Kegg Pathway: beta-Lactam resistance

Hautarzt. 2008 Jul 19;
Mempel M, Kerzl R, Ring J

Because of the increasing incidence of resistance to beta-Lactam antibiotics, dermatologists will be increasingly confronted with methicillin-resistant S. aureus (MRSA) strains which display a great variability of their virulence factors. In view of the high mortality of systemic MRSA infections (estimated 700-1.500 deaths per year in Germany), dermatologists should be well aware of the various aspects of diagnosis, therapy and prevention of this problem bacteria. Adequate screening measures must be in place to identify high-risk patients and institute appropriate prophylactic measures and therapy. If only colonization is present, topical antiseptic measures are sufficient. If an infection is present, either systemic or topical therapeutic approaches may be indicated. We review the role of MSRA infection and colonization in skin diseases.

Vojnosanit Pregl. 2008 May; 65(5): 377-82

BACKGROUND/AIM: In many hospitals in the world and in our country, the spread of methicillin-resistant Staphylococcus aureus (MRSA) is so wide that nowdays vancomycin is recommended for empiric treatment of staphylococcal life threatening infections (sepsis, pneumonia) instead of beta-Lactam antibiotics. The aim of this study was to determine the production of beta-Lactamases in hospital and community isolates of staphyloococus aureus, i.e. hospital associated MRSA (HA-MRSA) and community associated MRSA (CA-MRSA), the presence of homogeneous and heterogeneous type of methicillin resistance, and border-line resistance in Staphylococcus aureus (BORSA). The aim of this study was also to determine if there was a statistically significant difference between mechanisms of resistance in HA-MRSA and CA-MRSA. METHODS: A total 216 clinical Staphylococcus aureus isolates from the General Hospital in the town of Cuprija and 186 ambulance Staphylococcus aureus isolates from the community were examined for the presence of methicillin-resistance using disk-diffusion test with penicillin disk (10 ij), oxacillin disk (1 microg) and cefoxitin disk (30 microg). beta-Lactamases production was detected by nitrocefin disk and beta-Lactamase tablets. Determination of oxacillin minimum inhibitory concentracion (MIC) was done by agar-dilution method. RESULTS: The prevalence of HA-MRSA was 57.4%, and CA-MRSA was 17.7% (p < 0.05). There was a higher rate of heterogeneous type of resistance among clinical MRSA isolates (11.1%) compared with ambulance ones (3.8%) (p < 0.05). The rates of beta-Lactamases production were similar among hospital associated isolates (97.5%), as well as in the community associated isolates (95.5%) (p > 0.05). There were 4.6% of BORSA hospital isolates and 3.3% of BORSA ambulance isolates (p > 0.05). CONCLUSION: The frequency of MRSA isolates in hospital was significantly higher than in community, as well as the heterogeneous type of resistance. The frequency of BORSA isolates and production of beta-Lactamases were higher among hospital Staphylococcus aureus isolates, but the difference is not significant.

Int J Antimicrob Agents. 1997 Sep; 9(2): 107-12
Bert F, Lambert-Zechovsky N

The susceptibility to ticarcillin, piperacillin, ceftazidime, aztreonam, tobramycin, amikacin, ciprofloxacin and fosfomycin of 3876 strains of Pseudomonas aeruginosa isolated during the period 1989-1996 in a French hospital was investigated. The most frequently active agents were amikacin and ceftazidime to which 13.3% and 16.1% of the isolates were resistant. Analysis of beta-Lactam susceptibility patterns suggested that cephalosporinase derepression and intrinsic resistance were the predominant underlying mechanisms. There was a trend towards a decline in susceptibility to beta-Lactams, aminoglycosides and ciprofloxacin over time. Multiresistance was frequent, mainly in O11 and O12 isolates.

