In Vitro Interactions of Aminoglycosides with Imipenem or Ciprofloxacin against Aminoglycoside Resistant Acinetobacter baumannii

Summary

The in vitro interactions between gentamicin, tobramycin, netilmicin and amikacin with imipenem and ciprofloxacin were evaluated by the killing curve technique against 20 clinical isolates of Acinetobacter baumannii highly resistant to aminoglycosides which were susceptible or moderately susceptible to imipenem and resistant or moderately susceptible to ciprofloxacin. Imipenem enhanced killing by gentamicin, tobramycin, netilmicin and amikacin in tests with 9, 12, 10 and 15 strains (45-75%) while ciprofloxacin with 3, 7, 5 and 6 strains (15-35%) respectively. Interaction results were influenced by the height of aminoglycoside minimum bactericidal concentrations (MBCs) but were independent of imipenem or ciprofloxacin MBCs and the presence of aminoglycoside modifying enzymes. It is concluded that enhanced killing after aminoglycoside interaction with imipenem or ciprofloxacin versus A. baumannii cannot be predicted but it should be carefully tested in vitro. The in vivo significance of the reported findings mandates clinical studies in humans.     

In- Vitro Susceptibility of Clinical Isolates of Pseudomonas aeruginosa to β-Lactam and Aminoglycoside Antibiotics

Summary

The in-vitro susceptibilities of 198 isolates of Pseudomonas aeruginosa from clinical human specimens were determined by an agar dilution technique against (β-lactams and aminoglycosides. These isolates were susceptible to imipenem, aztreonam and ceftazidime with the minimum inhibitory concentration (MIC) for 90% of the strains tested being 8, 16 and 8 μg/ml, respectively. Aminoglycosides, except amikacin, had low activity (MIC90 > 128 μg/ml).     

Comparative antimicrobial potency of meropenem tested against Gram-negative bacilli: report from the MYSTIC surveillance program in the United States (2004)

The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program is a longitudinal resistance surveillance network of more than 100 medical centers worldwide monitoring the susceptibility of bacterial pathogens to carbapenems and other broad-spectrum agents. In 2004 (year six), the antimicrobial activity of 12 broad-spectrum agents was assessed against 2,799 Gram-negative bacterial isolates submitted from 15 United States (USA) medical centers using Clinical and Laboratory Standards Institute (CLSI; formerly NCCLS) recommended methods. Meropenem continued to demonstrate a high potency with MIC90 values 4- to 32-fold lower than imipenem against the Enterobacteriaceae. The wide spectrum of activity for meropenem against all Gram-negative isolates was demonstrated by the overall rank order of percentage susceptibility at CLSI breakpoints: amikacin (96.5%) > meropenem (96.0%) > imipenem (95.8%) > piperacillin/tazobactam (91.5%) > tobramycin (91.4%) > cefepime (91.2%) > ceftazidime (89.0%) > gentamicin (88.0%) > aztreonam (81.5%) > levofloxacin (80.5%) > ciprofloxacin (80.2%) > ceftriaxone (69.1%). Only the aminoglycosides (84.5%) and carbapenems (76.1-83.8%) exhibited acceptable levels of susceptibility against the Acinetobacter spp. isolates as this species group became more resistant to all antimicrobial classes. A continued increase in the resistance rate for both ciprofloxacin and levofloxacin over the six years was observed, most alarming among Escherichia coli (20.2-20.7%) and indole-positive Proteus species (34.4-42.2%) isolates, some documented as clonal. Continued surveillance of these broad-spectrum antimicrobial agents appears warranted to monitor the potency and spectrum of activity against Gram-negative pathogens causing serious infections and the emergence of new or novel resistance mechanisms that could compromise carbapenem therapy.     

