An update on newer [beta]-lactamases.
|Publication:||Name: Indian Journal of Medical Research Publisher: Indian Council of Medical Research Audience: Academic Format: Magazine/Journal Subject: Biological sciences; Health Copyright: COPYRIGHT 2007 Indian Council of Medical Research ISSN: 0971-5916|
|Issue:||Date: Nov, 2007 Source Volume: 126 Source Issue: 5|
|Topic:||Event Code: 310 Science & research|
|Product:||Product Code: 8000200 Medical Research; 9105220 Health Research Programs; 8000240 Epilepsy & Muscle Disease R&D NAICS Code: 54171 Research and Development in the Physical, Engineering, and Life Sciences; 92312 Administration of Public Health Programs SIC Code: 8730 Research and Testing Services|
|Geographic:||Geographic Scope: India Geographic Code: 9INDI India|
The resistance to [beta]-lactam antibiotics is an increasing
problem worldwide and [beta] lactamases production is the most common
mechanism of drug resistance. Both global and Indian figures showed a
marked increase in the number of [beta]-lactamases producing organisms.
These enzymes extended spectrum [beta]-lactamases (ESBLs) are numerous
and continuous mutation has led to the development of enzymes having
expanded substrate profile. To date, there are more than 130 TEM type
and more than 50 sulphydryl variable (SHV) type [beta]-lactamases found
in Gram negative bacilli. ESBL producing Enterobacteriaceae are, as a
rule, resistant to all cephalosporins and extended spectrum penicillins
including the monobactam, aztreonam, while resistance to
trimethoprim--sulphamethaxazole and aminoglycosides is frequently
co-transferred on the same plasmid. Many ESBL producing organisms also
express Amp C [beta]-lactamases. Amp C-[beta]-lactamases are clinically
significant, as these confer resistance to cephalosporins in the
oxyimino group, 7[alpha]-methoxy cephalosporins, and are poorly
inhibited by clavulanic acid. Carbepenems are the drugs of choice for
the treatment of infections caused by ESBL producing organisms but
carbapenemases (MBLs) have emerged and have spread from Pseudomonas
aeruginosa to Enterobacteriaceae. The routine clinical microbiology
laboratories should employ simple methods to recognize these enzymes
using various substrates and inhibitors. These organisms may lead to
therapeutic dead ends. Presently, the therapy relies on [beta]-lactam/
[beta]-lactamases inhibitor combinations, carbepenems and
piperacillin--tazobactam plus aminoglycoside combination. Proper
infection control practices and barrier precautions are essential to
contain the organisms producing [beta]-lactamases.
Key words [beta]-lactamases--ESBL--MBL--resistance--SHV--TEM
The first [beta]-lactamase was identified in Escherichia coli prior to the release of penicillin for use in medical practice (1). In Gram negative pathogens, [beta]-lactamase production remains the most important contributing factor to [beta]-lactam resistance (2).
The four major groups of [beta]-lactams penicillin, cephalosporins, monobactams and carbapenems have a 13-1actam ring which can be hydrolysed by [beta]-lactamases resulting in microbiologically ineffective compounds (3). The persistent exposure of bacterial strains to a multitude of [beta]-lactams has led to overproduction and mutation of [beta]-lactamases. These [beta]-lactamases are now capable of hydrolyzing penicillins, broad-spectrum cephalosporins and monobactams. Thus these are new [beta]-lactamases and are called as extended spectrum beta lactamases (ESBLs) (4). In Gram negative bacteria these enzymes remain in the periplasmic space, where they attack the antibiotic before it can reach its receptor site (5). The first plasmid mediated [beta]-lactamase was described in early 1960 (6). ESBLs have been isolated from a wide variety of Enterobacteriaceae, Pseudomonas aeruginosa and Capnocytophaga ochracea (7-9).
On the basis of mechanism of action, most common [beta]-lactamases are divided into three major classes (A,C & D) depending on amino acid sequences. These enzymes act on many penicillins, cephalosporins and monobactams. Class B [beta]-lactamases called as metallo beta lactamases (MBLs), act on penicillins, cephalosporins and carbapenems but not on monobactams (10). MBLs differ from other [beta]-lactamases in using metal ion zinc, linked to a histidine or cysteine residue to react with the carbonyl group of the amide bond of most penicillins, cephalosporins and carbapenems (11). Another class, Amp C-[beta]-lactamases are also clinically significant, since they confer resistance to cephalosporins in the oxyimino group, 7[alpha]-methoxy cephalosporins and are not affected by available [beta]-lactamase inhibitors (12). Amp C [beta]-lactamases have been reported in E. coli, Klebsiella pneumoniae, Salmonella spp., Citrobacter freundii, Enterobacter aerogenes and Proteus mirabilis (13-15).
Origin & spread
Many Gram negative bacteria possess a naturally occurring, chromosomally mediated [beta]-lactamase. These enzymes may have evolved from penicillin binding proteins with which they show some sequence homology. This development was likely due to selective pressure exerted by [beta]-lactam producing soil organisms found in the environment (16). The TEM 1 enzyme was originally found in E. coli isolated from a patient named Temoniera hence named as TEM (17). Being plasmid and transposon mediated has facilitated the spread of TEM 1 to other species of bacteria. The second common plasmid mediated [beta]-lactamase found in K. pneumoniae and E. coli is SHV 1 (sulphydryl variable). The SHV1 [beta]-lactamase is chromosomally encoded in the majority of isolates of K. pneumoniae but is usually plasmid mediated in E. coli (18). The first real ESBL to be described in 1983 was TEM 3, and now over 100 additional TEMs have been isolated (7). Unlike the TEM type [beta]-lactamases, there are fewer derivatives of SHV 1. However, a multi-resistant transferable plasmid encoding the SHV 5 [beta]-lactamase causing unusually high resistance to ceftazidime and aztreonam and combination of acetylating enzymes producing resistance to all clinically available aminoglycosides was identified in K. pneumoniae (19). K. pneumoniae has been considered as the main agent producing ESBL. This may be attributed to presence of large mult-iresistant plasmids and presence of ESBL genes on these plasmids. Also Klebsiella is more adapted to hospital environment and longer survival of this organism on hands, environmental surfaces facilitates cross infection within hospitals (20).
An individual acquires an ESBL strain either due to contact with the colonized health care worker or contaminated fomites. After this, the isolate emerges as a result of selective effect of antibiotic use (21). Removal of selective pressure by drug class restriction leads to the disappearance of ESBL producing strains (22). Some important factors related to acquisition and infection with ESBL producing organisms are seriously ill patients with prolonged hospital stays, in whom invasive medical devices are present (23-25). Heavy antibiotic use is also a risk factor for acquisition of an ESBL producing organism (26). Use of many third generation cephalosporins, ceftazidime, quinolones, and aminoglycosides has been shown to be associated with emergence of ESBLs (27-30). Patient to patient transmission has also been described (23). However, same ESBLs in a particular unit of a hospital may be mediated by different plasmids and many different ESBLs may be found in the same unit at a same time (31). Intensive care units are usually the epicenters of ESBLs production. Transfer of genotypically related ESBLs may occur from hospital to hospital (32), from city to city (33), country to country (34) and even intercontinental transfer has been described (35). Community acquired infection with ESBLs have also been found (36).
[beta]-lactamases are increasing in number and diversification of the group of enzymes is occurring that inactivates [beta]-lactam type of antibacterials. These can be classified based on two major approaches. One is based on the biochemical and functional characteristics of the enzymes and the second is based on the molecular structure of the enzyme.
Functional classification of the [beta]-lactamases is based on spectrum of antimicrobial substrate profile, enzyme inhibition profile, enzyme net charge, hydrolysis rate and other parameters. Bush et al (37) presented the classification based on 4 major groups (1-4) and subgroups (a-f)37. According to this classification, most ESBLs belong to group 2 B e, which is [beta]-lactamases inhibited by clavulanic acid, which can hydrolyze penicillins, narrow and extended spectrum cephalosporins and monobactams.
