17 December 2020

Clinical and Economic Impact of Common Multidrug-Resistant Gram-Negative Bacilli

Authors: Christian G. Giske chris[email protected], Dominique L. Monnet, Otto Cars, Yehuda Carmeli, on behalf of ReAct-Action on Antibiotic Resistance
During the last decade, the efforts to combat multidrug-resistant (MDR) microorganisms mainly focused on gram-positive bacteria, namely, methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. While a large number of hospitals have implemented more rigorous infection control measures, drug companies have developed novel antimicrobial agents to combat these bacteria, resulting in several new compounds with novel mechanisms of action, e.g., linezolid and daptomycin (66). Paralleling the developments in gram-positive bacteria, infections caused by MDR gram-negative bacilli have become a growing problem (71). In a recent report the Infectious Diseases Society of America specifically addressed three categories of MDR gram-negative bacilli, namely, extended-spectrum cephalosporin-resistant Escherichia coli and Klebsiella spp., MDR Pseudomonas aeruginosa, and carbapenem-resistant Acinetobacter spp. (70). Unfortunately, and contrary to what happened with gram-positive bacteria, no antibiotic from a new class has been developed specifically for MDR gram-negative bacilli. It might be argued that the glycylcycline tigecycline is an exception from the statement made above, but although this drug has in vitro activity against many MDR gram-negative bacilli, the drug was not developed specifically for the purpose of treating infections caused by such bacteria (64). Moreover, there are now a growing number of reports of cases of infections caused by gram-negative organisms for which no adequate therapeutic options exist (20). This return to the preantibiotic era has become a reality in many parts of the world (14, 55, 80). The present report aims at estimating the prevalence of infections due to MDR gram-negative bacilli, as well as the consequences with respect to mortality, hospital length of stay (LOS), and increased hospital costs.
The topics covered in this report are resistance to extended-spectrum cephalosporins in E. coli and Klebsiella pneumoniae, MDR (resistance to three or more antipseudomonal agents) (17) in P. aeruginosa, and carbapenem resistance in Acinetobacter spp. PubMed (; accessed on 31 October 2007) searches were performed by using the following search terms: (Escherichia coli OR Klebsiella pneumoniae) AND ESBL, (Escherichia coli OR Klebsiella pneumoniae) AND cephalosporin resistance, Pseudomonas AND multidrug resistance, Acinetobacter AND carbapenem resistance, antibiotic resistance AND (Pseudomonas OR Acinetobacter OR Escherichia coli OR Klebsiella) AND mortality, antibiotic resistance AND (Pseudomonas OR Acinetobacter OR Escherichia coli OR Klebsiella) AND length of stay, and antibiotic resistance AND (Pseudomonas OR Acinetobacter OR Escherichia coli OR Klebsiella) AND cost. The searches were performed to address the issues of prevalence, mortality, increased LOS, and increased hospital costs. Following the review of all abstracts, a total of 85 papers were considered relevant and were evaluated for the preparation of this report. All included papers on the clinical and economic impact of gram-negative bacilli included proper control groups. Only papers published in English were considered.


Among the species E. coli and K. pneumoniae, a worrisome trend during the last two decades has been the development of resistance to extended-spectrum cephalosporins, e.g., cefotaxime, ceftazidime, and ceftriaxone (54). Such resistance is most often due to the breakdown of the extended-spectrum cephalosporin by extended-spectrum β-lactamases (ESBLs), but it may also be due to plasmid-mediated or chromosomally hyperproduced AmpC (46). Depending on the breakpoint system used, certain ESBLs may not always be detected and classified as resistant to all cephalosporins; however, with the current European Committee on Antimicrobial Susceptibility Testing breakpoints (, ESBL-producing isolates are usually resistant to at least one extended-spectrum cephalosporin (72). The genes encoding the ESBLs are found on plasmids and have a great propensity to spread between bacteria (8).
Resistance to fluoroquinolones, co-trimoxazole, and trimethoprim is frequently observed among ESBL producers (15, 69). Thus, the presence of an ESBL is a good marker of the MDR phenotype. The carbapenems, i.e., imipenem, meropenem, and ertapenem, are considered the drugs of choice for the treatment of infections caused by extended-spectrum cephalosporin-resistant E. coli and K. pneumoniae; however, carbapenem resistance is emerging in certain geographic areas (27, 43, 52, 54, 79). The tetracycline derivative tigecycline has promising in vitro activity against many of these MDR organisms; but the clinical experience with this agent is still limited (48), and low-grade tigecycline resistance in members of the family Enterobacteriaceae has been reported and has been attributed to efflux pump mechanisms (32, 58, 65).

Prevalence of resistance.

The rates of resistance to extended-spectrum cephalosporins in E. coli and K. pneumoniae in various parts of the world are summarized in Table 1. Although statistics from many parts of the world are unavailable, accumulating evidence still suggests that resistance to extended-spectrum cephalosporins in E. coli and, in particular, K. pneumoniae has become a worldwide problem (55), with only certain areas in the United States and northern Europe being relatively spared. Also, the recently described dissemination of ESBL-producing Enterobacteriaceae in the community poses a new threat, since this may become a powerful reservoir for the continued influx of resistant strains into hospitals (3, 60).

Impact of resistance on mortality, LOS, and hospital costs.

A total of 14 papers were considered, and of these, 8 papers found an impact on resistance to extended-spectrum cephalosporins (in most cases caused by ESBL production) on one or several of the three outcome variables, mortality, LOS, and increased hospital cost. The findings from these papers are displayed in Table 2. Six of the papers describe the impact on resistance to extended-spectrum cephalosporins in patients with bloodstream infections, while the rest of the papers considered various types of nosocomial infections. All of the studies are retrospective cohort studies; nine of the studies used either matched controls or multivariate analysis, in order to minimize residual confounding; but only a few of them feature matched controls, an approach that is recommended when the source populations for resistant and susceptible cases are different (37). Lastly, all except two studies found in this collection were single-center studies, indicating that local epidemiological factors may be of importance for the reported findings.
The impact of ESBL production on mortality from bacteremia caused by Enterobacteriaceae has been studied in a recent meta-analysis by Schwaber et al. (67), and a significantly increased rate of mortality was found in the ESBL group (pooled relative risk [RR], 1.85; 95% confidence interval [CI], 1.39 to 2.47). The same study demonstrated an increased RR for delayed effective therapy (pooled RR, 5.36; 95% CI, 2.73 to 10.53). The increased mortality observed in patients with bloodstream infections (BSIs) can be contrasted with the findings of eight additional studies, all of which also included patients with types of infections other than BSIs. Among those studies, increased mortality was found in only one, although a tendency toward a higher rate of mortality in the ESBL group could be observed in some of the studies. Six of seven studies found increased LOSs for patients with extended-spectrum cephalosporin-resistant isolates, while increased cost was found in the three studies that considered this parameter.