In- Vitro Activity of Meropenem,a New Carbapenem,Against Imipenem-Resistant Pseudomonas aeruginosa and Xanthomonas maltophilia

Summary

The activity of meropenem, a new carbapenem, as well as imipenem, ceftazidime, aztreonam, tobramycin, amikacin and ciprofloxacin against 18 strains of Xanthomonas maltophilia and 23 strains of Pseudotnonas aeruginosa resistant to imipenem was tested. All strains of X. maltophilia were resistant to both penems. Ceftazidime, tobramycin and ciprofloxacin were the most active antimicrobial agents against this specie. 17% of imipenem-resistant strains of P. aeruginosa were sensitive to meropenem. Ciprofloxacin, amikacin and aztreonam were the most effective agents against these strains.     

In Vitro Activity of Meropenem against Ciprofloxacin-Resistant Enterobacteriaceae and Pseudomonas aeruginosa

Abstract

The in-vitro susceptibilities of a total of 174 ciprofloxacin-resistant Enterobacteriaceae and Pseudomonas aeruginosa were determined. According to the BSAC and NCCLS breakpoints, meropenem, aztreonam, ceftibuten, ceftazidime, imipenem and cefotaxime were the most active (>90%) antimicrobial agents tested against Enterobacteriaceae. Susceptibility of these strains to piperacillin/tazobactam, cefpodoxime and cefixime (84.96%) was higher than that to tobramycin, gentamicin and fosfomycin (50-75%). More than 90% of P. aeruginosa were susceptible to meropenem when both interpretative susceptibility breakpoint criteria were used. Piperacillin, piperacillin/tazobactam and ceftazidime were active against 50-75% of the same strains. Meropenem was the most active antimicrobial tested against all ciprofloxacin-resistant clinical isolates assayed.     

Susceptibility of Bacterial Isolates From Turkey - A Report From the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program

Abstract

The study monitored the susceptibility of nosocomial pathogens to meropenem and comparator antimicrobial agents isolated as part of the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program from Turkish university hospitals. In terms of minimum inhibitory concentration 90% (MIC₉₀) values, meropenem was two- and eight-fold more active than imipenem against Escherichia coli and Klebsiella pneumoniae, respectively. 40.5% of K. pneumoniae, 23.1% of Klebsiella oxytoca and 15.3% of E. coli isolates were extended-spectrum β-lactamase (ESBL) producers. Piperacillin/tazobactam was the most active agent against isolates of Pseudomonas aeruginosa, followed by meropenem and imipenem. Against Acinetobacter baumannii isolates, meropenem and imipenem were the most active agents. Continued surveillance by the MYSTIC Program appears to be prudent to help focus on effective empiric treatment regimens.     

Antibiotic Resistance Among Gram-Negative Non-Fermentative Bacteria at a Teaching Hospital in Saudi Arabia

Abstract

The incidence and antimicrobial resistance of Gram-negative non-fermentative bacteria isolated over 1 year at King Abdulaziz University Hospital, Jeddah, Saudi Arabia were investigated. A total of 499 of these microorganisms were collected and account for 16% of all Gram-negative bacteria isolated. The most common species were Pseudomonas aeruginosa 291 (56%), Acinetobacter baumannii 170 (34%), and Stenotrophomonas maltophilia 35 (7%). 168 (34%) of these microorganisms were isolated from Intensive Care Unit (ICU), 147 (30%) from General Medicine, and 24 (25%) from Surgery wards. ICU was the main site of isolation of P. aeruginosa and S. maltophilia, while A. baumannii was more frequently isolated from medicine and surgery units. The vast majority of the isolates were resistant to many antibiotics tested. The antimicrobial resistance patterns of P. aeruginosa showed lowest resistance to imipenem (13%), amikacin (17%), and ciprofloxacin (18%). Imipenem was also the most active antimicrobial agent against A. baumannii (15%) resistance. S. maltophilia exhibited multi-drug resistance, and was susceptible only to sulfonamide (6%).     

Epidemiology of Antibiotic Resistance in Human Isolates of Enterobacteriaceae in Sicily

Summary

The Authors have studied the antimicrobial susceptibility of 1073 clinical isolates of various genera of Enterobacteriaceae (collected during the period July-December 1988) to ampicillin, piperacillin, cefotaxime, ceftazidime, ceftriaxone, aztreonam, imipenem, gentamicin, amikacin, netilmicin, norfloxacin, and ciprofloxacin.