Characterization and types of ESBLs
Classical ESBLs have evolved from the widespread plasmid-encoded enzymes families TEM, SHV, cefotaxime (CTX-M) and oxacillin (OXA).
TEM (Class A): TEM 1 is capable of hydrolyzing penicillins and first generation cephalosporins but is unable to attack the oxyimino cephalosporin. The first TEM variant with increased activity against extended spectrum cephalosporins was TEM 3 (38,39). To date, there are > 130 TEM type and > 50 SHV type [beta]-lactamases, and it appears that new ones are being found every week. They are mainly found in E.coli, K.pneumoniae and P. mirabilis (7) but can occur in other members of the Enterobacteriaceae family and in some non-enteric organisms such as Acinetobacter species.
SHV (Class A): The progenitor of the SHV class of enzymes, SHV-1, is universally found in K. pneumoniae. SHV 1 confers resistance to broad spectrum penicillins such as ampicillin, ticarcillin and piperacillin but not to oxyimino substituted cephalosporins (14). In 1983, a new SHV derived from a mutation in SHV 1 which is called plasmidic SHV 2, was isolated from three isolates of K. pneumoniae which demonstrated, transferable resistance to cefotaxime as well as to other newer cephalosporins (40). To date, more than 50 SHV type [beta]-lactamases have been described (7).
CTX-M (Class A): A new family of [beta]-lactamases that preferentially hydrolyzes cefotaxime has arisen. It has been found in isolates of Salmonella enterica serovar. Typhimurium and E. coli mainly and some other species of Enterobacteriaceae (40-41). These are not very closely related to TEM or SHV [beta]-lactamases (43). In addition to the rapid hydrolysis of cefotaxime, another unique feature of these enzymes is that they are better inhibited by the [beta]-lactamase inhibitor tazobactam than by sulbactam and clavulanate (44,45).
Recently CTX-M enzymes have been recognized in a number of focal outbreaks from many parts of the world, e.g. in Japan (Toho-2)45, India (CTX-M-15) (46) and UK (47) suggesting their wide dispersal.
OXA (Class D): The OXA type oxacillin hydrolyzing enzymes are another family of [beta]-lactamases and have been found mainly in P. aeruginosa (47). OXA [beta]-lactamases belong to Ambler class D (48). These enzymes confer resistance to ampicillin and cephalothin and are characterized by their high hydrolytic activity against oxacillin and cloxacillin and are poorly inhibited by clavulanic acid (37). Many of the newer members of the OXA [beta]-lactamase family have been found in bacterial isolates originating in Turkey and in France.
Other unusual enzymes having ESBL have also been described (e.g., BES-1, CME-1, VE-B-1, PER, SFO-1, GES-1) (7). These novel enzymes are found infrequently.
The spread of [beta]-lactamases may be chromosomal or plasmid mediated. The genes encoding some [beta]-lactamases are carried by transposons (49). Many genes may be found in integrons. Sometimes, [beta]-lactamase resistance markers are a part of the integron that has gene cassettes encoding resistance genes for other classes of antibiotics as well (50). Decreased porin production and overproduction of [beta]-lactamases can also result in enhanced resistance, e.g. in K. pneumoniae K 6 strain there is novel ESBL--SHV 18 and it also exhibits the loss of two outer membrane porins (51). In this case although the enzyme hydrolyzed cephotaxime more than the ceftazidime but K6 strain was more resistant to ceftazidime because of possible increased penetration of cefotaxime or increased efflux of ceftazidime (52). This combination of mechanisms for resistance have been described in group 1 cephalosporinases as well (53).
The gene for TEM 1 and TEM 2 are carried by transposons (54). The gene encoding SHV 1 is found on the chromosome of most isolates of K. pneumoniae (55,56). SHV genes may also occur on transmissible plasmids (57).
Genes for the remaining new types of [beta]-lactamases are usually found incorporated into integrons. Integrons are involved in the acquisition of AmpC type [beta]-lactamases by plasmids (58). Carbapenemases of the Imimenem (IMP) and Verona integrons encoded (VIM) families are also found within integrons. Conjugational transfer of wide host range R--plasmids bearing [bla.sub.IMP] gene is the mechanism of dissemination of [bla.sub.IMP] gene cassettes onto various Gram negative bacterial species (59). Another mode of resistance is that impenem and meropenem resistant mutants of Enterobacter cloacae and Proteus rettgeri lack porins (60).
Due to difficulties in detecting ESBL producers and inconsistencies in reporting it is difficult to determine the true prevalence of ESBL producing organisms. However, the ESBL producing organisms are distributed worldwide and their prevalence is increasing. The incidence of ESBL varies depending on the area of the world the isolates belong to. The first ESBL producing organism was detected in Europe. Although, the initial reports were from Germany and England (40,61), later on many reports came from France (39,62). The proliferation of ESBLs in France was quite dramatic. Up to 35 per cent of hospital acquired K. pneumoniae were found to be ESBL producers by early 1990s (63). Strict infection control interventions led to the decline in the incidence of ESBL producers. However, ESBL producing K. pneumoniae are rising in Eastern Europe, in addition 30.2 per cent of Enterobacter are showing ESBL production (64). In USA, the first report occurred in 1988 (65). National Nosocomial Infections Surveillance (NNIS) figures revealed 6.1 per cent of K. pneumoniae isolates from ICU while only 1.8 per cent of outpatient isolates of K. pneumoniae to be ESBL producers (66). CTX-M type ESBL has recently been described in USA and Canada (67-69). Various ESBL types reported from South America are SHV 2, SHV 5, CTX-M 2, GES-1 and BES 170-73. As high as 32 to 60 per cent of Klebsiellae isolates from ICU in Brazil, Columbia and Venezuela have been found to be ESBL producers (74-77). From Africa and Middle East, the ESBL production has been reported in 6.1 per cent of K. pneumoniae isolates in a single South African Hospital (78). CTX-M-12 has been found in Kenya (79). TEM and SHV types of ESBLs have been characterized from South Africa (80,81). GES-2 has also been reported from P. aeruginosa (82). In Australian hospitals the proportion of ESBL GES-2 producing K. pneumoniae isolates was about 5 per cent (76). From China, the figures of ESBL producers varies between 25-40 per cent (83). SHV-2 has also been found in China (84). About 12-24 per cent of isolates from Thailand, Taiwan, Philippines and Indonesia have been described by national surveys to be ESBL producers (7). In Japan, 5 per cent of K. pneumoniae are ESBL producers (85). The various lineage of SHV viz., SHV 2, SHV 5, SHV 12 and others have been described from Japan (86). Recently, CTX-M types have been reported from China, Japan, Korea and Taiwan (87-90). The SENTRY Surveillance Program covered the period 1997-1999 and MYSTIC covered 1997-2003 (91) also the latter included a greater number of Intensive Care Units, the figure of MYSTIC program showed an overall increase over SENTRY Surveillance Program (92). Apart from K. pneumoniae, E. coli, K. oxytoca, ESBLs have become common in P. mirabilis. ESBLs in Salmonella spp. are also growing (93).
A latest study from US reported 4.9 per cent of all Enterobacteriacae to be ESBL producers. These isolates occurred at 74 per cent of the ICU and 43 per cent of the non ICU sites. Transferable Amp C beta lactamases were detected in 3.3 per cent of K. pneumoniae isolates (94).
Carbapenem resistant Serratia marcescens and P. aeruginosa emerged in Japan nearly l0 years ago (95,96). These strains produced IMP 1 which is plasmid mediated. Strains carrying bla (IMP-l) with a class 1 integron are the most prevalent types in Japan (97). However, now these have also been identified in Europe and Singapore (98,99).
