Isolation of a Klebsiella pneumoniae Isolate of Sequence Type 258 Producing KPC-2 Carbapenemase in Korea / 대한진단검사의학회지

Carbapenem-resistant Klebsiella pneumoniae isolates producing K. pneumoniae carbapenemases (KPC) were first reported in the USA in 2001, and since then, this infection has been reported in Europe, Israel, South America, and China. In Korea, the first KPC-2-producing K. pneumoniae sequence type (ST) 11 strain was detected in 2010. We report the case of a patient with a urinary tract infection caused by KPC-2-producing K. pneumoniae. This is the second report of a KPC-2-producing K. pneumoniae infection in Korea, but the multilocus sequence type was ST258. The KPC-2-producing isolate was resistant to all tested beta-lactams (including imipenem and meropenem), amikacin, tobramycin, ciprofloxacin, levofloxacin, and trimethoprim-sulfamethoxazole, but was susceptible to gentamicin, colistin, polymyxin B, and tigecycline. The KPC-2-producing isolate was negative to phenotypic extended-spectrum beta-lactamase (ESBL) and AmpC detection tests and positive to modified Hodge test and carbapenemase inhibition test with aminophenylboronic acid.

[Frequency of extended-spectrum beta-lactamase [ESBL] multidrugresistance produced by Pseudomonas aeruginosa isolated from clinical and environmental specimens in Kashan Shahid Beheshti hospital during 2010-11]

Pseudomonas aeruginosa is among the most important nosocomial bacterial infections with innate resistance to many antibiotics. This study was designed to evaluate the frequency of extended-spectrum beta-lactamase [ESBL] multidrug-resistance produced by P. aeruginosa isolated from clinical and environmental specimens in Kashan Shahid Beheshti hospital. This descriptive study was conducted on clinical isolates [n=76] of P. aeruginosa from Kashan Shahid Beheshti hospital during 2010-11. Antibiotic susceptibility testing for eight antimicrobial agents was carried out according to the clinical and laboratory standards institute [CLSI] guidelines and ESBL-producing strains were confirmed using double-disk diffusion test. MDR-isolates were defined as those resistant to three or more classes of antibiotics. Among all P. aeruginosa isolates, the highest resistance was seen for piperacillin, imipenem, cefotaxime, ceftriaxone, gentamicin, ceftazidime, aztreonam and ciprofloxacin, respectively. Seven strains [9.2%] were ESBL-positive. Twenty-seven percent of the isolates were resistant to at least three classes of antibiotics; 8 out of 14 tracheal discharges; 4 out of 9 wound and 2 out of 3 blood samples were MDR. The study emphasizes the high frequency of MDR-P. aeruginosa in clinical and environmental specimens isolated from this hospital. Imipenem resistance in MDR-P.aeruginosa isolates is also high in this study. This calls for strict infection control measures to prevent further microbial spread

Betalactámicos con inhibidores de betalactamasas: Amoxicilina-sulbactam / Betalactam antibiotics combined with bectalactamases inhibitors: Amoxicillin-sulbactam

La producción de betalactamasas constituye uno de los principales mecanismos de resistencia bacteriana a los antibióticos betalactámicos. La utilización de inhibidores de betalactamasas en combinación con antibióticos betalactámicos permite la inactivación de determinadas betalactamasas producidas por gérmenes Gram positivos, Gram negativos, anaerobios, y aun por micobacterias. Los inhibidores de betalactamasas representan una alternativa terapéutica mejorada respecto del resto de los betalactámicos al asegurar, en la mayoría de los casos, un mayor espectro antimicrobiano comparado con el de sus análogos. La actividad enzimática de las betalactamasas está dirigida específicamente a la hidrólisis del anillo betalactámico, con producción de un compuesto sin actividad antibacteriana. De acuerdo con su posición genómica dentro de los microorganismos, las betalactamasas pueden ser cromosómicas o plasmídicas. Actualmente existen tres inhibidores de betalactamasas localmente disponibles: ácido clavulánico, sulbactam y tazobactam. De ellos, sólo el sulbactam posee actividad antimicrobiana intrínseca sobre las proteínas ligadoras de penicilina. La experiencia clínica acumulada durante más de 20 años confirma que las combinaciones de betalactámicos-inhibidores de betalactamasas son efectivas en el tratamiento empírico inicial de infecciones respiratorias, intraabdominales, urinarias y ginecológicas, incluidas las de origen polimicrobiano. En el caso particular de amoxicilina-sulbactam, la evidencia citada indica que esta combinación es efectiva para el tratamiento de absceso periamigdalino, otitis media, sinusitis, neumonía extrahospitalaria, exacerbación aguda de enfermedad pulmonar obstructiva crónica (EPOC), infección del tracto urinario e infecciones ginecoobstétricas. Por su espectro y propiedades farmacológicas, la combinación amoxicilina-sulbactam constituye una excelente opción también para el tratamiento de infecciones de piel y partes blandas e infecciones intraabdominales.