Antimicrobial susceptibility was determined by Bauer--Kirby disk diffusion method. Of 1073 tested bacteria, 704 (65.6%) produced beta-lactamase detectable by nitrocefin test. The highest percentage of resistant strains occurred with ampicillin (70%) followed by piperacillin (24%) and cefotaxime (19%). Lower percentages of resistant strains were found for gentamicin (10%), aztreonam (8%), netilmicin (7%), norfloxacin (5%) and amikacin (4%). Two percent of the strains were resistant to ciprofloxacin and 0.5% to imipenem.

The incidence of resistance in Klebsiella sp., Entero-bacter sp., E.coli and Proteus sp. was compared to that found among 872 strains isolated during July-Dec. 1984. In all the Enterobacteriaceae, mainly Enterobacter sp., the increase in the resistance was high for ampicillin, piperacillin and cefotaxime and lower for gentamicin.     

Antimicrobial Resistance of Gram-Negative Isolates from Intensive Care Units in Turkey: Comparison to Previous Three Years

Abstract

Resistance rates to selected antibiotics of Gram-negative bacteria isolated from intensive care units (ICU) of 16 Turkish hospitals during 1998 were evaluated and compared to data from the previous 3 years. Antibiotic susceptibilities to imipenem, ceftazidime, ceftazidime-clavulanate, cefoperazone-sulbactam, ceftriaxone, cefepime, cefodizime, cefuroxime, piperacillin-tazobactam, ticar-cillin-clavulanate, gentamicin, amikacin and ciprofloxacin were determined by Etest. A total of 1,404 isolates from 1,060 patients were collected, mainly from urinary and respiratory tracts. As in the previous 3 years, Pseudomonas spp. was the most frequently isolated Gram-negative species (29.7%), followed by Escherichia coli, Acinetobacter and Klebsiella spp. Imipenem was the most active in vitro agent (73.4% susceptible), followed by ciprofloxacin (60.6%), cefoperazone-sulbactam (58.7%), cefepime (56.7%), piperacillin-tazobactam (55.0%) and amikacin (54.7%). In 1996, a decline in susceptibility rates of all antibiotics was evident. With the exception of imipenem, resistance to which remained stable, rates somewhat increased in 1997. In 1998, susceptibility to imipenem and cefepime remained stable, amikacin resistance tended to increase and susceptibility rates to other antibacterials showed a favorable increase. These results may in part be due to the implementation of a surveillance program and increased understanding of the magnitude of the resistance problem.     

Comparative In Vitro Activity of Cefepime against Nosocomial Isolates

Abstract

Cefepime, a new parenteral cephalosporin, was evaluated for its In Vitro antibacterial activity in comparison with other broad-spectrum antibiotics against a total of 445 recently isolated microorganisms of nosocomial origin. Cefepime was highly active against all species of Enterobacteriaceae with minimum inhibitory concentrations (MIC₉₀s) ranging from 0.25-8 μ/ml. Cefepime showed moderate activity against Acinetobacter spp (MIC₅₀ and MIC₉₀, 16 μ/ml) but its activity was superior to that of any drug tested, except imipenem. Against Pseudomonas aeruginosa its activity was comparable to that of ceftazidime and was greater than that of cefotaxime, aztreonam, ciprofloxacin and aminoglycosides. Of all the agents tested, imipenem was the most active compound. Cefepime was active against Staphylococcus aureus and coagulase-negative methicillin-susceptible staphylococci but it had no activity against methicillin-resistant staphylococci and enterococci.     

In-vitro susceptibility of clinical isolates of Pseudomonas aeruginosa to beta-lactam and aminoglycoside antibiotics

The in-vitro susceptibilities of 198 isolates of Pseudomonas aeruginosa from clinical human specimens were determined by an agar dilution technique against beta-lactams and aminoglycosides. These isolates were susceptible to imipenem, aztreonam and ceftazidime with the minimum inhibitory concentration (MIC) for 90% of the strains tested being 8, 16 and 8 micrograms/ml, respectively. Aminoglycosides, except amikacin, had low activity (MIC90 greater than 128 micrograms/ml).     