In the last 4-5 yr, new transferable MBLs have spread rapidly. In some countries, P. aeruginosa possessing MBLs constitute nearly 20 per cent of all nosocomial isolates, whereas in other countries the number is comparatively low (100,101). The spread of MBL genes is likely to rise further highlights the importance of reporting and studying the epidemic spread of these enzymes by various surveillance projects like SENTRY, MYSTIC, Alexander and EARSS (102).
Many bacterial species like Enterobacter, S. marcescens, E. coli, P. aeruginosa and C. freundii possess [beta]-lactamases of the Amp C type (103). The product of Amp C gene is an enzyme that is broadly active against cephalosporins but is not inhibited by clavulanate. This differentiated Amp C enzymes from ESBLs. Further, migration of chromosomal Amp C genes into plasmids poses a serious threat. Usually, the plasmid encoded Amp C [beta]-lactamases are present in species that do not possess a chromosome encoded version of the enzymes (104). CTX-M types of ESBLs are regarded as emerging pathogens. A recent study from Spain showed 70 per cent of the ESBL producing E. coli from bacteraemia cases to be of CTX-M types (105).
In India, ESBL producing strains of Enterobacteriaceae have emerged as a challenge in hospitalized as well as community based patients. In 1997, from Nagpur 17 out of 66 Klebsiella isolates showed ESBL production (106). In 2002, 68 per cent of Gram negative bacteria were found to be ESBL producers in a study from New Delhi in which 80 per cent of Klebsiella were ESBL (107). In 2004 two other studies from Delhi showed 70.6 and 12.6 per cent Klebsiella isolates to be ESBL producers respectively (108,109). Another comparatively recent study in 2005 from New Delhi, showed 68.78 per cent of the strains of Gram negative bacteria to be ESBL producers (110). ESBLs have been reported from community isolates from north India as well (111). A study from Coimbatore, Tamil Nadu, showed the presence of ESBL to be 40 per cent while from Nagpur this figure was 50 per cent in urinary isolates (112,113). In a study from Chennai, ESBL production was detected in 6 out of 90 isolates of K. pneumoniae in children under five with intestinal infections (114). Further a study from Karnataka showed the frequency of ESBLs in neonatal septicaemic cases to be 22.7 per cent (115). A similar study from Lucknow showed high levels of ESBL production (63.6-86.6 %) (116). Amp C enzyme has also been described in 3.3 per cent of isolates from Karnataka (117). Metallo-beta-lactamase production is a significant problem especially in hospital isolates of P. aeruginosa and Acinetobacter species. Reports have described the prevalence of MBLs in P. aeruginosa (118,119) and Acinetobacters species as well from India (120).
The results of the initial studies for the MYSTIC programme in India confirmed the high levels of resistance and ESBL production in Gram-negative bacilli including Salmonella (121). The latest report from National Institute of Communicable Diseases (NICD), New Delhi, India, shows PCR as a reliable method for detection of ESBLs as well as the rise of resistance to cefepime--a fourth generation cephalosporin (122). CTX-M-15 has also been found in Indian E. coli and K. pneumoniae strains (123).
Methods of detection
Different ESBL enzymes depict variable levels of resistance to third generation cephalosporins. According to National Committee for Clinical Laboratory Standards (NCCLS) now Clinical and Laboratory Standards (CLSI) interpretive definitions, ESBLs do not always increase MICs to levels characterized as resistant (124,125) Now, it is mandatory that the routine clinical microbiology laboratory employs ESBL detection methods which are sensitive enough to recognize the level of resistance that would be achieved by the situation given in vivo.
Screening tests: Initial screening for reduced susceptibility to cefpodoxime, cefotaxime, ceftriaxone, ceftazidime or aztreonam and then performing phenotypic confirmatory test is recommended. As proposed by the CLSI, M100-S-16 document, the use of more than one of the five indicator cephalosporins suggested will improve the sensitivity of detection (126). But, if it is necessary to rely on a single screening substance, ceftazidime or cefpodoxime would be the best choice (127).
Confirmatory tests (127): (i) The double disk approximation test: A susceptibility disk containing amoxicillin-clavulanate and a disk containing one of the oximino [beta]-lactam antibiotics is used. Enhancement of the zone of ceftazidime disk on the side facing the amoxicillin-clavulanate disk is interpreted as a positive test (129). (ii) Combined disk method--Commercialized disks containing clavulanate plus ceftazidime or cefotaxime (10 [micro]g plus 30 [micro]g respectively) are used in this method (130). (iii) E test ESBL strip--In this method the zone of inhibition is read from two halves of the strip. A decrease in the MIC of ceftazidime of more than three dilutions in the presence of clavulanate is interpreted as a positive test. Sometime due to weak enzyme production, indeterminate results may be obtained. (iv) Three dimensional test--This method is very sensitive, but is technically difficult and labour-intensive requiring experienced clinical microbiologist to interpret the result (131). (v) The automated ESBL microbial susceptibility test system--This method utilizes either ceftazidime or cefotaxime alone and in combination with clavulanic acid (4 [micro]g/ml). A predetermined reduction in growth in wells containing clavulanate compared with those containing each single drug indicates the presence of an ESBL. Vitek ESBL test system has shown variable results (132) (vi) Recently CLSI has recommended initial screening by testing for growth in a broth medium containing 1 [micro]g/ml of one of five extended spectrum [beta]-lactam antibiotics (128). For identification of specific ESBL expressed in a clinical isolate, the following molecular detection methods can be applied: Specific DNA probes, PCR with oligonucleotide primers oligotyping, PCR followed by restriction fragment length polymorphism analysis, ligase chain reaction and nucleotide sequencing. These techniques are available only in research centres and are beyond the scope of routine clinical microbiology laboratories.
Regarding the reporting of ESBL producing isolates, the microbiology laboratory report should state that the strain produced ESBL and should be considered resistant to all penicillins, cephalosporins and aztreonam.
For clinical laboratories to adapt a method for screening for metallo beta-lactamases, the suggested methodology is as follows; firstly, the isolates are targeted based on ceftazidime and carbapenem MIC, e.g. P. aeruginosa with an imipenem MIC> 16 [micro]g/ml and Acinetobacter spp. isolates with an MIC >2 [micro]g/ml is appropriate. For ease of application, the E test MBL strip is recommended (133). To increase the sensitivity of MBL detection, several substrates (imipenem, ceftazidime and meropenem) should be used preferably with more than one inhibitor (EDTA and mercaptopropionic acid) (134). It should be of help if clinical laboratories are able to detect organisms producing plasmid mediated Amp-C [beta]-lactamases with a method, which is simple as well as inexpensive. CLSI has no recommendations available for detection of these organisms. A number of reports have been published based on different methodologies used (135-137).
ESBL producing members of Enterobacteriaceae are, as a rule, resistant to all cephalosporins and extended spectrum penicillins, including the monobactam, aztreonam, while resistance to trimethoprim-sulfamethoxazole and aminoglycosides is frequently co-transferred on the same plasmid (138). Third and fourth generation cephalosporins should not be used even in the presence of apparent susceptibility. Cephamycins such as cefoxitin, cefotetan and moxalactam may be used for ESBL producing E.coli and Klebsiella spp. However, cephamycin therapy leads to emergence of plasmid mediated Amp C resistance. These enzymes are phylogenetically very distinct from the ESBL families and confer resistance to third generation cephalosporins as well as cephamycins (139,140). ESBLs are usually susceptible to [beta]-lactam / [beta]-lactamase inhibitor combinations, but these drugs can usually be overwhelmed by particularly large amounts of enzyme and thus show in vivo resistance. Treatment with [beta]-lactam/ [beta]-lactamase inhibitor combination was shown to be inferior to treatment with imipenem or piperacillin/ tazobactam plus aminoglycoside combination in an animal model (140). Currently the carbapenems, are regarded as the drugs of choice against ESBL producing organisms (7). Carbapenem treatment however, is not without its own complication because MBL producers which are carbapenem resistant, have already spread in various parts of the world (98,99). The only therapeutic option available for MBL producers is polymyxin (141). These molecules should not be used as monotherapy but may be combined with some aminoglycoside molecule. Also rifampin may be an interesting agent for treating multi-drug resistant P. aeruginosa infections. Thus, there is a need for developing novel agents in the near future otherwise these organisms may lead to therapeutic dead ends.
