Hippocrates: A Pioneer in Orthopaedics and Traumatology.

PURPOSE: Hippocrates, the ancient Greek physician, is considered the father of Medicine; however, his contributions to Orthopaedics and Traumatology have not been highlighted enough. The present historical review represents an effort to present and categorize his work, in this field, per clinical disorder and anatomical region. METHODS: The "Hippocratic Corpus" original text was thoroughly studied to identify all Hippocrates' contributions in Orthopaedics and Traumatology. Volume III of his works, especially "On Fractures", "On Joints", and "Mochlicon" includes a plethora of information regarding the management of traumas, as well as other disorders and clinical entities of the musculoskeletal system. RESULTS: In particular, Hippocrates describes reduction techniques for fractures, as well as joint dislocations, elaborates on the biology of the fractures' healing process and the basic principles of fracture management and fixation, presents the signs and symptoms of gangrene, teaches the treatment of osseous infections and offers valuable insight on the biomechanics and treatment of spinal diseases. CONCLUSIONS: Hippocrates' contributions in Orthopaedics and Traumatology are unprecedented, making him a true pioneer in this field, while the basic principles that he presented were further studied and confirmed in the 19th and 20th centuries.

Late-onset spondylodiscitis and psoas abscess, 5 years after percutaneous balloon kyphoplasty: a case report.

Postoperative infection following percutaneous balloon kyphoplasty (PBK) is a rare complication and delayed onset infection is very rare. We report the case of a 62-year-old male, who developed spondylodiscitis and psoas abscess 5 years after two-level, L2 and L3 PBK. He was initially treated with abscess aspiration and long term antimicrobial treatment. Eventually, due to failure of conservative treatment he underwent anterior decompression, radical debridement of the infected tissue and non-instrumented fusion with strut graft, with excellent results.

C1q Gene Polymorphism Is Associated with Asymptomatic Bacteriuria in Patients with Type 2 Diabetes Mellitus.

Background and Objectives: Asymptomatic bacteriuria (ASB) appears to have a higher prevalence in diabetics and has been associated with various genetic polymorphisms of the innate immune system. Single nucleotide polymorphisms (SNPs) of the C1q gene that encodes for the trigger molecule of the classical complement pathway increase the risk of bacterial infections as well as other diseases. In the present study, we sought to investigate the association of C1q rs292001 (G > A) SNP with ASB in patients with type 2 diabetes (T2D). Materials and Methods: In this case-control study, performed at the University and the Venizeleion General Hospital of Heraklion, Crete, Greece, 75 adult male and female Cretan patients with T2D and ASB and 75 adult male and female Cretan patients with T2D but without ASB were enrolled and genotyped for rs292001 SNP of C1q gene. Genetic analysis was based on the polymerase chain reaction (PCR) and restriction fragment length polymorphisms (RLFPs) methods. Results: Τhe frequency of homozygotes for the G/G genotype of C1q rs292001 was significantly higher in patients with T2D and ASB than in the control group (p-value = 0.0480, OR = 2.952, 95% CI: 1.052−7.542). Conclusions: Τhe present study provides the first evidence of an association between the C1q rs292001 SNP and an increased susceptibility for ASB in an adult Cretan population with T2D, thus suggesting that this SNP can be encountered as a risk factor for the presence of ASB in patients with T2D.

Theophrastus Bombastus Von Hohenheim: Theological Reformer, Philosopher and Physician.

Theophrastus Bombastus Von Hohenheim (1493-1541), known as Paracelsus, was a German-Swiss Renaissance man. His interests included alchemy and medicine. During the early 1500s, he worked as a physician, introducing mineral-based therapies to treat ailments. He is credited with developing the first recipe for laudanum, a powerful opium-based pain medication. He had radical beliefs, claiming that supreme knowledge could be reached by observing nature, not by reading books. He expressed rebellious opinions on religious topics and, though devoted Christian, criticized the Catholic Church, preaching that the spirit of Christianity dwells in the human soul and not within the church walls. Paracelsus' efforts to "renovate" the expression of the Christian faith by limiting the ritual and augmenting the spirituality among believers are presented.

Treatment pattern, prognostic factors, and outcome in patients with infection due to pan-drug-resistant gram-negative bacteria.

The present study investigated the clinical course, treatment pattern, prognostic factors, and outcome of patients with pun-drug resistant (PDR) infections. This was a retrospective single-center cohort study including consecutive eligible patients with a PDR infection hospitalized at the University Hospital of Heraklion, Crete, Greece, between January 2010 and June 2018. In total, 65 patients with infections due to PDR gram-negative pathogens were identified. The median age was 64 years (interquartile range, IQR: 45.5-74.5) and the median Charlson comorbidity index 3.0 (IQR: 1.0-5.75). Of the 65 PDR isolates, 31 (48%) were Klebsiella pneumoniae, 28 (43%) Acinetobacter baumannii, and 6 (9%) Pseudomonas aeruginosa. The most common empirical therapy was colistin-based combination (n = 32; 49%), followed by non-colistin, non-tigecycline combination (n = 25; 39%), and carbapenemes + tigecycline (n = 8; 12%). The empirical therapy was effective in 50%, 37.5%, and 8% of patients receiving colistin combination, carbapenemes - tigecycline, and non-colistin, non-tigecycline combination, respectively (p value = 0.003). The infection-related in-hospital mortality was 32% (95% confidence interval, CI: 21-45%). Three factors were significantly associated with infection-related in-hospital mortality in multivariate analysis: Charlson comorbidity index (odds ratio, OR: 1.5, 95% CI: 1.0-2.3, p value = 0.030), prior steroid use (OR: 4.1, 95% CI: 1.0-17.0, p value = 0.049), and empirical treatment with non-colistin, non-tigecycline combination (OR: 7.5; 95% CI: 1.7-32.8, p value = 0.008). Infections due to PDR pathogens are associated with considerable mortality. Our results support the use of colistin and/or tigecycline-based combinations as empirical therapy when infection due to PDR pathogens is suspected.