Antimicrobial Susceptibility Patterns in Pseudomonas aeruginosa:Data from a Multicenter Intensive Care Unit Surveillance Study (ISS) in the United States

Abstract

The objectives of this study were to analyze susceptibility rates and patterns in Pseudomonas aeruginosa isolates from patients in intensive care units (ICU). A total of 2209 isolates in 1995/1996 and 2672 in 2001/2002 were tested at United States sites participating in the ICU Surveillance Study. In both periods, of the agents tested, amikacin was the most active and ciprofloxacin, the least. Resistance to common antipseudomonal agents tested increased from 1995/1996 to 2001/2002; the rise was least for amikacin (2%) and greatest for ciprofloxacin (16%). The proportion of isolates susceptible to all six antipseudomonal agents tested since 1996 decreased from 60.4% to 48.9% in 2001/2002. Examination of MIC distributions for the two periods showed that for some drugs, e.g. imipenem and ceftazidime, the populations of susceptible and resistant isolates remained distinct, although the resistant population increased. For other drugs, e.g. amikacin and piperacillin-tazobactam, the MIC distribution shifted upward over time. The categorical agreement between agents of the same or like classes for isolates tested in 2001/2002 was highest for ciprofloxacin and levofloxacin (93.2%, with 1.2% major errors) and lowest for the aminoglycosides (81.3%, with 10.2% major errors). We can conclude that resistance to antipseudomonal agents among ICU isolates of P. aeruginosa, especially fluoroquinolones, is increasing. The resistance rate for some antipseudomonal agents may not accurately reflect shifts in the MIC distribution curve.     

Surveillance of antimicrobial resistance in gram-negative isolates from intensive care units in Turkey: analysis of data from the last 5 years

A multicenter antimicrobial surveillance program was established in Turkey in 1995 to monitor the predominant Gram-negative pathogens from intensive care units (ICUs) and antimicrobial resistance patterns of these isolates. Sixteen hospitals participated in the study and a total of 1479 isolates from 1,100 patients were collected. The isolates were tested for their susceptibility against 13 antibiotics by E-test method. Minimum inhibitory concentrations (MICs) for each isolate were determined for imipenem, ceftazidime, ceftazidime-clavulanate, cefoperazone-sulbactam, ceftriaxone, cefepime, cefuroxime, piperacillin-tazobactam, ticarcillin-clavulanate, gentamicin, amikacin and ciprofloxacin. The most common isolates were Pseudomonas spp. (28.2%), Escherichia coli (19.2%) and Klebsiella spp. (19.1%). We found very high resistance rates to all major antibiotics that are used to treat serious infections. Although imipenem is the most active agent, it had an overall susceptibility rate of 68%. Half of the tested Klebsiella spp. strains were found to produce ESBL. This is a very high rate when compared with the literature. Cross-resistance among species was also investigated. 52% of ciprofloxacin-resistant strains were also resistant to imipenem, 80% to ceftazidime, 97% to ceftriaxone, 86% to amikacin and 19% of imipenem-resistant strains were susceptible to ceftazidime and 18% to amikacin. When susceptibilities of the years 1995 and 1999 were compared, the most interesting finding was the decrease in resistance to 3rd generation cephalosporins. In conclusion, this national clinical isolate database shows that resistance rates are high, the change over years is not predictable and continuous surveillance is necessary to monitor antimicrobial resistance and to guide antibacterial therapy.     

Imipenem and Cefotaxime Resistance: Transduction by Wild-Type Phages in Hospital Strains of Pseudomonas aeruginosa

Summary

A wild-type bacteriophage appeared and was isolated from a Pseudomonas aeruginosa strain resistant to imipenem, cefotaxime, kanamycin and streptomycin (susceptible to carbenicillin, aztreonam, amikacin and fluoroquinolones). The best transducing properties were obtained with phage lysates prepared from bacteria growing on cefotaxime or imipenem. Transducing properties were found specific for individual recipient strain(s) susceptible to all drugs. A high-frequency of transduction was recorded for kanamycin and particularly for cefotaxime resistance determinants, followed by an imipenem determinant. This is now the fourth published wild-type bacteriophage, isolated from lysogenic nosocomial P. aeruginosa resistant to imipenem which was found to transduce this resistance determinant to susceptible pseudomonads.     