Proper infection control practices and barriers are essential to prevent spread and outbreaks of ESBL producing bacteria. The reservoir for these bacteria seems to be gastrointestinal tract (142), oropharynx, colonized wounds and urine.
The colonized hands, equipment could help in spreading infection between patients. So, mandatory infection control practices would be hand washing, barrier precautions, isolation of colonized/infected patients. Surveillance of patients of ICUs will help in early detection and control practices related to ESBL production. Antibiotic restriction and antibiotic cycling especially the empirical use of higher generation cephalosporins and carbepenems are other measures which if monitored properly, could help in control of the emergence and spread of ESBL producing bacteria.
The incidence of infections due to organisms resistant to [beta]-lactam agents due to production of various enzymes has increased in recent years. Detection of ESBL production is of paramount importance both in hospital and community isolates. Firstly, these strains are probably more prevalent than currently recognized. Secondly, ESBLs constitute a serious threat to currently available antibiotics. Thirdly, institutional outbreaks are increasing because of selective pressure due to heavy use of expanded spectrum cephalosporins and lapses in effective control measures. So vigilance and timely recognition of infection with resistant bacteria and appropriate antibiotic therapy, is the only answer to the current multi drug resistant bacterial population. Careful attention to barrier precautions and hand hygiene can help in preventing the spread of these, multi drug resistant Gram-negative microorganisms.
Received July 11, 2006
(1.) Abraham EP, Chain E. An enzyme from bacteria able to destroy penicillin. Nature 1940; 146 : 837.
(2.) Medeiros AA. Evolution and dissemination of [beta]-lactamases accelerated by generations of [beta]-lactam antibiotics. Clin Infect Dis 1997; 24 : S19-45.
(3.) Bush K, Mobashery S. How [beta]-lactamases have driven pharmaceutical drug discovery: from mechanistic knowledge to clinical intervention. In: Rosen B, Rosen SM, editors. Resolving the antibiotic paradox. New York: Plenum Publishers; 1998. p. 71-98.
(4.) Bush K. New beta-lactamases in Gram-negative bacteria: diversity and impact on the selection of antimicrobial therapy. Clin Infect Dis 2001; 32 : 1085-9.
(5.) Stratton CW. Mechanisms of bacterial resistance to antimicrobial agents. Lab Med 2000; 48 : 186-98.
(6.) Datta N, Kontomichalou P. Penicillinase synthesis controlled by infectious R Factors in Enterobacteriaceae. Nature 1965; 208 : 239-44.
(7.) Bradford PA. Extended spectrum beta lactamases in the 21st century: characterization, epidemiology and detection of this important resistance threat. Clin Microbiol Rev 2001; 14 : 933-51.
(8.) Naas T, Philippon L, Poirel L, Ronco E, Nordmann P. An SHV derived expanded-spectrum beta-lactamase in Pseudomonas aeruginosa. Antimicrob Agents Chemother 1999; 43 : 1281-4.
(9.) Rosenau A, Cattier B, Gousset N, Harrian P, Phillippon A, Quentin R, et al. Capnocytophaga ochracea: characterization of a plasmid encoded expanded-spectrum TEM-17 beta-lactamase in the phylum Flavobacter-Bacteroides. Antimicrobial Agents Chemother 2000; 44 : 760-2.
(10.) Ambler RP. The structure of [beta]-lactamases. Philos Trans R Soc Lond B Biol Sci 1980; 289 : 321-31.
(11.) Walsh TR, Mark AT, Laurent P, Patrice N. Metallo-beta-lactamases: the quiet before the storm? Clin Microbiol Rev 2005; 18 : 306-25.
(12.) Thomson KS. Controversies about extended-spectrum and AmpC beta-lactamases. Emerg Infect Dis 2001; 7 : 333-6.
(13.) Bauernfeind A, Chong Y, Lee K. Plasmid-encoded AmpC beta-lactamases: How far have we gone 10 years after the discovery? Yonsei Med J 1998; 39 : 520-5.
(14.) Livermore DM. [beta]-lactamases in laboratory and clinical resistance. Clin Microbiol Rev 1995; 8 : 557-84.
(15.) Phillippon A, Arlet G, Lagrange PH. Origin and impact of plasmid-mediated extended-spectrum [beta]-lactamases. Eur J Clin Microbiol Infect Dis 1994; 13 (Suppl. 1) : S17-29.
(16.) Ghuysen JM. Serine [beta]-lactamases and penicillin-binding proteins. Annu Rev Microbiol 1991; 45 : 37-67.
(17.) Medeiros AA. [beta]-Lactamases. Br Med Bull 1984; 40 : 18-27.
(18.) Tzouvelekis LS, Bonomo RA. SHV-type beta-lactamases. Curr Pharm Des 1999; 5 : 847-64.
(19.) Galani I, Xirochauki E, Kanallakopoulou K, Petrikoss G, Giamarellou H. Transferable plasmid mediating resistance to multiple antimicrobial agents in Klebsiella pneumoniae isolates in Greece. Clin Microbiol Infect 2002; 8 : 579-88.
(20.) Casewell MW, Phillips I. Aspects of the plasmid-mediated antibiotic resistance and epidemiology of Klebsiella species. Am J Med 1981; 70 : 459-62.
(21.) Lautenbach E, Strom BL, Bilker WB, Patel JB, Edelstein PH, Fishman NO. Extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae: risk factors for infection and impact of resistance on outcomes. Clin Infect Dis 2001; 32 : 1162-71.
(22.) Urban C, Mariano N, Rahman N, Queenan AN, Montenegro D, Bush K, et al. Detection of multiresistant ceftazidime-susceptible Klebsiella pneumoniae isolates lacking TEM-26 after class restriction of cephalosporins. Microb Drug Resist 2000; 6 : 297-303.
(23.) Paterson DL, Bonomo RA. Extended-spectrum beta-lactamases: a clinical update. Clin Microbiol Rev 2005; 18 : 657-86.
(24.) De Champs C, Sauvant MP, Chanal C, Sirot D, Gazuy N, Malhuret R, et al. Prospective survey of colonization and infection caused by expanded-spectrum-beta-lactamase-producing members of the family Enterobacteriaceae in an intensive care unit. J Clin Microbiol 1989; 27 : 2887-90.
(25.) Wiener J, Quinn JP, Bradford PA, Goering RV, Nathan C, Bush K, et al. Multiple antibiotic-resistant Klebsiella and Escherichia coli in nursing homes. JAMA 1999; 281 : 517-23.
(26.) Pena C, Pujol M, Ardanuy C, Ricart A, Pallares R, Linares J, et al. Epidemiology and successful control of a large outbreak due to Klebsiella pneumoniae producing extended-spectrum beta-lactamases. Antimicrob Agents Chemother 1998; 42 : 53-8.
(27.) Lee SH, Kim JY, Shin SH, An YJ, Choi YW, Jung YC, et al. Dissemination of SHV-12 and characterization of new AmpC-type beta-lactamase genes among clinical isolates of Enterobacter species in Korea. J Clin Microbiol 2003; 41 : 2477-82.
(28.) Rice LB, Eckstein EC, DeVente J, Shlaes DM. Ceftazidime-resistant Klebsiella pneumoniae isolates recovered at the Cleveland Department of Veterans Affairs Medical Center. Clin Infect Dis 1996; 23: 118-24.
