Carbapenem Resistance in Klebsiella pneumoniae Due to the New Delhi Metallo- -lactamase

Sidjabat, Hanna E.; Nimmo, Graeme R.; Walsh, Timothy R.; Binotto, Enzo; Htin, Anthony; Hayashi, Yoshihiko; Li, Jian; Nation, Roger L.; George, Narelle; Paterson, David L.

doi:10.1093/cid/ciq178

Cited by 117 publications

(99 citation statements)

References 30 publications

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“…Due to the prevalence of multidrug-resistant bacteria, especially the emergence of superbugs (46,47), there is an urgent need for novel therapeutic agents that are directed against such pathogens. Phage lysin (48) and the natural products derived from traditional Chinese medicine (49) are considered novel therapeutic agents because their mechanism of action is different from that of antibiotics.…”

Section: Figmentioning

confidence: 99%

Combination Therapy of LysGH15 and Apigenin as a New Strategy for Treating Pneumonia Caused by Staphylococcus aureus

Xia

Wang

et al. 2016

Appl Environ Microbiol

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c Pneumonia is one of the most prevalent Staphylococcus aureus-mediated diseases, and the treatment of this infection is becoming challenging due to the emergence of multidrug-resistant S. aureus, especially methicillin-resistant S. aureus (MRSA) strains. It has been reported that LysGH15, the lysin derived from phage GH15, displays high efficiency and a broad lytic spectrum against MRSA and that apigenin can markedly diminish the alpha-hemolysin of S. aureus. In this study, the combination therapy of LysGH15 and apigenin was evaluated in vitro and in a mouse S. aureus pneumonia model. No mutual adverse influence was detected between LysGH15 and apigenin in vitro. In animal experiments, the combination therapy showed a more effective treatment effect than LysGH15 or apigenin monotherapy (P < 0.05). The bacterial load in the lungs of mice administered the combination therapy was 1.5 log units within 24 h after challenge, whereas the loads in unprotected mice or mice treated with apigenin or LysGH15 alone were 10.2, 4.7, and 2.6 log units, respectively. The combination therapy group showed the best health status, the lowest ratio of wet tissue to dry tissue of the lungs, the smallest amount of total protein and cells in the lung, the fewest pathological manifestations, and the lowest cytokine level compared with the other groups (P < 0.05). With regard to its better protective efficacy, the combination therapy of LysGH15 and apigenin exhibits therapeutic potential for treating pneumonia caused by MRSA. This paper reports the combination therapy of lysin and natural products derived from traditional Chinese medicine. Staphylococcus aureus is a ubiquitous and zoonotic pathogen that causes high morbidity and mortality in a variety of diseases, ranging from skin and soft tissue infections to necrotizing pneumonia and overwhelming sepsis (1, 2). S. aureus pneumonia is one of the most prevalent S. aureus-mediated diseases and accounts for 13.3% of all invasive S. aureus infections (3). Treatment of S. aureus infection has become increasingly difficult, given the prevalence of multidrug-resistant S. aureus strains, especially the widespread existence of methicillin-resistant S. aureus (MRSA) strains (4). MRSA strains are typically resistant to multiple antibiotics, including gentamicin, erythromycin, fluoroquinolones, and ofloxacin, among others (5). There are also reports of vancomycin-resistant S. aureus (VRSA), raising serious concerns within the medical community (6-8). Therefore, there is an urgent need for novel therapeutic strategies that are efficient against this pathogen.Lysin, which is encoded by the phage (bacterial virus) genome at the end of the phage lytic life cycle to lyse the host cell, can rapidly and specifically lyse Gram-positive bacteria when exogenously applied (9). Because the bacterial cell wall is conserved and necessary for the life cycle, the current lack of bacterial resistance against lysin is not surprising (10). In addition, its species specificity or type specificity ensures that lysin w...

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Section: Figmentioning

confidence: 99%

Combination Therapy of LysGH15 and Apigenin as a New Strategy for Treating Pneumonia Caused by Staphylococcus aureus

Xia

Wang

et al. 2016

Appl Environ Microbiol

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“…Previously, K. pneumoniae strains of ST types 14 (Yong et al, 2009;Poirel et al, 2011;Mulvey et al, 2011), 16 (Mulvey et al, 2011), 340 (Poirel et al, 2011) and 147 (Sidjabat et al, 2011) have been shown to carry NDM-1, all of them unrelated to ST231. Only information about six ST231 K. pneumoniae isolates is available at the Institut Pasteur MLST database (http://www.pasteur.fr/recherche/genopole/PF8/mlst/ Kpneumoniae.html; last accessed January 2012), four of them isolated from Vietnam (two meningitis and one sepsis), one from Africa (urinary tract infection) and one from India (peritoneal fluid).…”