A Comparative Study on Aztreonam,Ceftazidime and Amikacin in the Treatment of Complicated Urinary Tract Infections

Summary

In a prospective, randomized trial, aztreonam (1 g intravenously or intramuscularly, twice daily) was compared with ceftazidime (1 g intravenously or intramuscularly, twice daily) and amikacin (500 mg intravenously or intramuscularly, twice daily) in 76 patients aged 24 to 84 years (mean, 59.7 years) with complicated urinary tract infections. Initial pathogens included Escherichia coli (47.5%), Pseudomonas aeruginosa (22.5%), Klebsiella spp. (9%), Proteus spp. (7.5%) and Enterobacter spp (6%). In four patients initial urine cultures yielded more than one organism. All pathogens were sensitive to the three study drugs. Including performance of 4- to 6-week follow-up cultures, eradication of the pathogens occurred in 72% of patients treated with aztreonam, in 74% of those treated with ceftazidime and in 71% treated with amikacin (p>0.05). Clinical success was observed in 84% of patients treated with aztreonam, in 82% of those treated with ceftazidime and in 85% treated with amikacin (p>0.05). All drugs were well tolerated. It is concluded that aztreonam, ceftazidime and amikacin are equally effective and safe for the treatment of complicated urinary tract infections due to susceptible organisms.     

The Minimum Inhibitory Concentration of Seventeen Antimicrobials for Salmonella Isolates from Septic Patients

Abstract

Herein we are reporting, for the first time in Kuwait, the minimum inhibitory concentrations (MICs) of Salmonella blood culture isolates vs. 17 clinically relevant antimicrobial agents. The screening of blood culture specimens was performed with the most advanced Bactec 9240 (Becton Dickinson). From over 20,000 blood cultures, 112 Salmonella isolates were obtained from 67 patients. Their MICs were determined using the automated Vitek microdilution technique (Biomerieux Vitek Inc.). During the whole 1991-1995 study period, the MICs for cefotaxime, ceftazidime, aztreonam, amikacin, gentamicin, ciprofloxacin and imipenem were below their respective susceptibility breakpoints. Resistance to chloramphenicol, ampicillin and cotrimoxazole varied from year to year, from 18% to 50%, except in 1991 when it was nil (1991 was the first year after the Gulf War, with very few newcomers from the Indian subcontinent). All ampicillin-susceptible S. typhi isolates had extremely low MIC values (≤0.25 μg/ml).     

In Vitro Bactericidal Effect of a β-lactam + Aminoglycoside Combination Against Multiresistant Pseudomonas aeruginosa and Acinetobacter baumannii

Abstract

Pseudomonas aeruginosa and Acinetobacter baumannii are frequently isolated in hospital outbreaks of nosocomial infections. In our hospital, among 1018 strains isolated one year in an intensive care unit, 84 strains (8.3%) of P. aeruginosa and 155 strains (15.2%) of A. baumannii were considered responsible for infections. The major problem related to these bacteria is their multiresistant characteristic which confers great difficulty in treating infections. We carried out a 24 h time-kill study to assess the bactericidal effect of three β-lactams [imipenem (IPM), ticarcillin + clavulanic acid (TCC), piperacillin + tazobactam (PTB)] in combination with each other and with sulbactam (SUL) and amikacin (AKN) against 8 P. aeruginosa strains and 8 A. baumannii strains. The initial inoculum was 10⁶ cfu/ml. Antibiotics were tested at clinically achievable concentrations: TCC (112 mg/l), PTB (100 mg/l), IPM (25 mg/l) and AKN (15 mg/l). The results showed: IMP+TCC+AKN = PTB+SUL+AKN = PTB+TCC+ AKN >> IMP+SUL+AKN against P. aeruginosa; and PTB+SUL+AKN = PTB+TCC+AKN > IMP+SUL+AKN or IMP+TCC+AKN against A. baumannii. When infection due to these multiresistant strains was suspected, PTB+AKN combined with either TCC or SUL was bactericidal against both strains. These combinations appeared to be an alternative therapy in the treatment of undocumented nosocomial infections in intensive care units. These In Vitro results are being evaluated in patients and seem to give good results for the moment.     