(29.) De Champs C, Rouby D, Guelon D, Sirot J, Sirot D, Beytout D, et al. A case-control study of an outbreak of infections caused by Klebsiella pneumoniae strains producing CTX-1 (TEM-3) beta-lactamase. J Hosp Infect 1991; 18 : 5-13.
(30.) Asensio A, Oliver A, Gonzalez-Diego P, Baquero F, Perez-Diaz JC, Ros P, et al. Outbreak of a multiresistant Klebsiella pneumoniae strain in an intensive care unit: antibiotic use as risk factor for colonization and infection. Clin Infect Dis 2000; 30 : 55-60.
(31.) Bradford PA, Cherubin CE, Idemyor V, Rasmussen BA, Bush K. Multiply resistant Klebsiella pneumoniae strains from two Chicago hospitals: identification of the extended-spectrum TEM-12 and TEM-10 ceftazidime-hydrolyzing beta-lactamases in a single isolate. Antimicrob Agents Chemother 1994; 38 : 761-6.
(32.) Monnet DL, Biddle JW, Edwards JR, Culver DH, Tolson JS, Martone WJ, et al. Evidence of interhospital transmission of extended-spectrum beta-lactam-resistant Klebsiella pneumoniae in the United States, 1986 to 1993. The National Nosocomial Infections Surveillance System. Infect Control Hosp Epidemiol 1997; 18 : 492-8.
(33.) Yuan M, Aucken H, Hall LM, Pitt TL, Livermore DM. Epidemiological typing of Klebsiellae with extended-spectrum beta-lactamases from European intensive care units. J Antimicrob Chemother 1998; 41 : 527-39.
(34.) Gori A, Espinasse F, Deplano A, Nonhoff C, Nicolas MH, Struelens MJ. Comparison of pulsed-field gel electrophoresis and randomly amplified DNA polymorphism analysis for typing extended-spectrum-beta-lactamase-producing Klebsiella pneumoniae. J Clin Microbiol 1996; 34 : 2448-53.
(35.) Shannon KP, King A, Phillips I, Nicolas MH, Philippon A. Importance of organisms producing broad-spectrum SHV-group beta-lactamases into the United Kingdom. J Antimicrob Chemother 1990; 25 : 343-51.
(36.) Rodriguez-Bano J, Navarro MD, Romero L, Martinez-Martinez L, Muniain MA, Perea EJ, et al. Epidemiology and clinical features of infections caused by extended-spectrum beta-lactamase-producing Escherichia coli in nonhospitalized patients. J Clin Microbiol 2004; 42 : 1089-94.
(37.) Bush K, Jacoby GA, Medeiros AA. A functional classification scheme for [beta]-lactamases and its correlation with molecular structure. Antimicrob Agents Chemother 1995; 39 : 1211-33.
(38.) Soughakoff W, Goussard S, Courvalin P. TEM-3 [beta]-lactamases which hydrolyzes broad-spectrum cephalosporins, is derived from the TEM-2 penicillinases by two amino acid substitutions. FEMS Microbiol Lett 1988; 56 : 343-48.
(39.) Sirot D, Sirot J, Labia R, Morand A, Courvalin P, Darfeuille-Michaud A, et al. Transferable resistance to third-generation cephalosporins in clinical isolates of Klebsiella pneumoniae: identification of CTX-1, a novel beta lactamase. J Antimicrob Chemother 1985; 28 : 302-7.
(40.) Knothe H, Shah P, Krcmery V, Antal M, Mitsuhashi S. Transferable resistance to cefotaxime, cefoxitin, cefamandole and cefuroxime in clinical isolates of Klebsiella pneumoniae and Serratia marcescens. Infection 1983; 11 : 315-7.
(41.) Gazouli M, Tzelepi E, Markogiannakis A, Legakis NJ, Tzouvelekis LS. Two novel plasmid-mediated cefotaxime-hydrolyzing [beta]-lactamases (CTX-M-5and CTX-M-6) from Salmonella typhimurium. FEMS Microbiol Lett 1998; 165 : 289-93.
(42.) Gazouli M, Tzelepi E, Sidorenko SV, Tzouvelekis LS. Sequence of the gene encoding a plasmid-mediated cefotaxime-hydrolyzing class A [beta]-lactamase (CTX-M-4): involvement of serine 237 in cephalosporin hydrolysis. Antimicrob Agents Chemother 1998; 42 : 1259-62.
(43.) Tzouvelekis LS, Tzelepi E, Tassios PT, Legakis NJ. CTX-M-type [beta]-lactamases: an emerging group of extended-spectrum enzymes. Int J Antimicrob Agents 2000; 14 : 137-43.
(44.) Bradford PA, Yang Y, Sahm D, Grope I, Gardovska D, Storch G. CTX-M-5, a novel cefotaxime-hydrolyzing [beta]-lactamase from an outbreak of Salmonella typhimurium in Latvia. Antimicrob Agents Chemother 1998; 42 : 1890-4.
(45.) Ma L, Ishii Y, Ishiguro M, Matsuzawa H, Yamaguchi K. Cloning and sequencing of the gene encoding Toho-2, a class A [beta]-lactamase preferentially inhibited by tazobactam. Antimicrob Agents Chemother 1998; 42 : 1181-6.
(46.) Karim A, Poirel L, Nagarajan S, Nordmann P. Plasmid mediated extended spectrum beta lactamase (CTX-M-3 like) from India and gene association with insertion sequence ISEcp1. FEMS Microbiol Lett 2001; 201 : 237-41.
(47.) Naas T, Nordmann P. OXA-type beta-lactamase. Curr Pharm Des 1999; 5 : 865-79.
(48.) Ambler RP, Coulson AF, Frere JM, Ghuysen JM, Joris B, Forsman M. A standard numbering scheme for the class A beta-lactamases. Biochem J 1991; 276 : 269-70.
(49.) Hedges RW, Jacob AE. Transposition of ampicillin resistance from RP4 to other replicons. Mol Gen Genet 1974; 132 : 31-40.
(50.) Poirel L, Naas T, Nicolas D, Collet L, Bellais S, Cavallo JD, et al. Characterization of VIM-2, a carbapenem-hydrolyzing metallo-beta-lactamase and its plasmid- and integron-borne gene from a Pseudomonas aeruginosa clinical isolate in France. Antimicrob Agents Chemother 2000; 44 : 891-7.
(51.) Rasheed JK, Anderson GJ, Yigit H, Queenan AM, Domenech-Sanchez A, Swenson JM, et al. Characterization of the extended-spectrum beta-lactamase reference strain, Klebsiella pneumoniae K6 (ATCC 700603), which produces the novel enzyme SHV-18. Antimicrob Agents Chemother 2000; 44 : 2382-8.
(52.) Chevalier J, Pages JM, Mallea M. In vivo modification of porin activity conferring antibiotic resistance to Enterobacter aerogenes. Biochem Biophys Res Commun 1999; 266 : 248-51.
(53.) Mazzariol A, Cornaglia G, Nikaido H. Contributions of the AmpC beta-lactamase and the AcrAB multidrug effiux system in intrinsic resistance of Escherichia coli K-12 to beta-lactams. Antimicrob Agents Chemother 2000; 44 : 1387-90.
(54.) Heritage J, Hawkey PM, Todd N, Lewis IJ. Transposition of the gene encoding a TEM-12 extended-spectrum beta-lactamase. Antimicrob Agents Chemother 1992; 36 : 1981-6.
(55.) Haeggman S, Lofdahl S, Burman LG. An allelic variant of the chromosomal gene for class A beta-lactamase K2, specific for Klebsiella pneumoniae, is the ancestor of SHV-1. Antimicrob Agents Chemother 1997; 41 : 2705-9.