MDR in P. aeruginosa is usually defined as resistance to three or more of the following antimicrobial agents: antipseudomonal penicillins (e.g., piperacillin), antipseudomonal cephalosporins (e.g., ceftazidime), fluoroquinolones (e.g., ciprofloxacin), carbapenems (imipenem, meropenem, and doripenem), and the aminoglycosides (gentamicin, tobramycin, or amikacin) (17). Resistance is often caused by the interplay of various resistance mechanisms, including β-lactamases, aminoglycoside-modifying enzymes, topoisomerase mutations, decreased permeability, and the activities of efflux pumps (6). The presence of the emerging transmissible metallo-β-lactamases (MBLs) can in itself confer an MDR phenotype, since these β-lactamases can hydrolyze all β-lactams except aztreonam (80). Also, due to the collocation of genes encoding MBLs and aminoglycoside-modifying enzymes on mobile genetic elements, such isolates are also frequently resistant to aminoglycosides (80).

Prevalence of resistance.

Although an abundance of studies have covered susceptibility to various antibiotics in P. aeruginosa, relatively few studies have examined the prevalence of MDR, defined as resistance to three or more antipseudomonal agents. One possible explanation for this could be the absence of an international consensus regarding the definition of MDR in P. aeruginosa (22). The resistance rates in various parts of the world are displayed in Table 3.

Impact of resistance on mortality, LOS, and hospital costs.

Due to the different definitions of the MDR phenotype in P. aeruginosa, the data on the clinical and economic impact of resistance (Table 4) cannot easily be directly compared. Six studies found an impact on mortality and one found an impact on LOS, but in all of these studies the isolates were resistant to four or more antipseudomonal drugs. One study found no impact of the MDR phenotype on the outcome, but the isolates in that study were resistant to only two or more antipseudomonal antibiotics. Two of the studies showing an impact of the MDR phenotype on the outcome did not apply matched controls or multivariate analysis (37), and in one of the studies the impact detected in the univariate analysis disappeared in the multivariate analysis, indicating that factors other than the resistance phenotype were important for the outcome (85). Also, three of the studies showing an impact of the MDR phenotype on the outcome compared MBL-producing isolates with MBL-negative isolates, and MDR isolates were also present in the control groups. None of the studies were multicenter studies.
In addition to the studies presented in Table 4, a recent case-control study showed an impact of fluoroquinolone-resistant P. aeruginosa on mortality and hospital costs (26). The fluoroquinolone-resistant isolates in that study were also resistant to one to two other classes of drugs; i.e., some of them had an MDR phenotype. In the multivariate analysis performed in the same study, only imipenem resistance was associated with increased mortality. The imipenem-resistant isolates in the study were also resistant to a median of three other classes of drugs, implying that all of the isolates in this group were in fact MDR isolates.


Acinetobacter spp. are frequently resistant to fluoroquinolones, aminoglycosides, and all β-lactams, with the exception of the carbapenems; and carbapenems are therefore often increasingly considered the drugs of choice for the treatment of infections due to Acinetobacter spp. (51). However, carbapenem resistance in Acinetobacter spp. is emerging in many parts of the world (10), mainly due to carbapenemases and, possibly, other mechanisms, such as alterations of outer membrane proteins (6). Although these multiresistant Acinetobacter spp. may still retain susceptibility to the polymyxins (i.e., colistin and polymyxin B), sulbactam, and possibly tigecycline, panresistant isolates that are resistant to all available drugs are now being reported (20).

Prevalence of resistance.

Although Acinetobacter spp. are the causative agents of BSIs, as well as other infections, less often than E. coli, Klebsiella spp., and P. aeruginosa are (5), their occurrence is increasing dramatically (57). The frequently observed multiresistance of Acinetobacter sp. isolates complicates antibiotic therapy. A recent study has reported an average rate of carbapenem resistance of 27% among Acinetobacter spp. in European countries (78). Another study covering three continents, including Europe, reported an average rate of carbapenem resistance of 16% among Acinetobacter spp. (23). These high levels of resistance make polymyxins the drugs of last resort for the treatment of infections due to multiresistant Acinetobacter spp. (21). The resistance rates in various parts of the world are summarized in Table 5.

Impact of resistance on mortality, LOS, and hospital costs.

Six studies were considered relevant for inclusion in this report on the clinical impact of carbapenem-resistant Acinetobacter spp., and two of these studies were conducted with burn patients (Table 6). The only study performed with patients with BSIs found significantly increased rates of mortality in the group of patients infected with carbapenem-resistant Acinetobacter spp. (39). Also, a study of nosocomial intensive care unit (ICU) infections found a significantly higher rate of mortality among patients infected with carbapenem-resistant Acinetobacter spp., and the same study also showed a significantly increased LOS (61). One case-control study of nosocomial infections found no significant differences in the rates of mortality between patients infected with carbapenem-resistant and -susceptible isolates but a more than twofold increase in hospital LOS (9). Among the two studies of burn patients, one found increased rates of mortality and LOSs (82), while one study detected only increased costs (81). One case-control study of nosocomial infections caused by multiresistant Acinetobacter spp., P. aeruginosa, and S. aureus did not meet the criteria for inclusion in this report. MDR Acinetobacter spp. were defined as being resistant to aminoglycosides, quinolones, and extended-spectrum cephalosporins; and Acinetobacter spp. were the dominant MDR pathogens among the case patients. The mortality rate was significantly higher for the cases than for the controls (27% and 12.7%, respectively; P < 0.01), although susceptibility to carbapenems was allowed in the case group (16).