J Biotechnol. 2008 Apr 8;
Schlüter A, Krause L, Szczepanowski R, Goesmann A, Pühler A

Plasmid metagenome nucleotide sequence data were recently obtained from wastewater treatment plant (WWTP) bacteria with reduced susceptibility to selected antimicrobial drugs by applying the ultrafast 454-sequencing technology. The sequence dataset comprising 36,071,493 bases (346,427 reads with an average read length of 104 bases) was analysed for genetic diversity and composition by using a newly developed bioinformatic pipeline based on assignment of environmental gene tags (EGTs) to protein families stored in the Pfam database. Short amino acid sequences deduced from the plasmid metagenome sequence reads were compared to profile hidden Markov models underlying Pfam. Obtained matches evidenced that many reads represent genes having predicted functions in plasmid replication, stability and plasmid mobility which indicates that WWTP bacteria harbour genetically stabilised and mobile plasmids. Moreover, the data confirm a high diversity of plasmids residing in WWTP bacteria. The mobile organic peroxide resistance plasmid pMAC from Acinetobacter baumannii was identified as reference plasmid for the most abundant replication module type in the sequenced sample. Accessory plasmid modules encode different transposons, insertion sequences, integrons, resistance and virulence determinants. Most of the matches to Transposase protein families were identified for transposases similar to the one of the chromate resistance transposon Tn5719. Noticeable are hits to beta-Lactamase protein families which suggests that plasmids from WWTP bacteria encode different enzymes possessing beta-Lactam-hydrolysing activity. Some of the sequence reads correspond to antibiotic resistance genes that were only recently identified in clinical isolates of human pathogens. EGT analysis thus proofed to be a very valuable method to explore genetic diversity and composition of the present plasmid metagenome dataset.

J Inorg Biochem. 2008 May 28;
Oelschlaeger P

Metallo-beta-Lactamases (MBLs) confer antibiotic resistance to bacteria by hydrolyzing and thus inactivating beta-Lactam antibiotics. They have raised concerns due to their broad substrate spectra, the absence of clinically useful inhibitors, and their rapid dissemination. The resulting threat to public health is enhanced by their potential to evolve into even more efficient enzymes through mutation. This is based on the assumption that these enzymes are relatively novel and in the beginning of their natural evolution. Their ongoing evolution has been manifested by the isolation of improved enzyme variants from clinical isolates, and improved variants have been generated under controlled laboratory conditions. Our ability to mimic and eventually predict the evolution of MBLs will likely put us into a better position to effectively combat MBL-conferred antibiotic resistance. This review summarizes how various approaches in recent years have brought us closer to that goal.

N Engl J Med. 2008 Jul 3; 359(1): 85-7
Daum RS

Ann Intern Med. 2008 Jul 1; 149(1): 67; author reply 68-9
Diekema D

Ann Intern Med. 2008 Jul 1; 149(1): 67-8; author reply 68-9
Nelson RB

Ann Intern Med. 2008 Jul 1; 149(1): 65; author reply 66
Katz KA, Bernstein KT, Klausner JD

AIDS Read. 2008 May; 18(5): 266-8
Gaughan EM, Ritter ML, Kumar PN, Timpone JG

Fusion inhibitors are novel antiretroviral agents, administered as subcutaneous injections, approved for use in treatment-experienced HIV-infected patients. HIV-infected patients are at increased risk for Staphylococcus aureus colonization, specifically with methicillin-resistant S aureus (MRSA), and subsequent systemic infection. We present the cases of 2 patients without a history of MRSA infection in whom a series of severe S aureus infections developed after fusion inhibitor therapy.

Am J Med. 2008 Jul; 121(7): 572-6
Yates AB

Patients with a history of penicillin allergy pose a treatment dilemma. Unnecessary avoidance of this relatively nontoxic class of drugs exposes the patient to potentially more toxic drugs, increases health care costs, and contributes to the development of antibiotic resistance. Yet for those who truly have allergy or other serious adverse reactions to beta-Lactams, the use of alternate drugs is a must. This article reviews current management strategies to determine which patients are good candidates for reintroduction of beta-Lactams and which patients should continue avoidance.