(56.) Babini GS, Livermore DM. Are SHV beta-lactamases universal in Klebsiella pneumoniae? Antimicrob Agents Chemother 2000; 44 : 2230.
(57.) Preston KE, Venezia RA, Stellrecht KA. The SHV-5 extended-spectrum beta-lactamase gene of pACM1 is located on the remnant of a compound transposon. Plasmid 2004; 51 : 48-53.
(58.) Philippon A, Arlet G, Jacoby GA. Plasmid-determined AmpC-type beta lactamase. Antimicrob Agents Chemother 2002; 46 : 1-11.
(59.) Kurokawa H, Yagi T, Shibata N, Shibayama K, Arakawa Y. Worldwide proliferation of carbapenem-resistant gram-negative bacteria. Lancet 1999; 354 : 955.
(60.) Raimondi A, Traverso A, Nikaido H. Imipenem- and meropenem-resistant mutants of Enterobacter cloacae and Proteus rettgeri lack porins. Antimicrob Agents Chemother 1991; 35 : 1174-80.
(61.) Du Bois SK, Marriott MS, Amyes SG. TEM- and SHV-derived extended-spectrum beta-lactamases: relationship between selection, structure and function. J Antimicrob Chemother 1995; 35 : 7-22.
(62.) Brun-Buisson C, Legrand P, Philippon A, Montravers F, Ansquer M, Duval J. Transferable enzymatic resistance to third-generation cephalosporins during nosocomial outbreak of multiresistant Klebsiella pneumoniae. Lancet 1987; 2 : 302-6.
(63.) Marty L, Jarlier V. Surveillance of multiresistant bacteria: justification, role of the laboratory, indicators, and recent French data. Pathol Biol (Paris) 1998; 46 : 217-26.
(64.) Albertini MT, Benoit C, Berardi L, Berrouane Y, Boisivon A, Cahen PC, et al. Surveillance of methicillin-resistant Staphylococcus aureus (MRSA) and Enterobacteriaceae producing extended-spectrum beta-lactamase (ESBLE) in Northern France: a five-year multicentre incidence study. J Hosp Infec 2002; 52 : 107-13.
(65.) Jacoby GA, Medeiros AA, O'Brien TF, Pinto ME, Jiang H. Broad-spectrum, transmissible beta-lactamases. N Engl J Med 1988; 319 : 723-4.
(66.) National Nosocomial Infections Surveillance. National Nosocomial Infections Surveillance (NNIS) System Report, data summary from January 1992 to June 2002, issued August 2002. Am J Infect Control 2002; 30 : 458-75.
(67.) Boyd DA, Tyler S, Christianson S, McGeer A, Muller MP, Willey BM, et al. Complete nucleotide sequence of a 92-kilobase plasmid harboring the CTX-M-15 extended-spectrum beta-lactamase involved in an outbreak in long-term-care facilities in Toronto, Canada. Antimicrob Agents Chemother 2004; 48 : 3758-64.
(68.) Moland ES, Black JA, Hossain A, Hanson ND, Thomson KS, Pottumarthy S. Discovery of CTX-M-like extended-Spectrum beta-lactamases in Escherichia coli isolates from five U.S. states. Antimicrob Agents Chemother 2003; 47 : 2382-3.
(69.) Pitout JD, Hossain A, Hanson ND. Phenotypic and molecular detection of CTX-M-beta-lactamases produced by Escherichia coli and Klebsiella spp. J Clin Microbiol 2004; 42 : 5715-21.
(70.) Casellas JM, Goldberg M. Incidence of strains producing extended spectrum beta-lactamases in Argentina. Infection 1989; 17 : 434-6.
(71.) Radice M, Power P, Di Conza J, Gutkind G. Early dissemination of CTX-M-derived enzymes in South America. Antimicrob Agents Chemother 2002; 46 : 602-4.
(72.) Poirel L, Le Thomas I, Naas T, Karim A, Nordmann P. Biochemical sequence analyses of GES-1, a novel class A extended-spectrum beta-lactamase, and the class 1 integron In 52 from Klebsiella pneumoniae. Antimicrob Agents Chemother 2000; 44 : 622-32.
(73.) Bonnet R, Sampaio JL, Chanal C, Sirot D, De Champs C, Viallard JL, et al. A novel class A extended-spectrum beta-lactamase (BES-1) in Serratia marcescens isolated in Brazil. Antimicrob Agents Chemother 2000; 44 : 3061-8.
(74.) Mendes C, Hsiung A, Kiffer C, Oplustil C, Sinto S, Mimica I, et al. Evaluation of the in vitro activity of 9 antimicrobials against bacterial strains isolated from patients in intensive care units in Brazil: MYSTIC Antimicrobial Surveillance ProGram. Braz J Infect Dis 2000; 4 : 236-44.
(75.) Otman J, Cavassin ED, Perugini ME, Vidotto MC. An outbreak of extended-spectrum beta-lactamase-producing Klebsiella species in a neonatal intensive care unit in Brazil. Infect Control Hosp Epidemiol 2002; 23 : 8-9.
(76.) Bell JM, Turnidge JD, Gales AC, Pfaller MA, Jones RN. Prevalence of extended spectrum beta-lactamase (ESBL)-producing clinical isolates in the Asia-Pacific region and South Africa: regional results from SENTRY Antimicrobial Surveillance Program (1998-99). Diagn Microbiol Infect Dis 2002; 42 : 193-8.
(77.) Sader HS, Gales AC, Granacher TD, Pfaller MA, Jones RN. Prevalence of antimicrobial resistance among respiratory tract isolates in Latin America: results from SENTRY antimicrobial surveillance program (1997-98). Braz J Infect Dis 2000; 4 : 245-54.
(78.) Sader HS, Jones RN, Gales AC, Winokur P, Kugler KC, Pfaller MA, et al. Antimicrobial susceptibility patterns for pathogens isolated from patients in Latin American medical centers with a diagnosis of pneumonia: analysis of results from the SENTRY Antimicrobial Surveillance Program (1997). SENTRY Latin America Study Group. Diagn Microbiol Infect Dis 1998; 32 : 289-301.
(79.) Kariuki S, Corkill JE, Revathi G, Musoke R, Hart CA. Molecular characterization of a novel plasmid-encoded cefotaximase (CTX-M-12) found in clinical Klebsiella pneumoniae isolates from Kenya. Antimicrob Agents Chemother 2001; 45 : 2141-3.
(80.) Hanson ND, Smith Moland E, Pitout JD. Enzymatic characterization of TEM-63, a TEM-type extended spectrum beta-lactamase expressed in three different genera of Enterobacteriaceae from South Africa. Diagn Microbiol Infect Dis 2001; 40 : 199-201.
(81.) Pitout JD, Thomson KS, Hanson ND, Ehrhardt AF, Moland ES, Sanders CC. [beta]-Lactamases responsible for resistance to expanded-spectrum cephalosporins in Klebsiella pneumoniae, Escherichia coli, and Proteus mirabilis isolates recovered in South Africa. Antimicrob Agents Chemother 1998; 42 : 1350-4.
(82.) Poirel L, Weldhagen GF, De Champs C, Nordmann P. A nosocomial outbreak of Pseudomonas aeruginosa isolates expressing the extended-spectrum beta-lactamase GES-2 in South Africa. J Antimicrob Chemother 2002; 49 : 561-5.
(83.) Yu Y, Zhou W, Chen Y, Ding Y, Ma Y. Epidemiological and antibiotic resistant study on extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae in Zhejiang Province. Chin Med J (Engl) 2002; 115: 1479-82.
(84.) Jacoby GA, Medeiros A, O'Brien TF, Pinto ME. Jiang H. Broad-spectrum, transmissible beta-lactamases. N Engl J Med 1988; 319 : 723-4.