For the members of the family Enterobacteriaceae, a recent meta-analysis has found increased rates of mortality among patients with BSIs caused by ESBL-producing organisms (67), while a majority of studies of other types of infections found no significant differences attributable to resistance to extended-spectrum cephalosporins. This finding is not surprising, partly since the presence of Enterobacteriaceae in other specimens may represent colonization rather than infection and partly because the overall rate of mortality among patients with non-BSIs caused by Enterobacteriaceae is generally low. The reason for the increased rate of mortality among patients with BSIs caused by ESBL-producing organisms seems to be a delay in effective treatment (2, 47, 75). With respect to the other parameters considered in this review, the currently available literature shows both increased LOSs and increased costs attributable to resistance to extended-spectrum cephalosporins in the Enterobacteriaceae. The trend toward the development of carbapenem resistance in the Enterobacteriaceae is of major concern, but the clinical and economic impact remains to be studied.
The absence of an accepted international definition of MDR P. aeruginosa poses a problem when the impact of such resistance is estimated. Most of the studies considered in this report defined MDR as resistance to four or more antipseudomonal agents. If this criterion is applied, six studies indicate that increased mortality and one study indicated that increased LOSs were attributable to MDR P. aeruginosa. No studies addressing attributable costs could be identified. Three of the studies showing an impact of MDR P. aeruginosa on mortality featured isolates producing MBL in the case groups. Hence, it could be debated whether the observed effect was due to the MDR phenotype or whether it was related to other features of the MBL-producing isolates. For MDR P. aeruginosa strains, the polymyxins are still possible treatment alternatives, but resistance to these agents has also been described (20).
Six studies regarding the clinical impact of carbapenem-resistant Acinetobacter spp. were identified. One study of BSIs caused by Acinetobacter spp. identified carbapenem resistance as a risk factor for mortality (39). A similar observation was done in a study of ICU patients, in which increased rates of mortality and increased hospital LOSs were seen (61). One additional study of mixed infections found an impact on mortality, but generally, the number of patients in that study was low and the question of infection versus colonization was not properly addressed (82). Apart from the study of ICU patients, two other studies found an impact of MDR on hospital LOSs, and one study of burn patients found a substantial attributable cost. For carbapenem-resistant Acinetobacter spp., the polymyxins are the drugs of choice, although sulbactam and tigecycline have been proposed as possible treatment alternatives (45, 49). Regarding tigecycline, a cautionary report on two cases of the emergence of bloodstream infections caused by tigecycline-resistant A. baumannii during monotherapy with tigecycline was recently published; in both cases the patients were started on tigecycline for other indications (59). By taking into account the low serum concentration obtained with tigecycline (with an area under the concentration-time curve of approximately 5 mg·h/liter and a suggested pharmacodynamic target free area under the concentration-time curve/MIC of 12.5), one would reach the pharmacodynamic target only with tigecycline MICs of ≤0.25 mg/liter (19). Since wild-type isolates have MICs up to 1 mg/liter, therapeutic failures are likely to occur, at least if the drug is administered as monotherapy.
Considering the absence of an internationally accepted definition of the term MDR gram-negative bacilli, the development of an international standard for the terminology could be useful. Two adjectives have previously been used to define gram-negative bacilli that are resistant to several agents: MDR and pandrug resistant (PDR). Recently, Paterson and Doi have suggested the use of the term “extreme drug resistance” and the abbreviation “XDR” to complement the two previous terms (56). The same paper suggests that PDR should be used to designate gram-negative bacilli that are resistant to all authorized antimicrobial agents except tigecycline and the polymyxins and that the use of XDR should be restricted to bacteria that are also resistant to the latter two drugs. Although a standardized terminology is needed, it could be debated whether this use of PDR and XDR is optimal. Semantically, PDR would be an appropriate term for bacteria that are resistant to all authorized agents, a point that has also been made by Falagas et al. (22). Additionally, XDR is already defined internationally as “extensively drug resistant” and introduction of the term “extreme drug resistance” may create confusion (12). An alternative option would therefore be to use the term “extensively drug-resistant” (XDR) for gram-negative bacilli resistant to all authorized agents except tigecycline and the polymyxins, whereas PDR would be restricted to application to truly PDR bacteria. Attempts to reach an international consensus on definitions should be made, since this will greatly enhance the comparabilities of future studies of resistant gram-negative bacilli and thereby also facilitate future meta-analyses within this field.