Betalactamases production is one of the main bacterial resistance mechanisms to betalactam antibiotics. The use of bectalactamases inhibitors combined with betalactam antibiotics allows the inactivation of certain betalactamases produced by Gram positive, Gram negative and anaerobic organisms, and even by mycobacteria. Betalactamases inhibitors are an improved therapeutic alternative compared with the other betalactam since, in most cases, they cover a wider antimicrobial spectrum than their analogues. Betalactamases enzimatic activity is specifically directed to the betalactam ring hydrolisis, producing a compound without antibacterial activity. According to their genomic position within microorganisms, betalactamases can be either chromosomic or plasmidic. Currently there are three betalactamases inhibitors locally available: clavulanic acid, sulbactam and tazobactam. Of them, only sulbactam has an intrinsic antimicrobial activity against penicillin binding proteins. The clinical experience from over 20 years confirms that the combination of betalactam antibiotics is effective in the empirical initial treatment of respiratory, intraabdominal, urinary tract and gynecologic infections, including those of polymicrobial origin. In the specific case of amoxicillin-sulbactam, experiences have shown the effectiveness of the combination in the treatment of peritonsillar abscess, otitis media, sinusitis, community acquired pneumonia, acute exacerbation of chronic obstructive pulmonar disease (COPD), urinary tract infection and obstetric/ gynecologic infections. The spectrum and pharmacologic properties of this combination makes it also an excellent option for the treatment of skin/soft tissue and intraabdominal infections.

Sensitivity pattern of gram negative bacilli to three beta-lactam/beta-lactamase inhibitor combinations using the automated API system.

PURPOSE: To evaluate the spectrum of activity of three beta-lactamase inhibitors such as amoxicillin/ clavulanic acid, ticarcillin/ clavulanic acid and piperacillin/ tazobactam in comparison to cephalosporins against gram negative bacilli. METHODS: Gram-negative bacilli isolated from the clinical specimens received in the laboratory were included in the study. Using the API system (bioMiotarieux) during a one-year period, a total of 1,252 Enterobacteriaceae and 385 non-fermenters were evaluated. RESULTS: The percentage resistance of the Enterobacteriaceae isolates was 82.92% to amoxicillin/ clavulanic acid, 58.22% to ticarcillin/clavulanic acid and 22.44% to piperacillin/tazobactam respectively. Pseudomonas aeruginosa showed resistance of 96% to ticarcillin/ clavulanic acid and 61% to piperacillin/ tazobactam and Acinetobacter baumannii showed 49% resistance to ticarcillin/ clavulanic acid and 77% resistance to piperacillin/ tazobactam respectively. The isolates exhibited high resistance to all the generations of cephalosporins and the other groups of antibiotics except carbapenems. CONCLUSIONS: Piperacillin/tazobactam was found to be the most active combination of the three against Enterobacteriaceae and Pseudomonas spp. and ticarcillin/clavulanic acid against Acinetobacter spp. and Stenotrophomonas maltophilia.

Comparative in vitro activities of seven new beta-lactams, alone and in combination with beta-lactamase inhibitors, against clinical isolates resistant to third generation cephalosporins

We examined the drug susceptibility pattern of Gram-negative bacilli to seven new beta-lactams. A total of 277 non-duplicate gramnegative bacilli strains belonging to the Enterobacteriaceae family, Pseudomonas and Acinetobacter species, isolated from various clinical samples were tested for susceptibility to imipenem, piperacillin/tazobactam, cefoperazone/sulbactam, ticarcillin/clavulanate, cefdinir, cefepime and cefpirome with the disk diffusion technique. The percentage resistance was low for imipenem (7.2 percent), piperacillin/tazobactam (2.8 percent), cefoperazone/sulbactam (5.4 percent). However, a high frequency of resistance was observed to ticarcillin/clavulanate (83.9 percent), cefdinir (70.6 percent), cefepime (45.5 percent) and cefpirome (84.4 percent). We conclude that imipenem, piperacillin/tazobactam and cefoperazone/sulbactam are effective antibiotics in our environment, whereas ticarcillin/clavulanate, cefdinir, cefepime and cefpirome are relatively uneffective.

Comparative in vitro activity of beta-lactam/beta-lactamase inhibitor combinations against gram negative bacteria.

