-clavulanic acid (34%), and ticarcillin-clavulanic acid (36%). Isolates of P. aeruginosa, K. pneumoniae, and Proteus spp. from the non-bacteremic group showed a higher proportion of resistance to extended-spectrum cephalosporins, aminoglycosides (netilmicin and amikacin) and ciprofloxacin. The emergence of a high rate of resistance to commonly used antimicrobials (ampicillin, cephalothin, gentamicin, trimethoprim-sulfamethoxazole, piperacillin, amoxicillin-clavulanic acid and ticarcillin-clavulanic acid) may have an impact on the antibiotic treatment of patients admitted due to acute community-acquired bacteremic or non-bacteremic UTI in Taiwan. Further studies are needed to clarify the impact of antimicrobial resistance on the outcome in these conditions.     

Value of moxalactam in the treatment of meningitis: efficacy and meningeal diffusion

15 bacterial meningitis (Haemophilus: 7, Meningococci: 3, Proteus: 1, Enterobacter: 2, E. coli: 1 and Klebsiella: 1) are treated with moxalactam. The diffusion of moxalactam into the cerebrospinal fluid is good and regular. Excellent clinical results are obtained.     

Comparative study of ceftriaxone, cefotaxime and moxalactam against 150 Gram negative strains (author's transl)

The in vitro activity of ceftriaxone, a new cephalosporine derivative was compared with two other "third generation" cephalosporins, cefotaxime and moxalactam. 150 strains of Gram negative bacilli were used in this study. Ceftriaxone as cefotaxime and moxalactam were very active against most of the 104 multiresistant Enterobacteriaceae. Ceftriaxone was the most active against Proteus providencia with a mean MIC of 0.007 microgram/ml. Cefotaxime and ceftriaxone were less active than moxalactam against Enterobacter with MIC higher or equal to 32 micrograms/ml. The three cephalosporins had an almost identical activity against carbenicillin resistant Pseudomonas with an MIC higher than 4 micrograms/ml. MIC against Acinetobacter were higher or equal to 16 micrograms/ml. Moxalactam was the most active against Bacteroides fragilis with a mean MIC of 0.5 micrograms/ml; ceftriaxone and cefotaxime had a mean MIC of 2 to 4 micrograms/ml.     

Gram-negative bacilli in burns

In a period of two years, 865 strains of Gram-negative bacilli other than Pseudomonas aeruginosa isolated from burns were identified by a range of tests. The commonest species were Proteus mirabilis, Escherichia coli, and Enterobacter cloacae. Many strains of Klebsiella aerogenes, Enterobacter aerogenes, and Bacterium anitratum were also found.A large proportion of the strains were tested for sensitivity to nalidixic acid, ampicillin, kanamycin, chloramphenicol, tetracycline, and carbenicillin, and smaller numbers of strains were tested for sensitivity to cephaloridine, polymyxin, streptomycin, sulphadiazine, sulfamylon, and trimethoprim. The proportion of strains sensitive and resistant to different antibacterial agents varied widely with species of bacteria. A large proportion of the strains of E. coli and P. mirabilis were resistant to ampicillin, which was much used in treatment; resistance appeared least often towards nalidixic acid, kanamycin, trimethoprim, and gentamicin. Multiple resistance occurred less often among strains of E. coli than among Klebsiella spp, Enterobacter spp, and P. mirabilis.Phage and serological typing of Ps. aeruginosa showed that most infections of burns with this organism were due to strains previously found in other patients in the same ward. Taken with other evidence, this supported the view that most infections with Ps. aeruginosa were not acquired from the patient's own flora but from sources in the hospital environment.     

Concentration-dependency of beta-lactam-induced filament formation in Gram-negative bacteria.