Current evidence suggests that infections caused by ESBL-producing Enterobacteriaceae are associated with increased hospital LOSs and costs. Also, BSIs caused by ESBL-producing Enterobacteriaceae are associated with increased rates of mortality. MDR P. aeruginosa (resistance to four or more antipseudomonal agents) is associated with increased mortality and increased hospital LOSs. For Acinetobacter spp., BSIs and nosocomial ICU infections caused by carbapenem-resistant isolates are associated with increased rates of mortality. Other types of infections have not clearly been shown to be associated with higher rates of mortality but are associated with increased LOSs and hospital costs. The clinical and economic impact of MDR gram-negative bacilli is substantial and greatly worrisome. An international agreement on the definitions of such bacteria could potentially facilitate an orchestrated response against these pathogens.
TABLE 1. Prevalence of resistance to extended-spectrum cephalosporins in E. coli and K. pneumoniae in various parts of the world
RegionPeriodSettingResistance (%) Reference
   K. pneumoniaeE. coli 
North America     
    United States2003ICU20.65.850
    United States2004Intra-abdominal infections5.32.863
    United States (Brooklyn)2006All infections59 40
Latin America     
    Seven countries2000Urinary tract infections22.33.125
    Ten countries2004Intra-abdominal infections27.612.063
    Northern Europe2000-2001Nosocomial infections5.21.47
    Southern Europe2000-2001Nosocomial infections25.76.67
    Nine countries2004Intra-abdominal infections8.86.463
    China1998-2002Nosocomial infections37.331.330
    Japan1998-2002Nosocomial infections11.06.530
    Singapore1998-2002Nosocomial infections36.412.330
Oceania (Australia)1998-2002Nosocomial infections4.61.630
South Africa1998-2002Nosocomial infections29.61.930
TABLE 2. Impact of extended-spectrum cephalosporin resistance in Enterobacteriaceae on mortality, LOS, and hospital cost
Type of studySettingType of infectionBacteriaNo. of cases/no. of controlsParameterMain findingsSignificance (P value or 95% CI)Reference
Studies showing an impact of resistance        
    Case-controlTertiary careNosocomialE. coli and K. pneumoniae33/66aLOSCases, 1.76 times greater duration1.17-2.6442
     Increased costCases, 2.90 times higher cost1.76-4.78 
    Case-controlTertiary careBSIK. pneumoniae44/118aLOSCases, 39.6 days; controls, 23.9 daysP < 0.00838
    Case-controlMulticenterNosocomialK. pneumoniae9/9MortalityCases, 44%; controls, 33%P > 0.059
     LOSCases, 37 ± 25 days; controls, 15 ± 10 daysP = 0.04 
    Case-controlTertiary carePeritonitis (CAPDb)E. coli11/77MortalityCases, 27.3%; controls, 3.9%P = 0.0283
    Retrospective cohortTertiary careBSIEnterobacteriaceae99/99aLOSCases, 1.56 greater durationP = 0.00168
     Increased costCases, 1.57 times higher costP = 0.003 
    Retrospective cohortTertiary careNon-urinary tractE. coli and Klebsiella spp.21/21aMortalityCases, 8%; controls, 14%P = 0.18244
     LOSCases, 21 days; controls, 11 daysP = 0.006 
     Increased costAttributable cost, $16,450$965-31,937 
    Retrospective cohortTertiary careBSIK. pneumoniae46/82aMortalityORc for death in cases, 2.661.07-6.5976
     LOSCases, 22 days; controls, 16 daysP = 0.03 
    Prospective cohortTertiary careBSIE. coli46/308aMortalityOR for death in cases, 3.571.48-8.6047
Studies showing no impact of resistance        
    Case-controlTertiary careNosocomialEnterobacteriaceae23/174MortalityCases, 26%; controls, 16%P = 0.1418
    Case-controlTertiary careNosocomialK. pneumoniae60/60a, dMortalityCases, 30%; controls, 28.3%P = 0.084133
    Case-controlTertiary careNosocomialEnterobacteriaceae31/39MortalityCases, 3.0%; controls, 2.4%P > 0.0513
    Case-controlTertiary careBSIE. coli and35/105aLOSCases, 8.2 additional daysP = 0.18284
   Klebsiella spp.     
    Retrospective cohortTertiary careNosocomialK. pneumoniae68/75aMortalityRRe, 0.940.45-1.9728
    Prospective cohortMulticenterBSI or pneumoniaEnterobacteriaceae135/40MortalityCases, 5.2%; controls, 12.5%P = 0.154
Studies with either matched controls or multivariate analysis, in order to minimize confounding.
CAPD, continuous ambulatory peritoneal dialysis.
OR, odds ratio.
Matched controls.
RR, risk ratio.
TABLE 3. Prevalence of MDR among P. aeruginosa strains in various parts of the world
RegionPeriodSettingResistance (%)Reference
North America    
    United States2001ICU/non-ICU9.1/7.035
    United States2002ICU1435
    United States2003Nosocomial infections9.936
South America, 10 sites1997-1999Nosocomial infections8.224
    12 to 23 sites1997-1999Nosocomial infections4.724
    33 ICUs1997-2000ICU3-5029
    17 sites1997-1999Nosocomial infections1.624
    Japan2001Nosocomial infections2.874
    Malaysia2005Nosocomial infections6.962
TABLE 4. Impact of the MDR phenotype in P. aeruginosa on mortality, LOS, and hospital cost
Type of studySettingInfectionNo. of cases/no. of controlsParameterMain findingsSignificance (P value or 95% CI)Reference
Studies showing an impact of resistance       
    Case-controlTertiary careNosocomial69/247MortalityOR,a 5.01.1-22.931
    Retrospective cohortTertiary careNosocomial44/68b, cMortalityCases, 54.5%; controls, 16.2%P < 0.0511
    Case-controlTertiary careBSI6/184b, cMortalityCases, 83.3%; controls, 36.4%P = 0.0334
    ProspectiveTertiary careNosocomial/98/103MortalityRR, 1.981.0-3.941
    ProspectiveTertiary careNosocomial86/212cMortalityRR, 1.601.2-2.1d85
    Retrospective matched cohortTertiary careNosocomial82/82b, c, eMortalityOR, 4.4P = 0.041
Retrospective cohort study showing no impact of resistanceTertiary careNoscomial18/35c, fMortalityCases, 22%; controls, 23%P > 0.0553
OR, odds ratio.
MDR was defined as resistance to four or more antibiotics.
Studies with either matched controls or multivariate analysis, in order to minimize confounding.
Not significant in multivariate analysis.
Matched controls.
MDR was defined as resistance to two or more antibiotics.
TABLE 5. Prevalence of carbapenem resistance in Acinetobacter spp. in various parts of the world
RegionPeriodSettingResistance (%) Reference
North America     
    15 centers2002-2004Nonduplicate clinical isolates8.36.578
    24 centers2001Non-ICU isolates6.110.435
    15 centers2006All isolates335340
South America     
    25 centers2002-2004Nonduplicate clinical isolates28.128.578
    7 countries2001Nonduplicate clinical isolates16.318.173
    48 centers2002-2004Nonduplicate clinical isolates30.226.978
    37 centers1997-2000Nonduplicate clinical isolates161477
Asia/Pacific, 2 centers2002-2004Nonduplicate clinical isolates1.26.078
Australia1999-2004Nonduplicate clinical isolates111178
TABLE 6. Impact of carbapenem resistance in Acinetobacter spp. on mortality, LOS, and hospital costs
Type of study showing an impact of resistanceSettingInfectionNo. of cases/no. of controlsParameterMain findingsSignificance (P value or 95% CI)Reference
Case-controlTertiary careNosocomial10/10MortalityCases, 34%; controls, 27%P > 0.059
    LOSCases, 31.5 days; controls, 13 daysP = 0.02 
Case-controlTertiary careBurn patients34/43MortalityCases, 26.5%; controls, 0%P < 0.0182
    LOSCases, 32.5 days; controls 21 daysP < 0.01 
Case-controlTertiary careBurn patients34/183LOSCases, 36.8 days; controls, 25.6 daysP = 0.0681
    CostCases, $98,575 higherP < 0.01 
Case-controlTertiary careBSI40/40aMortalityCases, 57.5%; controls, 25.7%P = 0.00739
Case-controlICUNosocomial infections34/68aMortalityOR,b 3.91.4-10.761
    LOSCases, 30 days longer11-38 days 
Case-controlICUColonization32/63aLOS (ICU)Cases, 19 days longer5-28 days61
Studies with either matched controls or multivariate analysis, in order to minimize confounding.
OR, odds ratio.