BACKGROUND & OBJECTIVE: Currently, the use of beta-lactamase inhibitors in combination with beta-lactam antibiotics represents an effective measure to combat a specific resistance mechanism of beta-lactamase producing organisms. Knowledge about the susceptibility profile of bacteria to different combination agents available is essential to guide appropriate treatment of severe infections in hospitalized patients. The present study compares the in vitro activity of three commercially available beta-lactam/beta-lactamase inhibitor combinations (piperacillin/tazobactam, cefoperazone/sulbactam, ticarcillin/clavulanic acid) against beta-lactamase producing gram negative bacteria in a tertiary care hospital in north India. METHODS: A total of 9004 consecutively isolated extended spectrum beta-lactamase (ESBL) producing gram negative bacteria isolated from various clinical samples from patients admitted to the All India Institute of Medical Sciences, New Delhi, from September 2003 to August 2004 were included in the study. These isolates were screened for ESBL production by the inhibitor based test recommended by the National Committee for Clinical Laboratory Standards (NCCLS). Antibiotic susceptibility testing was carried out by disc diffusion method as per NCCLS guidelines. RESULTS: Of the 9004 isolates tested, 3232 (35.89%) were sensitive and 568 (6.31%) were resistant to all three combination agents, and rest 5204 (57.80%) were resistant to at least one of the combinations. Susceptibility to piperacillin/tazobactam, cefoperazone/sulbactam, and ticarcillin/clavulanic acid was 81.37, 76.06 and 45.48 per cent respectively. Piperacillin/tazobactam exhibited significantly (P<0.05) greater antimicrobial activity against Pseudomonas spp., Escherichia coli and Klebsiella spp. compared to cefoperazone/sulbactam. INTERPRETATION & CONCLUSION: Overall piperacillin/tazobactam was observed to be the best combination agent followed by cefoperazone/sulbactam in our setting. This difference in activities of these combination agents needs to be evaluated further by ascertaining their efficacy in clinical studies.

In vitro activity of ceftriaxone plus tazobactam against members of Enterobacteriaceae.

AIMS: To study the in vitro activity of ceftriaxone alone and in combination with the beta-lactamase inhibitor tazobactam against bacterial isolates belonging to the Family Enterobacteriaceae. METHODS: One hundred and five consecutive isolates of Escherichia coli and Klebsiella spp. that had been recovered from various high-risk areas of the hospital were included in the study. MIC estimation to ceftriaxone and a combination of ceftriaxone and tazobactam was performed by the agar dilution method. RESULTS: By the MIC studies, 88.6% of the strains appeared to be resistant to ceftriaxone with the MIC90 value being > 256 microg/ml. When the MIC were done to ceftriaxone in combination with tazobactam, the resistance rate dropped to 4.8% with the MIC90 value being 4.0 microg/ml. CONCLUSION: The combination of ceftriaxone and tazobactam appears to be an excellent therapeutic alternative with 94.6% of ceftriaxone resistant strains being susceptible in vitro to this combination.

Antibiotics in older adults

Antibiotics are frequently prescribed in the older person, the dosification needs special care, since the pharmacokinetic parameters changes with aging and the side effects can be different in the older person. The creatinine clearance changes and we must modify the way we prescribe such antibiotics to the elderly, calculating. The variety of antibiotics now available led us to consider this paper in which we have presented the antimicrobial agents that can be considered in the treatment of the older person. We present several groups: the penicillins, cephalosporins, monobactams, carbapenems and betalactamase inhibitors or the great betalactam group. Other trimetroprin-sulfame-thoxazole, the newer macrolides (azithromycin and clarithromycin) as well as the aminoglycosides, vancomycin, clindamycin, metroridazole. The indications and contraindications are presented and reviewed.

A preliminary study on metallo-beta-lactamase producing Pseudomonas aeruginosa in hospitalized patients.

Metallo beta-lactamase (MBL) producing Pseudomonas aeruginosa is an emerging threat and a cause of concern for the physicians treating such infections. The present study was undertaken to know the resistance pattern of P. aeruginosa to beta-lactamase inhibitors and carbapenems, and to detect the presence of MBL among resistant isolates to both groups of antibiotics. Between June-November 2001, 50 P. aeruginosa isolates from clinical specimens were tested for susceptibility to beta-lactamase inhibitors and carbapenems by Kirby-Bauer disc diffusion method. Isolates resistant to both groups of antibiotics were screened for the presence of MBLs by disc diffusion method using 2-mercaptoethanol. Of the 50 isolates, 6 (12%) were resistant to both beta-lactamase inhibitors and carbapenems. All 6 isolates were MBL producers were resistant to all the antibiotics tested. Resistance to piperacillin-tazobactam, cefoperazone-sulbactam and ticarcillin-clavulanic acid was 12, 20 and 36 per cent respectively. Resistance of 12 per cent each was noted to imipenem and meropenem respectively. This is to the best of our knowledge the first report of MBL producing P. aeruginosa from India and suggests the need for early detection, notification and control of spread.