Susceptibility of 228 Non-fermenting Gram-Negative Rods to Tigecycline and Six Other Antimicrobial Drugs

Abstract

The aim of the study was to determine the in vitro activity of tigecycline and 6 other antimicrobial drugs used in clinical practice against 228 clinical isolates of nonfermenting Gram-negative rods (NFGNRs) including Acinetobacter spp. Stenotrophomonas maltophilia, and Pseudomonas aeruginosa. Minimum inhibitory concentrations (MICs) were determined according to the recommendations of the Clinical and laboratory Standards institute. For tigecycline, we used the criteria approved by the FDA. Almost 50% of the clinical isolates of Acinetobacter spp. were resistant to piperacillin/tazobactam, ciprofloxacin, gentamicin, and ceftazidime. Strains of this microorganism were more susceptible to imipenem, and even more susceptible to colistin and tigecycline; no strains were resistant to tigecycline. Stenotrophomonas maltophilia showed even greater resistance to the drugs tested. Thus, all strains were resistant to imipenem and a large percentage (82.6%) were resistant to piperacillin/tazobactam. Resistance to the other agents tested was also high, with the exception of tigecycline, with only 3 resistant strains (MIC <8 mg/ml). Tigecycline, on the other hand, was scarcely active against Pseudomonas aeruginosa, which bears efflux pump systems such as MexXY-OprM. Almost 90% of strains were resistant to ciprofloxacin; only 8% were resistant to gentamicin; over half were colistin-intermediate or -resistant, and finally, approximately half of the strains were susceptible to the 3 beta-lactams studied. In conclusion, NFGNRs present variable susceptibility patterns, although they are generally highly resistant to antimicrobial agents including those considered more specific. Tigecycline, which showed good activity against most of the strains examined, broadens the spectrum of drugs available for the treatment of infections caused by these complex microorganisms.     

Multidrug-Resistant Acinetobacter baumannii Outbreak in an Intensive Care Unit

Abstract

Carbapenem-resistant Acinetobacter baumannii was isolated from 15 colonized or infected patients (carriers) between April and July 2004, in a teaching hospital ICU in Rome, Italy. All isolated strains were susceptible only to gentamicin, ampicillin-sulbactam and colistin and displayed the same Random Amplified Polymorphic DNA (RAPD) 1 pattern. Twelve out of 15 strains were susceptible to tigecycline, whereas the remaining three showed intermediate susceptibility. Although infection control measures were reinforced and carriers isolated in separate rooms, A. baumannii transmission continued. Therefore, finally A. baumannii carriers were moved to another available subintensive unit, which was re-equipped, and cared for by dedicated personnel, whereas only the non infected/colonized patients remained in the ICU. This study shows that during an outbreak by multiresistant A. baumannii it may be indispensable to geographically isolate not only patients but also dedicated staff.     

In-Vitro Susceptibility of Clinical Isolates of Serratia Species to Antimicrobial Agents

Summary

The in-vitro activities of 12 antimicrobial agents against a total of 80 clinical isolates of Serratia marcescens and Serratia liquefaciens were determined by a broth microdilution method. Ampicillin and cefazolin were totally inactive against these organisms. The other β-lactam antibiotics such as piperacillin, cefotaxime, ceftazidime, and the aminoglycosides such as gentamicin, tobramycin and netilmicin showed poor or moderate activity against Serratia isolates. Aztreonam and amikacin inhibited most of the strains tested. Imipenem and ciprofloxacin were very active in inhibiting all strains. Within the genus, S. liquefaciens was more resistant to aztreonam, ceftazidime and amikacin than S. marcescens.