The work related to this paper was supported financially by ReAct (Action on Antibiotic Resistance;, an international coalition supported by the Swedish International Development Cooperation Agency.


Aloush, V., S. Navon-Venezia, Y. Seigman-Igra, S. Cabili, and Y. Carmeli.2006. Multidrug-resistant Pseudomonas aeruginosa: risk factors and clinical impact. Antimicrob. Agents Chemother.50:43-48.
Anderson, D. J., J. J. Engemann, L. J. Harrell, Y. Carmeli, L. B. Reller, and K. S. Kaye.2006. Predictors of mortality in patients with bloodstream infection due to ceftazidime-resistant Klebsiella pneumoniae. Antimicrob. Agents Chemother.50:1715-1720.
Ben-Ami, R., M. J. Schwaber, S. Navon-Venezia, D. Schwartz, M. Giladi, I. Chmelnitsky, A. Leavitt, and Y. Carmeli.2006. Influx of extended-spectrum beta-lactamase-producing Enterobacteriaceae into the hospital. Clin. Infect. Dis.42:925-934.
Bhavnani, S. M., P. G. Ambrose, W. A. Craig, M. N. Dudley, and R. N. Jones.2006. Outcomes evaluation of patients with ESBL- and non-ESBL-producing Escherichia coli and Klebsiella species as defined by CLSI reference methods: report from the SENTRY Antimicrobial Surveillance Program. Diagn. Microbiol. Infect. Dis.54:231-236.
Biedenbach, D. J., G. J. Moet, and R. N. Jones.2004. Occurrence and antimicrobial resistance pattern comparisons among bloodstream infection isolates from the SENTRY Antimicrobial Surveillance Program (1997-2002). Diagn. Microbiol. Infect. Dis.50:59-69.
Bonomo, R. A., and D. Szabo.2006. Mechanisms of multidrug resistance in Acinetobacter species and Pseudomonas aeruginosa. Clin. Infect. Dis.43(Suppl. 2):S49-S56.
Bouchillon, S. K., B. M. Johnson, D. J. Hoban, J. L. Johnson, M. J. Dowzicky, D. H. Wu, M. A. Visalli, and P. A. Bradford.2004. Determining incidence of extended spectrum beta-lactamase producing Enterobacteriaceae, vancomycin-resistant Enterococcus faecium and methicillin-resistant Staphylococcus aureus in 38 centres from 17 countries: the PEARLS study 2001-2002. Int. J. Antimicrob. Agents24:119-124.
Bradford, P. A.2001. Extended-spectrum beta-lactamases in the 21st century: characterization, epidemiology, and detection of this important resistance threat. Clin. Microbiol. Rev.14:933-951.
The Brooklyn Antibiotic Resistance Task Force.2002. The cost of antibiotic resistance: effect of resistance among Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa on length of hospital stay. Infect. Control Hosp. Epidemiol.23:106-108.
Brown, S., and S. Amyes.2006. OXA (beta)-lactamases in Acinetobacter: the story so far. J. Antimicrob. Chemother.57:1-3.
Cao, B., H. Wang, H. Sun, Y. Zhu, and M. Chen.2004. Risk factors and clinical outcomes of nosocomial multi-drug resistant Pseudomonas aeruginosa infections. J. Hosp. Infect.57:112-118.
Centers for Disease Control and Prevention.2006. Emergence of Mycobacterium tuberculosis with extensive resistance to second-line drugs—worldwide, 2000-2004. MMWR Morb. Mortal. Wkly. Rep.55:301-305.
Chiu, S., Y. C. Huang, R. I. Lien, Y. H. Chou, and T. Y. Lin.2005. Clinical features of nosocomial infections by extended-spectrum beta-lactamase-producing Enterobacteriaceae in neonatal intensive care units. Acta Paediatr.94:1644-1649.
Coelho, J., N. Woodford, J. Turton, and D. M. Livermore.2004. Multiresistant Acinetobacter in the UK: how big a threat? J. Hosp. Infect.58:167-169.
Colodner, R., Z. Samra, N. Keller, H. Sprecher, C. Block, N. Peled, T. Lazarovitch, R. Bardenstein, O. Schwartz-Harari, and Y. Carmeli.2007. First national surveillance of susceptibility of extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella spp. to antimicrobials in Israel. Diagn. Microbiol. Infect. Dis.57:201-205.
Dantas, S. R., and M. L. Moretti-Branchini.2003. Impact of antibiotic-resistant pathogens colonizing the respiratory secretions of patients in an extended-care area of the emergency department. Infect. Control Hosp. Epidemiol.24:351-355.
Defez, C., P. Fabbro-Peray, N. Bouziges, A. Gouby, A. Mahamat, J. P. Daures, and A. Sotto.2004. Risk factors for multidrug-resistant Pseudomonas aeruginosa nosocomial infection. J. Hosp. Infect.57:209-216.
Emery, C. L., and L. A. Weymouth.1997. Detection and clinical significance of extended-spectrum beta-lactamases in a tertiary-care medical center. J. Clin. Microbiol.35:2061-2067.
European Committee on Antimicrobial Susceptibility Testing (EUCAST).2006. EUCAST technical note on tigecycline. Clin. Microbiol. Infect.12:1147-1149.
Falagas, M. E., I. A. Bliziotis, S. K. Kasiakou, G. Samonis, P. Athanassopoulou, and A. Michalopoulos.2005. Outcome of infections due to pandrug-resistant (PDR) gram-negative bacteria. BMC Infect. Dis.5:24.
Falagas, M. E., and S. K. Kasiakou.2005. Colistin: the revival of polymyxins for the management of multidrug-resistant gram-negative bacterial infections. Clin. Infect. Dis.40:1333-1341.
Falagas, M. E., P. K. Koletsi, and I. A. Bliziotis.2006. The diversity of definitions of multidrug-resistant (MDR) and pandrug-resistant (PDR) Acinetobacter baumannii and Pseudomonas aeruginosa. J. Med. Microbiol.55:1619-1629.
Gales, A. C., R. N. Jones, and H. S. Sader.2006. Global assessment of the antimicrobial activity of polymyxin B against 54 731 clinical isolates of gram-negative bacilli: report from the SENTRY antimicrobial surveillance programme (2001-2004). Clin. Microbiol. Infect.12:315-321.