(85.) Lewis MT, Yamaguchi K, Beidenbach DJ, Jones RN. In vitro evaluation of cefepime and other broad spectrum beta lactams in 22 medical centres in Japan: a Phase II trial comparing two annual organism samples. The Japan Antimicrobial Resistance Study Group. Diagn Microbiol Infect Dis 1999; 35 : 307-15.
(86.) Kurokawa H, Yagi T, Shibata N, Shibayama K, Kamachi K, Arakawa Y. A new SHV derived extended spectrum beta-lactamase (SHV-24) that hydrolyzes ceftazidime through a single amino acid substitution (D 179G) in the loop. Antimicrob Agents Chemother 2000; 44 : 1725-7.
(87.) Chanawong A, M'Zali FH, Heritage J, Xiong JH, Hawkey PM. Three cefotaximases, CTX-M-9, CTX-M-13, and CTX-M-14, among Enterobacteriaceae in the People's Republic of China. Antimicrob Agents Chemother 2002; 46 : 630-7.
(88.) Komatsu M, Ikeda N, Aihara M, Nakamachi Y, Kinoshita S, Yamasaki K, et al. Hospital outbreak of MEN-l-derived extended spectrum beta-lactamase-producing Klebsiella pneumoniae. J Infect Chemother 2001; 7 : 94-101.
(89.) Pai H, Choi EH, Lee HJ, Hong JY, Jacoby GA. Identification of CTX-M-14 extended-spectrum beta-lactamase in clinical isolates of Shigella sonnei, Escherichia coli, and Klebsiella pneumoniae in Korea. J Clin Microbiol 2001; 39 : 3747-9.
(90.) Yu WL, Pfaller MA, Winokur PL, Jones RN. Cefepime MIC as a predictor of the extended-spectrum beta-lactamase type in Klebsiella pneumoniae, Taiwan. Emerg Infect Dis 2002; 8 : 522-4.
(91.) Turner PJ, Greenhalgh JM, Edwards JR, McKellar J. The MYSTIC (meropenem yearly susceptibility test information collection) programme. Int J Antimicrob Agents 1999; 13 : 117-25.
(92.) Turner PJ. Extended spectrum [beta]-1actamases. Clin Infect Dis 2005; 41 : S273-5.
(93.) Bauernfeind A, Casellas JM, Goldberg M, Holley M, Jungwirth R, Mangold P, et al. A new plasmidic cefotaximase from patients infected with Salmonella typhimurium. Infection 1992; 20 : 158-63.
(94.) Moland ES, Hanson ND, Black JA, Hossain A, Song W, Thomson KS. Prevalence of newer beta-lactamases in Gramnegative clinical isolates collected in the United States from 2001 to 2002. J Clin Microbiol 2006; 44 : 3318-24.
(95.) Ito H, Arakawa Y, Ohsuka S, Wacharotayankun R, Kato N, Ohta M. Plasmid-mediated dissemination of the metallo-beta-lactamase gene blaIMP among clinically isolated strains of Serratia marcescens. Antimicrob Agents Chemother 1995; 39 : 824-9.
(96.) Senda K, Arakawa Y, Ichiyama S, Nakashima K, Ito H, Ohsuka S, et al. PCR detection of metallo-beta-lactamase gene (blaIMP) in Gram-negative rods resistant to broad-spectrum beta-lactams. J Clin Microbiol 1996; 34 : 2909-13.
(97.) Shibata N, Doi Y, Yamane K, Yagi T, Kurokawa H, Shibayama K, et al. PCR typing of genetic determinants for metallo-beta-lactamases and integrases carried by Gram-negative bacteria isolated in Japan, with focus on the class 3 integron. J Clin Microbiol 2003; 41 : 5407-13.
(98.) Cornaglia G, Riccio ML, Mazzariol A, Lauretti L, Fontana R, Rossolini GM. Appearance of IMP-1 metallo-beta-lactamase in Europe. Lancet 1999; 353 : 899-900.
(99.) Koh TH, Babini GS, Woodford N, Sng LH, Hall LCM, Livermore DM. Carbapenem hydrolyzing IMP-1 beta-lactamase in Kleb. pneumoniae from Singapore. Lancet 1999; 353 : 2162.
(100.) Ga les AC, Menezes LC, Silbert S, Sader HS. Dissemination in distinct Brazilian regions of an epidemic carbapenem-resistant Pseudomonas aeruginosa producing SPM metallo--[beta]-lactamase. J Antimicrob Chemother 2003; 52 : 699-702.
(101.) Lee K, Lee WG, Uh Y, Ha GY, Cho J, Chong Y. VIM- and IMP-Type Metallo-[beta]-1actamase-producing Pseudomonas spp. and Acinetobacter spp. in Korean Hospitals. Emerg Infect Dis 2003; 9 : 868-71.
(102.) Goossens H, Malhotra Kumar S, Eraksoy H, Unal S, Grabein B, Masterton R. et al. MYSTIC study group: Results of two world wide surveys into physician awareness and perceptions of extended spectrum spectrum beta lactamases. Clin Microbiol Infect 2004; 10 : 760-2.
(103.) Pfaller MA, Segreti J. Overview of the epidemiological profile and laboratory detection of extended-spectrum beta-lactamases. Clin Infect Dis 2006; 42 (Suppl) 4 : S153-63.
(104.) Komatsu M, Aihara M, Shimakawa K, Iwasaki M, Nagasaka Y, Fukuda S, et al. Evaluation of MicroScan ESBL confirmation panel for Enterobacteriaceae-producing, extended-spectrum beta-lactamases isolated in Japan. Diagn Microbiol Infect Dis 2000; 46 : 125-30.
(105.) Rodriguez-Bano J, Navarro MD, Romero L, Muniain MA, de Cueto M, Rios MJ, et al. Bacteremia due to extended-spectrum beta-lactamase-producing Escherichia coli in the CTX-M era: a new clinical challenge. Clin Infect Dis 2006; 43 : 1407-14.
(106.) Hansotia JB, Agarwal V, Pathak AA, Saoji AM. Extended spectrum beta-lactamase mediated resistance to third generation cephalosporins in Klebsiella pneumoniae in Nagpur, central India. Indian J Med Res 1997; 105 : 158-61.
(107.) Mathur P, Kapil A, Das B, Dhawan B. Prevalence of extended spectrum beta lactamase producing Gram negative bacteria in a tertiary care hospital. Indian J Med Res 2002; 115 : 153-7.
(108.) Grover SS, Sharma M, Pasha ST, Singh G, Lal S. Antimicrobial susceptibility pattern and prevalence of extended spectrum beta-lactamase (ESBLs) producing strains of Klebsiella pneumoniae from a major hospital in New Delhi. J Commun Dis 2004; 36 : 17-26.
(109.) Datta P, Thakur A, Mishra B, Gupta V. Prevalence of clinical strains resistant to various [beta]-1actamases in a tertiary care hospital in India. Jpn J Infect Dis 2004; 57 : 146-9.
(110.) Mohanty S, Singhal R, Sood S, Dhawan B, Das BK, Kapil A. Comparative in vitro activity of beta-lactam/beta-lactamase inhibitor combinations against Gram negative bacteria. Indian J Med Res 2005; 122 : 425-8.
(111.) Gupta V, Datta P. Extended-spectrum beta-lactamases (ESBL) in community isolates from North India: frequency and predisposing factors. Int J Infect Dis 2007; 11 : 88-9.
(112.) Babypadmini S, Appalaraju B. Extended spectrum beta lactamases in urinary isolates of E.coli & K.pneumoniae--prevalence and susceptibility pattern in a tertiary care hospital. Indian J Med Microbiol 2004; 22 : 172-4.
(113.) Tankhiwale SS, Jalgaonkar SV, Ahamad S, Hassani U. Evaluation of extended spectrum beta lactamase in urinary isolates. Indian J Med Res 2004; 120 : 553-6.