Ceftazidime and cefotaxime are beta-lactam antibiotics with dose-related affinities for penicillin-binding protein (PBP)-3 and PBP-1. At low concentrations, these antibiotics inhibit PBP-3, leading to filament formation. Filaments are long strands of non-dividing bacteria that contain enhanced quantities of endotoxin molecules. Higher concentrations of ceftazidime or cefotaxime cause inhibition of PBP-1, resulting in rapid bacterial lysis, which is associated with low endotoxin release. In the present study, 37 isolates of Escherichia coli, Klebsiella spp., Pseudomonas aeruginosa and Acinetobacter spp. were studied over a 4-h incubation period in the presence of eight concentrations of ceftazidime or cefotaxime. As resistance of Gram-negative bacteria is an emerging problem in clinical practice, 14 isolates of E. coli and Klebsiella pneumoniae that produced extended-spectrum beta-lactamases (ESBLs) were also investigated. Morphological changes after exposure to the beta-lactam antibiotics revealed recognisable patterns in various bacterial families, genera and isolates. In general, all isolates of Enterobacteriaceae produced filaments within a relatively small concentration range, with similar patterns for E. coli and K. pneumoniae. Pseudomonas and Acinetobacter spp. produced filaments in the presence of clinically-relevant concentrations of both antibiotics as high as 50 mg/L. In all genera, filament-producing capacity was clearly related to the MIC. Ceftazidime induced filament production in more isolates and over wider concentration ranges than did cefotaxime. Interestingly, ESBL-producing isolates were not protected against filament induction. The induction of filament production may lead to additional risks during empirical treatment of severe infections.     

High frequency of antibiotic resistance among Gram-negative isolates in intensive care units at 10 Swedish hospitals

Objective: To investigate the resistance rates among Gram-negative isolates in Swedish intensive care units (ICUs).
Method: During 1994–95, members of the Swedish Study Group collected, on clinical indication, 502 consecutive initial isolates of Gram-negative bacteria from patients admitted to ICUs at 10 Swedish hospitals and performed minimal inhibitory concentration (MIC) determinations with the Etest. Breakpoints were defined according to the criteria of the Swedish Reference Group for Antibiotics (SRGA).
Results: The distribution of bacterial species was: Escherichia coli > Klebsiella spp. > Enterobacter spp. > Pseudomonas aeruginosa > Haemophilus spp. > Proteus spp. > Stenotrophomonas maltophilia > Citrobacter spp. > Acinetobacter > Pseudomonas. spp. > Morganella morganii > Serratia spp. Together these constituted 97% of all isolates. The frequencies of resistance for all the initial Gram-negative isolates were: ceftazidime 6.8%, cefotaxime 14.9%, ceftriaxone 18.5%, cefuroxime 44.1%, ciprofloxacin 4.2%, co-trimoxazole 17.8%, gentamicin 5.8%, imipenem 8.6%, piperacillin 20.2%, piperacillin/tazobactam 12.9% and tobramycin 5.8%.
Conclusions: Among Gram-negative isolates in Swedish ICUs, a very high frequency of resistance was seen to cefuroxime, and rather high frequencies of resistance to cefotaxime, ceftriaxone, piperacillin and piperacillin/tazobactam. These drugs cannot be recommended for further use as empirical monotherapy for severe ICU-acquired Gram-negative infections in ICUs in Sweden.     

Activity of the amoxicillin-clavulanic acid (augmentin) combination on strains of hospital isolates

All strains of Staphylococcus aureus and Gram negative bacilli (Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter) isolated from 01.01 to 03.31.83 were studied using agar diffusion with augmentin-impregnated discs (amoxicillin 20 micrograms + clavulanic acid 10 micrograms). Augmentin is active against penicillinase-producing Staphylococci susceptible to methicillin, whereas methicillin-resistant strains are also resistant to augmentin. According to the susceptibility of strains to amoxicillin, carbenicillin and cefalotin, Enterobacteriaceae can be divided into five main phenotypes, of which four are resistant. "RSR" and "RRR" phenotypes, which are cephalosporinase producers, are chiefly found among Enterobacter, Serratia, Citrobacter and indole + Proteus; in these groups a change in inhibition diameters indicating activity of augmentin is observed only in a significant number of Proteus vulgaris strains. "RRS" and "RRI" strains are penicillinase producers found mainly among E. coli, Klebsiella pneumoniae and oxytoca, and Proteus mirabilis; they emerge as very susceptible to augmentin. Pseudomonas aeruginosa is never susceptible to augmentin. Augmentin is slightly more active than amoxicillin on some Acinetobacter strains but the difference is too inconsiderable to be of clinical significance.     