Gales, A. C., R. N. Jones, J. Turnidge, R. Rennie, and R. Ramphal.2001. Characterization of Pseudomonas aeruginosa isolates: occurrence rates, antimicrobial susceptibility patterns, and molecular typing in the global SENTRY Antimicrobial Surveillance Program, 1997-1999. Clin. Infect. Dis.32(Suppl. 2):S146-S155.
Gales, A. C., H. S. Sader, and R. N. Jones.2002. Urinary tract infection trends in Latin American hospitals: report from the SENTRY antimicrobial surveillance program (1997-2000). Diagn. Microbiol. Infect. Dis.44:289-299.
Gasink, L. B., N. O. Fishman, M. G. Weiner, I. Nachamkin, W. B. Bilker, and E. Lautenbach.2006. Fluoroquinolone-resistant Pseudomonas aeruginosa: assessment of risk factors and clinical impact. Am. J. Med.119:526.e19-e25.
Giakkoupi, P., A. Xanthaki, M. Kanelopoulou, A. Vlahaki, V. Miriagou, S. Kontou, E. Papafraggas, H. Malamou-Lada, L. S. Tzouvelekis, N. J. Legakis, and A. C. Vatopoulos.2003. VIM-1 metallo-beta-lactamase-producing Klebsiella pneumoniae strains in Greek hospitals. J. Clin. Microbiol.41:3893-3896.
Gomes, C. C., E. Vormittag, C. R. Santos, and A. S. Levin.2006. Nosocomial infection with cephalosporin-resistant Klebsiella pneumoniae is not associated with increased mortality. Infect. Control Hosp. Epidemiol.27:907-912.
Goossens, H.2003. Susceptibility of multi-drug-resistant Pseudomonas aeruginosa in intensive care units: results from the European MYSTIC study group. Clin. Microbiol. Infect.9:980-983.
Hirakata, Y., J. Matsuda, Y. Miyazaki, S. Kamihira, S. Kawakami, Y. Miyazawa, Y. Ono, N. Nakazaki, Y. Hirata, M. Inoue, J. D. Turnidge, J. M. Bell, R. N. Jones, and S. Kohno.2005. Regional variation in the prevalence of extended-spectrum beta-lactamase-producing clinical isolates in the Asia-Pacific region (SENTRY 1998-2002). Diagn. Microbiol. Infect. Dis.52:323-329.
Hirakata, Y., T. Yamaguchi, M. Nakano, K. Izumikawa, M. Mine, S. Aoki, A. Kondoh, J. Matsuda, M. Hirayama, K. Yanagihara, Y. Miyazaki, K. Tomono, Y. Yamada, S. Kamihira, and S. Kohno.2003. Clinical and bacteriological characteristics of IMP-type metallo-beta-lactamase-producing Pseudomonas aeruginosa. Clin. Infect. Dis.37:26-32.
Hirata, T., A. Saito, K. Nishino, N. Tamura, and A. Yamaguchi.2004. Effects of efflux transporter genes on susceptibility of Escherichia coli to tigecycline (GAR-936). Antimicrob. Agents Chemother.48:2179-2184.
Kang, C. I., S. H. Kim, D. M. Kim, W. B. Park, K. D. Lee, H. B. Kim, M. D. Oh, E. C. Kim, and K. W. Choe.2004. Risk factors for and clinical outcomes of bloodstream infections caused by extended-spectrum beta-lactamase-producing Klebsiella pneumoniae. Infect. Control Hosp. Epidemiol.25:860-867.
Kang, C. I., S. H. Kim, W. B. Park, K. D. Lee, H. B. Kim, E. C. Kim, M. D. Oh, and K. W. Choe.2005. Risk factors for antimicrobial resistance and influence of resistance on mortality in patients with bloodstream infection caused by Pseudomonas aeruginosa. Microb. Drug Resist.11:68-74.
Karlowsky, J. A., D. C. Draghi, M. E. Jones, C. Thornsberry, I. R. Friedland, and D. F. Sahm.2003. Surveillance for antimicrobial susceptibility among clinical isolates of Pseudomonas aeruginosa and Acinetobacter baumannii from hospitalized patients in the United States, 1998 to 2001. Antimicrob. Agents Chemother.47:1681-1688.
Karlowsky, J. A., M. E. Jones, C. Thornsberry, A. T. Evangelista, Y. C. Yee, and D. F. Sahm.2005. Stable antimicrobial susceptibility rates for clinical isolates of Pseudomonas aeruginosa from the 2001-2003 tracking resistance in the United States today surveillance studies. Clin. Infect. Dis.40(Suppl. 2):S89-S98.
Kaye, K. S., A. D. Harris, M. Samore, and Y. Carmeli.2005. The case-case-control study design: addressing the limitations of risk factor studies for antimicrobial resistance. Infect. Control Hosp. Epidemiol.26:346-351.
Kim, B. N., J. H. Woo, M. N. Kim, J. Ryu, and Y. S. Kim.2002. Clinical implications of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae bacteraemia. J. Hosp. Infect.52:99-106.
Kwon, K. T., W. S. Oh, J. H. Song, H. H. Chang, S. I. Jung, S. W. Kim, S. Y. Ryu, S. T. Heo, D. S. Jung, J. Y. Rhee, S. Y. Shin, K. S. Ko, K. R. Peck, and N. Y. Lee.2007. Impact of imipenem resistance on mortality in patients with Acinetobacter bacteraemia. J. Antimicrob. Chemother.59:525-530.
Landman, D., S. Bratu, S. Kochar, M. Panwar, M. Trehan, M. Doymaz, and J. Quale.2007. Evolution of antimicrobial resistance among Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae in Brooklyn, N.Y. J. Antimicrob. Chemother.60:78-82.
Laupland, K. B., M. D. Parkins, D. L. Church, D. B. Gregson, T. J. Louie, J. M. Conly, S. Elsayed, and J. D. Pitout.2005. Population-based epidemiological study of infections caused by carbapenem-resistant Pseudomonas aeruginosa in the Calgary Health Region: importance of metallo-beta-lactamase (MBL)-producing strains. J. Infect. Dis.192:1606-1612.
Lautenbach, E., J. B. Patel, W. B. Bilker, P. H. Edelstein, and N. O. Fishman.2001. Extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae: risk factors for infection and impact of resistance on outcomes. Clin. Infect. Dis.32:1162-1171.
Leavitt, A., S. Navon-Venezia, I. Chmelnitsky, M. J. Schwaber, and Y. Carmeli.2007. Emergence of KPC-2 and KPC-3 in carbapenem-resistant Klebsiella pneumoniae in an Israeli hospital. Antimicrob. Agents Chemother.51:3026-3029.