(114.) Subha A, Ananthan S, Alavandi SV. Extended spectrum beta lactamase production and multidrug resistance in Klebsiella species isolates from children under five with intestinal & extraintestinal infections. Indian J Med Res 2001 ; 113 : 181-5.
(115.) Vinodkumar CS, Neelagund YF. Emergence of extended spectrum beta lactamase mediated resistance in neonatal septicemia. Indian J Pathol Microbiol 2006; 49 : 616-9.
(116.) Jain A, Roy I, Gupta MK, Kumar M, Agarwal SK. Prevalence of extended-spectrum beta-lactamase-producing Gramnegative bacteria in septicaemic neonates in a tertiary care hospital. J Med Microbiol 2003; 52 : 421-5.
(117.) Ratna AK, Menon I, Kapur I, Kulkarni R. Occurrence & detection of Amp C 13-1actamases at a referral hospital in Karnataka. Indian J Med Res 2003; 118 : 29-32.
(118.) Navaneeth BV, Sridaran D, Sahay D, Belwadi MRS. A preliminary study on metallo [beta]-1actamase producing Pseudomonas aeruginosa in hospitalized patients. Indian J Med Res 2002; 116 : 264-7.
(119.) Hemlatha V, Sekar U, Kamat V. Detection of metallo betalactamase producing Pseudomonas aeruginosa in hospitalized patients. Indian J Med Res 2005; 122 : 148-52.
(120.) Gupta V, Datta P, Chander J. Prevalence of metallo [beta]-lactamases (MBL) producing Pseudomonas and Acinetobacter spp in a tertiary care hospital in India. J Infect 2006; 52 : 311-4.
(121.) Jones RN, Rhomberg PR, Varnam DJ, Mathai D. A comparison of the antimicrobial activity of meropenem and selected broadspectrum antimicrobials tested against multi-drug resistant Gram-negative bacilli including bacteraemic Salmonella spp.: initial studies for the MYSTIC programme in India. Int J Antimicrob Agents 2002; 20:426-31.
(122.) Grover SS, Sharma M, Chattopadhya D, Kapoor H, Pasha ST, Singh G. Phenotypic and genotypic detection of ESBL mediated cephalosporin resistance in Klebsiella pneumoniae: emergence of high resistance against cefepime, the fourth generation cephalosporin. J Infect 2006; 53 : 279-88.
(123.) Ensor VM, Shahid M, Evans JT, Hawkey PM. Occurrence, prevalence and genetic environment of CTX-M beta lactamases in Enterobacteriaceae from Indian hospitals. J Antimicrob Chemother 2006; 58 : 1260-3.
(124.) Katsanis GP, Spargo J, Ferraro M J, Sutton Hacoby GA. Detection of Klebsiella pneumoniae and Escherichia coli strains producing expanded-spectrum beta-lactamases. J Clin Microbiol 1994; 32 : 691-6.
(125.) National Committee for Clinical Laboratory Standards. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. Approved Standard M7-A5 and informational Supplement M100-S10. Wayne, PA: National Committee for Clinical Laboratory Standards; 2000.
(126.) Clinical Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing, XVI International Supplement (M 100-S 16). Wayne, Pennsylvania, USA: National Committee for Clinical Laboratory Standards; 2006.
(127.) Sturenburg E, Mack D. Extended spectrum beta Lactamases: implications for the clinical microbiology department, therapy, and infection control. J Infect 2003; 47 : 273-95.
(128.) Giamarellou H. Multidrug resistance in Gram negative bacteria that produce extended spectrum [beta]-1actamases (ESBLs). Clin Microbiol Infect 2005:11 : 1-16.
(129.) Jarlier V, Nicolas MH, Fournier G, Philippon A. Extended broad spectrum beta lactamases conferring transferable resistance to newer beta lactam agents in Enterobacteriaceae: hospital prevalence and susceptibility patterns. Rev Infect Dis 1988; 10 : 867-78.
(130.) Carter MW, Oakton KJ, Warner M, Livermore DM. Detection of extended spectrum beta lactamases in Klebsiellae with the Oxoid combination disk method. J Clin Microbiol 2000; 38 : 4228-32.
(131.) Thomson KS, Sanders CC. Detection of expanded-spectrum beta-lactamases in members of the family Enterobacteriaceae: comparison of the double disk and three-dimensional tests. Antimicrobial Agents Chemother 1992; 36 : 1877-82.
(132.) Tzepeli E, Giakkoupi P, Sofianou D, Loukova V, Kemeroglou A, Tsakris A. Detection of extended-spectrum beta-lactamases in clinical isolates of Enterobacter cloacae and Enterobacter aerogenes. J Clin Microbiol 2000; 38 : 542-6.
(133.) Waksh TR, Bolmstrom A, Qwarnstrom A, Gales A. Evaluation of a new E test for detecting metallo [beta]-lactamase in routine clinical testing. J Clin Microbiol 2002; 40 : 2755-9.
(134.) Yong D, Lee K, Yum JH, Shin HB, Rossolini GM, Ch Y. Imipenem-EDTA disk method for differentiation of metallo [beta]-lactamase producing clinical isolates of Pseudomonas spp. and Acinetobacter spp. J Clin Microbiol 2002; 42 : 3798-801.
(135.) Yagi T, Wachino J, Kurokawa H, Suzuki S, Yamane K, Doi Y, et al. Practical methods using boronic acid compounds for identification of Class C [beta]-lactamase producing Klebsiella pneumoniae and Escherichia coli. J Clin Microbiol 2005; 43 : 2551-8.
(136.) Coudran PE, Moland ES, Thomson KS. Occurrence and detection of Amp-C beta-lactamases among Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis isolates at a Veterans Medical Centre. J Clin Microbiol 2000; 38 : 1791-6.
(137.) Singhal S, Mathur T, Khan S, Upadhyay DJ, Chugh S, Gaind R, et al. Evaluation of methods for Amp C [beta]-1actamase in Gram negative clinical isolates from tertiary care hospitals. Indian J Med Microbiol 2005; 23 : 120-4.
(138.) Rice LB, Willey SH, Papanicolaou GA, Mederiros AA, Elicopoulos GM, Moellering RC Jr, et al. Outbreak of ceftazidime resistance caused by expanded-spectrum beta-lactamases at a Massachusetts chronic-care facility. Antimicrob Agents Chemother 1990; 34 : 2193-9.
(139.) Walther-Rasmussen J, Hoiby N. Plasmid-borne AmpC beta-lactamases. Can J Microbiol 2002; 48 : 479-3.
(140.) Karadenizli A, Mutlu B, Okay E, Kotayli F, Vahaboglu H. Piperacillin with and without tazobactam against extended spectrum beta lactamase-producing Pseudomonas aeruginosa in a rat thigh abscess model. Chemotherapy 2001; 47 : 292-6.
(141.) Linden PK, Kusne S, Coley K, Fontes P, Kramer DJ, Paterson D. Use of parenteral colistin for the treatment of serious infection due to antimicrobial resistant Pseudomonas aeruginosa. Clin Infect Dis 2003; 37 : E154-60.
(142.) De Champs C, Sauvant ME Chanal C, Sirot D, Gazuy N, Malhuret R, et al. Prospective survey of colonization and infections caused by expanded-spectrum beta-lactamase-producing members of the family Enterobacteriaceae in an intensive care unit. J Clin Microbiol 1989; 12 : 2887-90.
Department of Microbiology, Government Medical College & Hospital, Chandigarh, India
Reprint requests: Dr Varsha Gupta, Professor, H.No.3109, Sector 48-D, Chandigarh 160047, India e-mail: firstname.lastname@example.org
|Gale Copyright:||Copyright 2007 Gale, Cengage Learning. All rights reserved.|