Section: Resultsmentioning

confidence: 99%

Abdominal abscess due to NDM-1-producing Klebsiella pneumoniae in Spain

Oteo

Domingo-García

Fernández-Romero

et al. 2012

Journal of Medical Microbiology

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We describe a clinical case of an abdominal abscess due to NDM-1-producing Klebsiella pneumoniae in a 35-year-old Spanish patient after hospitalization in India for perforated appendicitis and peritonitis. The strain belonged to the MLST type 231 and had multiple additional antibiotic resistance genes such as bla CTX-M-15 , armA methylase, aac(69)-Ib-cr, dfrA12, sul1 and qnrB and lack of porin genes ompK35 and ompK36. The patient was cured after abscess drainage. IntroductionAcquired carbapenemases are increasingly reported in Gram-negative pathogens (Miriagou et al., 2010). Metallob-lactamases belong to the class B carbapenemases and confer resistance to all b-lactams, including carbapenems, except aztreonam. Spread of metallo-b-lactamases among members of the Enterobacteriaceae represents a public health threat. Although VIM and KPC types are the most common carbapenemases in Europe, the class D OXA-48 carbapenemase is also spreading, and the New Delhi metallo-blactamase 1 (NDM-1) has been described in Sweden (Yong et al., 2009) We describe a clinical case of NDM-1-producing Klebsiella pneumoniae in Spain causing an abdominal abscess after surgery for perforated appendicitis. To the best of our knowledge, this is the first case of NDM-1-producing K. pneumoniae in our country. Case reportA 35-year-old white male was admitted to a third level teaching hospital in Madrid (Spain) in August of 2010 due to acute abdominal pain in the right iliac fossa. In the previous 9 days, the patient had been hospitalized in India because of acute perforating appendicitis followed by peritonitis. The patient underwent a laparoscopic appendectomy and peritoneal cavity washing. Pseudomonas aeruginosa and Escherichia coli were cultured from the peritoneal fluid, both susceptible to levofloxacin and meropenem, and treatment with one unidentified antibiotic was prescribed for 5 days.The patient returned to Spain, and 2 days after completing antibiotic treatment started to have pain in the right iliac fossa and had a temperature of 38.8 u C. A haemogram revealed leukocytosis and an abdominal echography showed a pus collection in the right iliac fossa. Blood cultures were obtained, and antimicrobial therapy with amoxicillin/ clavulanic acid (1 g t.i.d.) was prescribed. Three days later, leukocytosis continued, treatment was changed to meropenem (1 g t.i.d.) and the abscess was then drained. The purulent exudate was cultured onto conventional media for aerobic and anaerobic bacteria following standard methodologies. Growth was positive for Enterococcus faecium and carbapenem-resistant K. pneumoniae but anaerobic cultures were negative. Blood cultures were also negative.Although the patient was not specifically treated with antibiotics active against carbapenem-resistant K. pneumoniae, his health condition improved over the next 2 weeks, probably due to the pus drainage. A control echography did not reveal any pus collection and the patient was discharged 16 days after pus drainage. No secondary clinical cases were observed. MethodsAn...

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“…Another case was reported from an 87-year-old woman, who had clinical signs, for example, fever, dysuria and suprapubic pain. Urine culture produces a positive result for Klebsiella pneumoniae and E. coli, both resistant to multiple antibiotics including β-lactams [32]. β-lactam resistance can be seen in serious infections such as cystic ibrosis.…”

Section: Speciic Cases Of Resistance To β-Lactam Antibioticsmentioning

confidence: 99%

Toxicity of β-Lactam Antibiotics: Pathophysiology, Molecular Biology and Possible Recovery Strategies

Bozcal¹,

Dagdeviren²

2017

Poisoning - From Specific Toxic Agents to Novel Rapid and Simplified Techniques for Analysis

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Beta (β)-lactam antibiotics are wide-spectrum antibiotics used for various bacterial infections. The aim of this chapter is to summarize the knowledge about the toxicity of β-lactam antibiotics and issues associated to their inappropriate use. This review has highlighted that β-lactam antibiotics are a group of products that have a chemical structure characterized by a β-lactam ring and are one of the most common antibacterial agents. However, due to the inappropriate use including abuse and misuse, resistance to the β-lactam antibiotics is currently a global crisis. Moreover, even when used appropriately, they have been linked to triggering allergic reactions like urticaria, bronchoconstriction, also severe conditions like immune-mediated haemolytic anaemia and intravascular haemolysis. It is known that some β-lactam antibiotics are neurotoxic, some are nephrotoxic, some are genotoxic and some are toxic to urogenital system. Several factors are involved in the occurrence of toxic efects including the dosage and renal status. Several strategies are possible to overcome β-lactam antibiotics-triggered toxicity, including rational prescribing, substitution combination and phage therapy which seems promising. Public health education for clinical teams and patients is essential in ensuring that this group of antibiotics are retained in therapeutics.

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Carbapenem Resistance in Klebsiella pneumoniae Due to the New Delhi Metallo- -lactamase

Cited by 117 publications

References 30 publications

Combination Therapy of LysGH15 and Apigenin as a New Strategy for Treating Pneumonia Caused by Staphylococcus aureus

Combination Therapy of LysGH15 and Apigenin as a New Strategy for Treating Pneumonia Caused by Staphylococcus aureus

Abdominal abscess due to NDM-1-producing Klebsiella pneumoniae in Spain

Toxicity of β-Lactam Antibiotics: Pathophysiology, Molecular Biology and Possible Recovery Strategies

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