Lee, S. Y., S. Kotapati, J. L. Kuti, C. H. Nightingale, and D. P. Nicolau.2006. Impact of extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella species on clinical outcomes and hospital costs: a matched cohort study. Infect. Control Hosp. Epidemiol.27:1226-1232.
Livermore, D. M.2005. Tigecycline: what is it, and where should it be used? J. Antimicrob. Chemother.56:611-614.
Livermore, D. M., and N. Woodford.2006. The beta-lactamase threat in Enterobacteriaceae, Pseudomonas and Acinetobacter. Trends Microbiol.14:413-420.
Melzer, M., and I. Petersen.2007. Mortality following bacteraemic infection caused by extended spectrum beta-lactamase (ESBL) producing E. coli compared to non-ESBL producing E. coli. J. Infect.55:254-259.
Morosini, M. I., M. Garcia-Castillo, T. M. Coque, A. Valverde, A. Novais, E. Loza, F. Baquero, and R. Canton.2006. Antibiotic coresistance in extended-spectrum-beta-lactamase-producing Enterobacteriaceae and in vitro activity of tigecycline. Antimicrob. Agents Chemother.50:2695-2699.
Murray, C. K., and D. R. Hospenthal.2005. Treatment of multidrug resistant Acinetobacter. Curr. Opin. Infect. Dis.18:502-506.
National Nosocomial Infections Surveillance System (NNIS).2004. National Nosocomial Infections Surveillance (NNIS) System Report, data summary from January 1992 through June 2004, issued October 2004. Am. J. Infect. Control32:470-485.
Navon-Venezia, S., R. Ben-Ami, and Y. Carmeli.2005. Update on Pseudomonas aeruginosa and Acinetobacter baumannii infections in the healthcare setting. Curr. Opin. Infect. Dis.18:306-313.
Navon-Venezia, S., I. Chmelnitsky, A. Leavitt, M. J. Schwaber, D. Schwartz, and Y. Carmeli.2006. Plasmid-mediated imipenem-hydrolyzing enzyme KPC-2 among multiple carbapenem-resistant Escherichia coli clones in Israel. Antimicrob. Agents Chemother.50:3098-3101.
Ortega, B., A. B. Groeneveld, and C. Schultsz.2004. Endemic multidrug-resistant Pseudomonas aeruginosa in critically ill patients. Infect. Control Hosp. Epidemiol.25:825-831.
Paterson, D. L.2006. Resistance in gram-negative bacteria: Enterobacteriaceae. Am. J. Med.119:S20-S28.
Paterson, D. L., and R. A. Bonomo.2005. Extended-spectrum beta-lactamases: a clinical update. Clin. Microbiol. Rev.18:657-686.
Paterson, D. L., and Y. Doi.2007. A step closer to extreme drug resistance (XDR) in gram-negative bacilli. Clin. Infect. Dis.45:1179-1181.
Paul, M., M. Weinberger, Y. Siegman-Igra, T. Lazarovitch, I. Ostfeld, I. Boldur, Z. Samra, H. Shula, Y. Carmeli, B. Rubinovitch, and S. Pitlik.2005. Acinetobacter baumannii: emergence and spread in Israeli hospitals 1997-2002. J. Hosp. Infect.60:256-260.
Peleg, A. Y., J. Adams, and D. L. Paterson.2007. Tigecycline efflux as a mechanism for nonsusceptibility in Acinetobacter baumannii. Antimicrob. Agents Chemother.51:2065-2069.
Peleg, A. Y., B. A. Potoski, R. Rea, J. Adams, J. Sethi, B. Capitano, S. Husain, E. J. Kwak, S. V. Bhat, and D. L. Paterson.2007. Acinetobacter baumannii bloodstream infection while receiving tigecycline: a cautionary report. J. Antimicrob. Chemother.59:128-131.
Pitout, J. D., P. Nordmann, K. B. Laupland, and L. Poirel.2005. Emergence of Enterobacteriaceae producing extended-spectrum beta-lactamases (ESBLs) in the community. J. Antimicrob. Chemother.56:52-59.
Playford, E. G., J. C. Craig, and J. R. Iredell.2007. Carbapenem-resistant Acinetobacter baumannii in intensive care unit patients: risk factors for acquisition, infection and their consequences. J. Hosp. Infect.65:204-211.
Raja, N. S., and N. N. Singh.2007. Antimicrobial susceptibility pattern of clinical isolates of Pseudomonas aeruginosa in a tertiary care hospital. J. Microbiol. Immunol. Infect.40:45-49.
Rossi, F., F. Baquero, P. R. Hsueh, D. L. Paterson, G. V. Bochicchio, T. A. Snyder, V. Satishchandran, K. McCarroll, M. J. DiNubile, and J. W. Chow.2006. In vitro susceptibilities of aerobic and facultatively anaerobic gram-negative bacilli isolated from patients with intra-abdominal infections worldwide: 2004 results from SMART (Study for Monitoring Antimicrobial Resistance Trends). J. Antimicrob. Chemother.58:205-210.
Rubinstein, E., and D. Vaughan.2005. Tigecycline: a novel glycylcycline. Drugs65:1317-1336.
Ruzin, A., M. A. Visalli, D. Keeney, and P. A. Bradford.2005. Influence of transcriptional activator RamA on expression of multidrug efflux pump AcrAB and tigecycline susceptibility in Klebsiella pneumoniae. Antimicrob. Agents Chemother.49:1017-1022.
Schito, G. C.2006. The importance of the development of antibiotic resistance in Staphylococcus aureus. Clin. Microbiol. Infect.12(Suppl. 1):3-8.
Schwaber, M. J., and Y. Carmeli.2007. Mortality and delay in effective therapy associated with extended-spectrum β-lactamase (ESBL)-production in Enterobacteriaceae bacteremia: a systematic review and meta-analysis. J. Antimicrob. Chemother.60:913-920.
Schwaber, M. J., S. Navon-Venezia, K. S. Kaye, R. Ben-Ami, D. Schwartz, and Y. Carmeli.2006. Clinical and economic impact of bacteremia with extended-spectrum-β-lactamase-producing Enterobacteriaceae. Antimicrob. Agents Chemother.50:1257-1262.