J Antimicrob Chemother. 2008 Jun 25;
Karami N, Hannoun C, Adlerberth I, Wold AE

Objectives To compare the colonization dynamics of ampicillin-resistant and ampicillin-susceptible Escherichia coli strains in the infantile intestinal microbiota. Methods We followed 128 infants over the first year of life with regular quantitative faecal cultures and recordings of antibiotic treatment. E. coli strains were quantified, and their resistance pattern and carriage of beta-Lactamase genes (TEM, SHV and OXA), phylogenetic group (A, B1, B2 or D), virulence gene profile (fimA, papC, sfaD/E, kfiC neuB, hlyA and iutA) and time of persistence in the microbiota were determined. Results Twelve percent (n = 32) of the E. coli strains were resistant to ampicillin, as they carried the bla(TEM) (84%) or bla(SHV) genes. Ampicillin-resistant strains belonged mostly to phylogenetic group D and carried pap genes (P = 0.023) significantly more often than ampicillin-susceptible strains due to a strong association between carriage of pap and bla(SHV). In 31 of 32 cases, colonization by ampicillin-resistant strains occurred in infants not previously treated with beta-Lactam antibiotics. Ampicillin-resistant strains were equally capable as susceptible ones of persisting in the intestinal microbiota and did not have lower faecal population counts. Genes encoding beta-Lactamases were in most cases retained during the entire colonization period. Conclusions The results suggest that ampicillin-resistant E. coli strains are not hampered in their colonizing capacity, and beta-Lactamase genes, therefore, may only slowly be eliminated from the commensal E. coli strain pool.

Anaesthesia. 2008 Jul; 63(7): 764-6
Baldwin LN, Lowe AD

We report a case of community acquired methicillin resistant Staphylococcus aureus pneumonia. The causative organism was positive for the toxin Panton-Valentine Leukocidin. This resulted in a severe pneumonia requiring a prolonged stay on our intensive care unit. This infection is becoming more common in the United Kingdom. It can cause a far more aggressive illness than the hospital acquired infection with a high mortality if it becomes an invasive infection. The Department of Health has recently produced interim guidelines for its treatment which we have also reviewed.

J Theor Biol. 2008 Jun 4;
Murphy JT, Walshe R, Devocelle M

An agent-based model of bacteria-antibiotic interactions has been developed that incorporates the antibiotic-resistance mechanisms of Methicillin-Resistant Staphylococcus aureus (MRSA). The model, called the Micro-Gen Bacterial Simulator, uses information about the cell biology of bacteria to produce global information about population growth in different environmental conditions. It facilitates a detailed systems-level investigation of the dynamics involved in bacteria-antibiotic interactions and a means to relate this information to traditional high-level properties such as the Minimum Inhibitory Concentration (MIC) of an antibiotic. The two main resistance strategies against beta-Lactam antibiotics employed by MRSA were incorporated into the model: beta-Lactamase enzymes, which hydrolytically cleave antibiotic molecules, and penicillin-binding proteins (PBP2a) with reduced binding affinities for antibiotics. Initial tests with three common antibiotics (penicillin, ampicillin and cephalothin) indicate that the model can be used to generate quantitatively accurate predictions of MICs for antibiotics against different strains of MRSA from basic cellular and biochemical information. Furthermore, by varying key parameters in the model, the relative impact of different kinetic parameters associated with the two resistance mechanisms to beta-Lactam antibiotics on cell survival in the presence of antibiotics was investigated.

Chang Gung Med J. 2008 Mar-Apr; 31(2): 117-24
Hsieh YC, Lee WS, Shao PL, Chang LY, Huang LM

Streptococcus pneumoniae, an important pathogen causing sepsis, sinusitis, otitis media, bacterial meningitis and bacterial pneumonia, results in global morbidity and mortality each year. The burden of pneumococcal disease is highest in children and the elderly. Treatment of pneumococcal infection has been hampered by the complexity of the host immune response. In recent decades, the increase of S. pneumoniae strains' resistance to beta-Lactam antibiotics and other classes of antimicrobials has made treatment even more complicated. Fortunately, the advent of heptavalent conjugate vaccine confers a high degree of protection against pneumococcal disease and colonization caused by vaccine serotype strains. After the introduction of conjugate pneumococcal vaccine, invasive pneumococcal disease caused by vaccine serotypes and antibiotic-resistant isolates has been reduced. However, naturally transformable pneumococci may escape vaccine-induced immunity by switching their capsular genes to non-vaccine serotypes. Development of cheaper, serotype-independent vaccines based on a combination of protein antigens should be pursued.