Antibacterial activity of the new carbapenem meropenem (SM-7338) against clinical isolates

The in vitro antibacterial activity of the new carbapenem antibiotic meropenem (SM-7338) against 567 clinical isolates was evaluated. SM-7338 exhibited activity against a broad spectrum of organisms, including aerobes and anaerobes, and was superior to the other beta-lactam drugs tested (piperacillin, cefotaxime, ceftazidime, ceftriaxone, cefoxitin). SM-7338 was more active than imipenem, gentamicin and amikacin againstEnterobacter cloacae andPseudomonas aeruginosa. SM-7338 was less potent than imipenem against staphylococci and enterococci, but the activity of the two antibiotics against anaerobes was similar. SM-7338 and imipenem showed a high bactericidal activity at a concentration of 2–4 x MIC.     

Pharmacokinetic and microbial susceptibility studies of ceftriaxone

The in vitro activity of ceftriaxone, a new parenteral cephalosporin, was tested against 450 strains isolated from blood cultures and compared with that of various other antibiotics. The compound was comparable to cefotaxime for all species tested. Its was more potent than cefoperazone, cefamandole and ticarcillin in inhibitingEnterobacteriaceae (Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, indole-positiveProteus spp. andSerratia marcescens). The MIC₉₅ of ceftriaxone for these strains was 0.5Μg/ml. The drug was less active againstStaphylococcus aureus than cefamandole, cloxacillin and vancomycin, but most isolates were inhibited by 4Μg/ml. AgainstPseudomonas aeruginosa, ceftriaxone was comparable in activity to ticarcillin (MIC₉₅=64Μg/ml), and inferior to cefoperazone, ceftazidime and cefsulodine. Levels of ceftriaxone in serum and various body fluids were determined by bio-assays. Due to its very long half-life (8 h), ceftriaxone serum levels 24 h after i.v. or i.m. injection of 1 and 2 g were still above the MIC₉₅ of all strains tested exceptPseudomonas aeruginosa. Levels in bile, synovial and cerebro-spinal fluids were high.     

Clinical consequences of development of resistance to third generation cephalosporins

Eighteen patients are described in whom initially sensitive microorganisms were replaced by resistant isolates during administration of ceftriaxone (n=8), cefoperazone (n=5), moxalactam (n=4), cefotaxime (n=2) or ceftazidime (n=1), despite combination with aminoglycosides. All patients had documented gram-negative infections; in 12 patients underlying haemaotological diseases were present. Resistant strains ofEnterobacter cloacae (14),Serratia marcescens (4),Klebsiella oxytoca (3),Pseudomonas aeruginosa (2) andCitrobacter freundii (2) emerged within 2 to 19 (mean 9) days after the beginning of treatment. In 12 patients relapse or secondary infections occurred. Seven of the patients with haematological disorders died. Resistance development was seen in 8 of 29 patients on ceftriaxone and 4 of 10 patients on moxalactam during prospective evaluations; the other drugs were used sporadically. Thus, selection of resistant bacteria is relatively frequent and may have serious clinical consequences in patients with impaired host-defense mechanisms.     

Pseudomonas aeruginosa: acquired in vitro resistance to beta-lactams

The development of resistance acquired in vitro to 5 semi-synthetic penicillins: carbenicillin, ticarcillin, azlocillin, mezlocillin, piperacillin and to 5 cephalosporins: cefotaxime, cefoperazone, moxalactam, cefsulodin and ceftazidime, was compared in 6 strains of Pseudomonas aeruginosa. The strains were selected on the basis of their phenotypic resistance: 3 were susceptible to all the betalactam antibiotics tested, 1 was resistant to carbenicillin and ticarcillin but remained susceptible to the others, 2 were susceptible to cefsulodin and ceftazidime but resistant to the others. The development of resistance was investigated by subsequent passages in liquid medium: up to 15 passages or up to an MIC of 4 096 mg/l for a penicillin or 512 mg/l for the cephalosporins. Irrespectively of the phenotypic resistance, for all cephalosorins the MIC became greater than or equal to 64 mg/l and very often greater than or equal to 512 mg/l after 1 to 3 passages. For the penicillin susceptible strains very high MICs were obtained more rapidly with azlocillin and piperacillin (1-2 passages) than with carbenicillin or ticarcillin (5-9 passages). These results are not in favour of a monotherapy with betalactam antibiotics, especially cephalosporins, in the treatment of Pseudomonas aeruginosa infections, but suggest the preferential use of carbenicillin and especially ticarcillin for sensitive isolates.