Klebsiella pneumoniae carbapenemase - Case Study Example

 Klebsiella pneumoniae carbapenemase Early in this decade, enterobacteriaceae which produce Klebsiella pneumoniae carbapenemase (KPC) were reported in the United States of America and subsequently in the entire globe. These KPC producing pathogens are predominantly involved systemic and nosocomial infections. Although they are most of the time enterobacteriaceae, they can at times be isolates from Pseudomonas aeruginosa. KPC lactamases confer reduced susceptibility or resistance to virtually all β lactams. Carbapenems such as meropenem, imipenem and ertapenem can therefore be inefficient in the treatment of such infections. These KPC-producing bacteria are in addition resistant to a vast range of other non-β-lactam molecules thus limiting the available therapeutic options. Detection of Klebsiella pneumoniae carbapenemase producing bacteria may be difficult on the basis of routine antibiotic susceptibility testing. Therefore, it is crucial to implement efficient infection control measures in order to minimize spread of the pathogens (Endimiani, Hujer, Perez, Bethel, Hujer, Kroeger, et al. 2009). In this particular case study, issues such as risk factors, treatment options, ICU procedures screening, mortality and transmission will be tackled. Klebsiella pneumoniae carbapenemase (KPC) is a molecular class A serine β-lactamase that belongs to the functional group 2. The first Klebsiella pneumoniae carbapenemase producing isolate was K pneumoniae from North Carolina, USA identified in 1996. This particular isolate of Klebsiella was resistant to all β-lactams, but carbapenem minimum inhibitory concentrations (MICs) were insignificantly reduced following the addition of clavunate, an inhibitor of β-lactamase (Nordmann, Cuzon & Naas, 2009). Risk factors The widespread dissemination of this organism which is tightly linked to its antimicrobial resistance means that KPC-kp is a dangerous pathogen. Specific virulence factors associated with Klebsiella pneumoniae carbapenemase producing bacteria have not been reported. Risk factors linked to KPC producing bacteria include intensive care unit (ICU) stay and prolonged hospitalization. In Europe and particularly in Greece, the European Antimicrobial Resistance Surveillance Network (EARSN) has been declared an endemic region with regard to KPC-relate infections. In the case study, the fifth patient was diagnosed with the pathogen 8 days prior to isolation. The patient’s stay at the ICU may have been a risk factor considering the first patient was also in the ICU. With this regard, this pathogen is also implicated has been implicated in most ICUs because it may occur as a nosocomial infection. Other factors are immunosuppression, invasive devices and multiple antibiotic agents before culture. The 73 year old patient immune system was immune compromised and as such immune suppression may have been a risk factor. This is because; the patient had undergone a kidney transplant then suffered colon perforation. Furthermore, the patient had been previously treated with various antibiotics which might have also exposed him to the dangerous pathogen (Poirel, Pitout, Nordmann, 2007). Early detection of the risk factors for hospital acquired infection, such as ICU stay, poor functional status and receipt of antibiotics has to be critically considered in controlling the spread (Endimiani, Hujer, Perez, Bethel, Hujer, Kroeger, et al. 2009). Treatment Studies involving antimicrobial treatment of KPC associated infections and clinical results are based on a minimal quantity of case patients. Consequently, the optimal treatment regimens have not been well established. In this respect, in vitro experiments assessing various antibiotic combinations are required. Susceptibility testing data shows that treatment of KPC infections caused by KPC pathogens commonly requires use of colistin or tigecycline as the last resort drugs. The 73 year old patient was treated with this combination of antibiotics as the last option. Although the regimen was sensitive, the patient was unable to survive despite the broad spectrum of these antibiotics. In some cases, meropenem also has the ability to retain the phenotypic activity of KPC producers and is considered as an alternative. Tigecycline, a glycylcycline antibiotic is used in treatment of skin and complicated intra abdominal infections. Nonetheless, this antibiotic has found importance in the treatment of enterobacteriaceae regardless of the presence of carbapenemases. Its mode of action is the inhibition of bacterial protein synthesis and is mostly bacteriostatic. Neither the expanded spectrum of cephalosporins and carbapenems can be used in systemic treatment of KPC associated infections. During meropenem and imipenem therapy, high level carbapenem resistant KPC producing bacteria may be selected. This may have been the consequence of the health department not screening for gram-negative bacteria. Such bacteria are the major causes of multidrug resistance especially in ICU (Lee & Burgess, 2012). KPC producing isolates are usually resistant to many non β-lactam molecules including co-trimoxazole, fluoroquinolones and aminoglycosides. In this case, the patient had undergone almost similar antibiotic regimen but treatment with the set failed. This is mainly attributed to resistance to these non-beta lactams. A majority of KPC producing bacteria produce other β lactamases which are resistant to inhibitors of cephalosporinases. This automatically rules out the use of clavunate as an inhibitor in combination with beta lactam in the treatment of systemic infections (Papadimitriou-Olivgeris, Marangos, Fligou, Christofidou, Bartzavali, Anastassiou, et al. 2012). Transmission The spread of KPC-kp is an increasing challenge posing serious obstacles in treatment options and resulting in frequent clinical failure in intensive care units (ICUs). A small yet significant percentage of all the intensive care unit patients show enteric colonization with the KPC-kp upon admission. Enteric colonization may have been the cause of death for patient number two. Other factors include previous hospitalization, use of carbapenems or beta lactams/beta lactamase inhibitors and COPD such as malignancies and renal or heart failure. In healthcare settings, intensive care units are the main pools of Gram-negative multidrug resistant bacteria. As such, the ICUs, present adequate opportunities for cross-transmission among patients. It is within this aspect that there was transmission to other three patients. The period of previous hospitalization has also been studied. It has been reported that the duration of previous hospitalization is markedly longer among colonized patients compared to non-colonized patients. It can be postulated that a longer hospital stay in the peripheral ward prior to ICU admission leads to cross transmission. This was the case in patient number five, who had a longer stay at the hospital before admission to the ICU. Co morbidities as exemplified by renal or heart failure can be an independent infection and colonization risk factor in ICUs (Pournaras, Vrioni, Neou, Dendrinos, Dimitroulia, Poulou, et al. 2011). Screening To effectively identify the extent of intestinal colonization among patients, active surveillance of cultures collected from the intensive care units has to be of utmost priority. Furthermore, infection control measures have to be adhered to at all times in such sensitive clinical areas. However, because this was the first outbreak, the control measures may have been compromised. Such interventions are exemplified by formulating and following the contact precautions. The staff should have minimal contacts to the infected patients to avoid cross transmission. Additionally, there should be isolation of patients who are infected with the KPC-kp strains as well as employing very dedicated staff personnel. The use of up to date modern efficient equipment should also be used in order to control infection with carbapenem-resistant pathogens in acute care facilities. The detection of Klebsiella pneumoniae carbapenem producing bacteria solely on the basis of susceptibility testing is not simple. This task is not easy because of the heterogeneous expression of the beta lactam resistance. In order to fully express the carbapenem resistance characteristic, an additional mechanism such as outer membrane permeability defect may be required (Yigit, Queenan, Anderson, et al. (2001). Testing through agar diffusion also has inconsistencies. Generally, susceptibility testing via imipenem or meropenem is not sensitive enough in the detection of KPC producing enterobacteriaceae. Susceptibility testing through the Etest technique poses challenges in interpretation of outcome. The scattered colonies can form inhibition segments which are difficult to read especially for Klebsiella pneumoniae. The hidden spread of KPC producing bacteria may be associated to the failure to determine these strains in samples. Additionally, this effect may lead to failure in identification of patients whose gastrointestinal tracts are asymptomatically colonized. In endemic and pandemic areas, targeted surveillance is mandatory in detecting gastrointestinal colonization among patients. This is because KPC producing bacteria have an environmental source (Tenover, Kalsi, Williams, et al. (2006). Detection of carriers of KPC forming bacteria has been proposed by the screening of faecal flora with a plating procedure and screening using imipenem containing disks. The Chromagar KPC, a novel chromagenic media has a high specificity an sensitivity compared to PCR. This technique shows a vast avenue or improving KPC screening. An alternate method that can be employed in screening of KPC producing bacteria is the ready to use chromic ESBL medium or isolation of ESBLs. This screening intervention is useful in the detection of KPC producing bacteria in areas outside the endemic regions. A number of confirmatory tests have been put forward. The results of double-disc synergy testing between tazobactam and clavulanic acid and any carbapenem are difficult to detect due to low inhibition of KPC especially by clavunate. In such eventualities, the modified Hodge test may be helpful in determining the carbapenemase although it doesn’t exclusively shoe the KPC type (Hirsch & Tam, 2010). Identification of Klebsiella pneumoniae carbapenem producing bacterial pathogens with molecular tools should ideally be the gold standard. Quite a number of polymerase chain reactions (PCRs) have been improvised using either real time or endpoint techniques for clinical and clone samples. The pathogen causing drug resistance was detected via PCR and so the health centre was well equipped with such resources. Probably, the screening should be more focused within the ICU because it was the hub for the pathogen. Although, these techniques are more specific, they do require technical expertise. Furthermore, such strategies require modern equipment such a as sequencers which are mostly costly. Therefore, their regular use should depend on the rate of KPC forming bacteria. Alternatively, molecular confirmation assays can be restricted to designated reference laboratories (Birgy, Bidet, Genel, Doit, Decré, Arlet, et al. 2012). 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