Consum Rep. 2008 Feb; 73(2): 50-1

BMJ. 2008 Jun 21; 336(7658): 1429-33
Durrington HJ, Summers C

Nephrol Dial Transplant. 2008 Jun 23;
Zvonar R, Natarajan S, Edwards C, Roth V

BACKGROUND: Vancomycin is frequently prescribed for the management of infections in haemodialysis patients. We evaluated the appropriateness of vancomycin use in our chronic haemodialysis population. METHODS: Charts of all chronic haemodialysis patients who received vancomycin between 1 March 2003 and 1 March 2004 were retrospectively reviewed. Indication was assessed according to the modified Hospital Infection Control Practices Advisory Committee guidelines for vancomycin prescription. The prescribed dosing regimens were evaluated. RESULTS: A total of 163 courses of vancomycin in 105 patients were assessed. Of all courses, 88% were considered to be initially appropriate, but this decreased to 63% once culture and sensitivity results were available. Use of vancomycin for the management of beta-Lactam-sensitive organisms accounted for the majority of inappropriate use. The most common vancomycin-dosing regimen prescribed was 500 mg intravenously at each haemodialysis session (51%); however, considerable variability was observed. CONCLUSIONS: Although the initial indication for vancomycin use was generally appropriate, inappropriate continuation of this antibiotic, failure to obtain proper cultures to guide therapy and potentially subtherapeutic dosing regimens were some of the challenges identified. Centres providing chronic haemodialysis should take steps to optimize vancomycin prescription to improve clinical outcomes and reduce the risk of antimicrobial resistance.

Eur J Clin Microbiol Infect Dis. 2008 Jun 19;
Xiao YH, Wang J, Li Y,

The aim of this study was to establish a nationwide antimicrobial resistant surveillance network and obtain information on bacterial resistance in China. A total of 4075 clinical bacterial isolates were collected from 17 hospitals in 15 cities throughout China. Antibacterial minimal inhibitory concentrations (MICs) were determined by the standard agar dilution method recommended by Clinical and Laboratory Standards Institute. The results of the MICs revealed the following bacterial resistance characteristics. Oxacillin resistance was shown by 62.9% of Staphylococcus aureus and 82.89% of Staphylococcus epidermidis strains. Penicillin non-sensitivity was show by 40.7% of the Streptococcus pneumoniae strains, which included 10.5% penicillin-resistant strains and 30.2% penicillin-intermediate strains. Five strains of Enterococci were vancomycin-intermediate, but all Enterococci strains were sensitive to teicoplanin. All Staphylococci were susceptible to glycopeptides. A high resistance to macrolides was a predominant characteristic of the Gram-positive cocci. Enterobacteriaceae strains were clearly resistant to the third generation cephalosporins, with the exception of ceftazidime, and the resistance rates ranged from 20 to 70%. About 65% of the Escherichia coli strains were resistant to fluoroquinolones. Carbapenems remained highly active against all the target bacteria. Latamoxef, piperacillin/tazobactam, cefoperazone/sulbactam and cefepime were all active against Enterobacteriaceae, which showed resistant rates of less than 10%. Imipenem resistance was found in 10.6% of Pseudomonas aeruginosa and 10.4% of Acinetobacter baumannii strains, most of which were multidrug resistant isolates. Combinations of beta-Lactam/beta-Lactamase inhibitor and fluoroquinolones also had potent antibacterial activity against non-fermenters. Amikacin was active against Enterobacteriaceae and P. aeruginosa. In conclusion, methicillin-resistant Staphylococci, penicillin-insensitive S. pneumoniae, macrolides-resistant Gram-positive cocci, cephalosporin-resistant Enterobacteriaceae, multidrug-resistant nonfermenters and fluoroquinolone-resistant E. coli were revealed to be the most serious problems in terms of bacteria resistance in China. No glycopeptides-resistant Staphylococcus strains were isolated, and the appearance of glycopeptides-resistant Enterococci was seldom.

J Drugs Dermatol. 2008 Jun; 7(6): 597-601
Terushkin V, Brownell I