Schwaber, M. J., S. Navon-Venezia, D. Schwartz, and Y. Carmeli.2005. High levels of antimicrobial coresistance among extended-spectrum-β-lactamase-producing Enterobacteriaceae. Antimicrob. Agents Chemother.49:2137-2139.
Talbot, G. H., J. Bradley, J. E. Edwards, Jr., D. Gilbert, M. Scheld, and J. G. Bartlett.2006. Bad bugs need drugs: an update on the development pipeline from the Antimicrobial Availability Task Force of the Infectious Diseases Society of America. Clin. Infect. Dis.42:657-668.
Thomson, J. M., and R. A. Bonomo.2005. The threat of antibiotic resistance in gram-negative pathogenic bacteria: beta-lactams in peril! Curr. Opin. Microbiol.8:518-524.
Tofteland, S., B. Haldorsen, K. H. Dahl, G. S. Simonsen, M. Steinbakk, T. R. Walsh, and A. Sundsfjord.2007. Effects of phenotype and genotype on methods for detection of extended-spectrum-β-lactamase-producing clinical isolates of Escherichia coli and Klebsiella pneumoniae in Norway. J. Clin. Microbiol.45:199-205.
Tognim, M. C., S. S. Andrade, S. Silbert, A. C. Gales, R. N. Jones, and H. S. Sader.2004. Resistance trends of Acinetobacter spp. in Latin America and characterization of international dissemination of multi-drug resistant strains: five-year report of the SENTRY Antimicrobial Surveillance Program. Int. J. Infect. Dis.8:284-291.
Tsuji, A., I. Kobayashi, T. Oguri, M. Inoue, E. Yabuuchi, and S. Goto.2005. An epidemiological study of the susceptibility and frequency of multiple-drug-resistant strains of Pseudomonas aeruginosa isolated at medical institutes nationwide in Japan. J. Infect. Chemother.11:64-70.
Tumbarello, M., M. Sanguinetti, E. Montuori, E. M. Trecarichi, B. Posteraro, B. Fiori, R. Citton, T. D'Inzeo, G. Fadda, R. Cauda, and T. Spanu.2007. Predictors of mortality in patients with bloodstream infections caused by extended-spectrum-β-lactamase-producing Enterobacteriaceae: importance of inadequate initial antimicrobial treatment. Antimicrob. Agents Chemother.51:1987-1994.
Tumbarello, M., T. Spanu, M. Sanguinetti, R. Citton, E. Montuori, F. Leone, G. Fadda, and R. Cauda.2006. Bloodstream infections caused by extended-spectrum-β-lactamase-producing Klebsiella pneumoniae: risk factors, molecular epidemiology, and clinical outcome. Antimicrob. Agents Chemother.50:498-504.
Turner, P. J., and J. M. Greenhalgh.2003. The activity of meropenem and comparators against Acinetobacter strains isolated from European hospitals, 1997-2000. Clin. Microbiol. Infect.9:563-567.
Unal, S., and J. A. Garcia-Rodriguez.2005. Activity of meropenem and comparators against Pseudomonas aeruginosa and Acinetobacter spp. isolated in the MYSTIC Program, 2002-2004. Diagn. Microbiol. Infect. Dis.53:265-271.
Villegas, M. V., K. Lolans, A. Correa, C. J. Suarez, J. A. Lopez, M. Vallejo, and J. P. Quinn.2006. First detection of the plasmid-mediated class A carbapenemase KPC-2 in clinical isolates of Klebsiella pneumoniae from South America. Antimicrob. Agents Chemother.50:2880-2882.
Walsh, T. R., M. A. Toleman, L. Poirel, and P. Nordmann.2005. Metallo-beta-lactamases: the quiet before the storm? Clin. Microbiol. Rev.18:306-325.
Wilson, S. J., C. J. Knipe, M. J. Zieger, K. M. Gabehart, J. E. Goodman, H. M. Volk, and R. Sood.2004. Direct costs of multidrug-resistant Acinetobacter baumannii in the burn unit of a public teaching hospital. Am. J. Infect. Control32:342-344.
Wong, T. H., B. H. Tan, M. L. Ling, and C. Song.2002. Multi-resistant Acinetobacter baumannii on a burns unit—clinical risk factors and prognosis. Burns28:349-357.
Yip, T., K. C. Tse, M. F. Lam, S. Tang, F. K. Li, B. Y. Choy, S. L. Lui, T. M. Chan, K. N. Lai, and W. K. Lo.2006. Risk factors and outcomes of extended-spectrum beta-lactamase-producing E. coli peritonitis in CAPD patients. Perit. Dial. Int.26:191-197.
Zaoutis, T. E., M. Goyal, J. H. Chu, S. E. Coffin, L. M. Bell, I. Nachamkin, K. L. McGowan, W. B. Bilker, and E. Lautenbach.2005. Risk factors for and outcomes of bloodstream infection caused by extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella species in children. Pediatrics115:942-949.
Zavascki, A. P., A. L. Barth, A. L. Goncalves, A. L. Moro, J. F. Fernandes, A. F. Martins, F. Ramos, and L. Z. Goldani.2006. The influence of metallo-beta-lactamase production on mortality in nosocomial Pseudomonas aeruginosa infections. J. Antimicrob. Chemother.58:387-392.

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Antimicrobial Agents and Chemotherapy
Volume 52Number 3March 2008
Pages: 813 - 821
PubMed: 18070961


Published online: 17 December 2020


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Christian G. Giske [email protected]
Clinical Microbiology L2:02, Karolinska Institutet-MTC, Karolinska University Hospital Solna, SE-17176 Stockholm, Sweden
Dominique L. Monnet
National Center for Antimicrobials and Infection Control, Statens SerumInstitut, Copenhagen, Denmark
Present address: Scientific Unit, European Centre for Disease Prevention and Control, Stockholm, Sweden.
Otto Cars
Antibiotic Research Unit, Department of Medical Sciences, Clinical Bacteriology and Infectious Diseases, Uppsala University, Uppsala, Sweden
Yehuda Carmeli
Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Boston, Massachusetts
Division of Epidemiology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
on behalf of ReAct-Action on Antibiotic Resistance

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