Inactivación de ß-lactamasas por sulbactam en presencia de anticoagulante y en anaerobiosis / ß-lactamase inactivation by sulbactam in aerobiosis and anticoagulant

Se aislaron cepas de Staphylococcus aureus resistentes a penicilina y productoras de ß-lactamasas. Mediante el método de dilución en tubos, se calculó la concentración inhibitoria CIM para amoxicilina-sulbactam, con diferente tensión de oxígeno y frente a heparina. Los valores de CIM se redujeron significativamente al sumar sulbactam al antibiótico. La disminución del oxígeno no afectó la capacidad inhibidora de ß-lactamasas del sulbactam, del mismo modo que la presencia de heparina no interfirió en su efecto protector sobre la amoxicilina. Estos resultados reafirmaron el concepto de efectividad de la combinación amoxicilina-sulbactam sobre los procesos infecciosos a S. aureus productores de ß-lactamasas, aun en afecciones donde se genera anaerobiosis relativa y también en enfermos con tratamiento simultáneo con heparina

Unique metabolic properties of Mycobacterium leprae.

My first contact with Dr. Dharmendra was through correspondence. While working for Ph.D., I wrote to him that a section in his book "Notes on Leprosy" was ambiguous. Instead of ignoring the letter, he replied, agreeing to clarify it in the revised edition. I went to work at Carville at the invitation of Dr. Kirchheimer, who had seen my Ph.D. thesis. Dr. Dharmendra visited Carville to receive the Damien-Dutton award and stayed there for a few days. Carville is an isolated place with no public transportation. I used to take him for afternoon drives to the countryside around Carville. He published some of our papers in Leprosy in India and later in Indian Journal of Leprosy. He was very prompt in acknowledging receipt of manuscripts and suggesting any changes to be made. He also reprinted in the Journal several of our papers published elsewhere, and also a lecture I gave at a meeting of the Japanese Leprosy Association. During one of my visits to India, Dr. M. C. Vaidya had arranged a talk by me at the All India Institute of Medical Sciences, New Delhi. At the invitation of Dr. Dharmendra, I visited him in his home. We used to exchange new year cards and letters. He wrote to me about his eye infection and consequent loss of sight in one eye. He asked me to write an editorial for an issue of Indian Journal of Leprosy (January 1989). The last time I met him was during the International Leprosy Congress held in New Delhi.

Inibidores das beta-lactamases e seu uso clínico / Beta-lactamase inhibitors and its clinical use

Os autores fazem uma revisäo bibliográfica sobre as drogas inibidoras das beta-lactamases e abordam sua farmacologia e seu uso clínico atual, baseando-se na combinaçäo dos antimicrobianos e no próprio inibidor da beta-lacatamse. Há muito tempo é conhecido o fato de que germes gram positivos e germes gran negativos säo capazes de produzir enzimas de composiçäo química complexa denominadas beta-lactamases, as quais têm a propriedade de atuar sobre o anel beta-lactamases, beta-lactâmico (componente da estrutura química de alguns antimicrobianos) inativando-o e fazendo com que tais germes se tornem resistentes a estes antimicrobianos (3). Investigaçöes clínicas recentes levaram a descoberta de certas moléculas que podem se ligar de forma irreversível as beta-lactamases e inativá-las, impedindo assim a destruiçäo dos antimicrobianos beta-lactâmicos (3), fazendo com que drogas antigas como ampicilina, amoxacilina e ticarcilina passem a atuar, quando associadas a estas novas substâncias, sobre germes produtores de beta-lactamases, propiciando ao paciente ao mesmo tempo o acesso a uma terapia de custo menor e de menor toxicidade intrínseca. Os agentes inibidores das beta-lactamases têm propriedades, consideravelmente diferentes daquelas das penicilinas e cefalosporinas, assim como säo estruturalmente diferentes destas, tendo baixa atividade intrínseca sobre micoorganismos (4) quando isolados mas que acreditamos de grande valor terapêutico no futuro. Atualmente säo conhecidos dois agentes inibidores das beta-lactamases: o ácido clavulcânico e o sulbactam, os quais passaremos a abordar (5)