Hospital-wide antifungal prescription in Greek hospitals: a multicenter repeated point-prevalence study.

The aim of the study was to evaluate antifungal prescriptions among hospitalized adult patients in Greek hospitals. This multicenter two-times, 1-day, point-prevalence study was carried out in 2015 and 2017 in five and six hospitals, respectively. Among the 5812 patients screened in both periods, antifungals were prescribed in 129 patients (73 in 2015 and 56 in 2017); antifungals were used as prophylaxis in 31 patients (24%), pre-emptively in 32 (25%), empirically in 38 (30%), and as targeted therapy in 28 (22%). Triazoles were the class most commonly used (65 patients; 50%), followed by echinocandins (59; 46%) and liposomal amphotericin B (12; 9%). The use of echinocandins was higher (P 0.009) in the ICU (16 out of 22 patients), as compared with those in other departments (40%). Antifungal treatment was deemed inappropriate in 32/129 patients (25%) (16% in 2015 versus 36% in 2017; P 0.014). Inappropriate antifungal administration was more common if indicated by the primary physician, as compared with an infectious disease specialist (35% versus 5%; P < 0.001). Candidemia represented the majority of microbiologically documented infections (12 out of 28). Only two cases of proven pulmonary aspergillosis were diagnosed. Fluconazole and echinocandins were most frequently prescribed for identified or presumptive fungal infections, while fluconazole or posaconazole was given most frequently as prophylaxis. Antifungal treatment has been, ultimately, proven unnecessary in one-fourth of cases, underlining the need of a nationwide antifungal stewardship program.

Rhodotorula species infections in humans: A systematic review.

BACKGROUND: Fungal infections by Rhodotorula species are increasingly reported in the literature and consist of bloodstream infections, especially in patients with central venous catheters (CVC), as well as central nervous system (CNS), ocular and other less frequent infections. OBJECTIVES: The aim of this systematic review was to record and evaluate all available evidence regarding infections by Rhodotorula species. METHODS: Systematic review of PubMed (through 9 August 2017) for studies providing epidemiological, clinical, microbiological, as well as treatment data and outcomes of Rhodotorula species infections. RESULTS: A total of 111 studies, containing data of 248 patients, were eventually included in the analysis. The most common Rhodotorula infections were those of bloodstream, CNS and ocular infections, as well as peritoneal dialysis-associated peritonitis. Epidemiology of each type of infection was different, with the bloodstream ones being more common in patients with malignancy and CVCs, while those of the CNS were more common in patients with AIDS. Mortality was variable being higher in CNS infections. Amphotericin B remains the most common agent used for treatment, irrespectively of the infection site. CONCLUSIONS: This systematic review thoroughly describes fungal infections by Rhodotorula species and provides information on their epidemiology, clinical picture, microbiology, treatment and outcomes.

Candida glabrata prosthetic joint infection, successfully treated with anidulafungin: A case report and review of the literature.

Non-albicans Candida prosthetic joint infection (PJI) is extremely rare. A case of a Candida glabrata knee PJI is a 68-year-old splenectomised female smoker, suffering from chronic obstructive pulmonary disease (COPD) and alcoholism is reported. The patient presented with a peri-prosthetic fracture, 15 years after total knee replacement surgery. Cultures of the intraoperative peri-prosthetic tissue and materials yielded C. glabrata, as well as a methicillin-resistant S. epidermitis. The patient was treated with anidulafungin and vancomycin. The knee prosthetic joint was removed and cement-spacer with vancomycin and gentamycin was placed. Additionally, an external fixation was performed. A second stage revision surgery was planned, after completion of the antimicrobial and antifungal treatment. The patient is followed up for 4 months without signs, symptoms or findings of infection. PJI Candida infections require a high clinical suspicion index. It is of utmost importance to report these cases, since there is no consensus yet of the proper antifungal treatment. Furthermore, a literature review regarding treatment of those cases is provided. First-line treatment with an echinocandin seems most proper, due to their fungicidal properties, their effectiveness against biofilm, as well as their minimal toxicity, making them ideal for long-term use. Further experience is needed, for better understanding the disease's pathogenesis and optimal treatment.

Machaon: the first trauma surgeon in Western history?

Homer's epics, the Iliad and the Odyssey, written between 800-700 BC, offer valuable information about what medical practice meant at that time. Descriptions of injuries and care given can be found among the 26,000 verses of these poems. During the Trojan War many warriors possessed empirical knowledge of wound care. However, Machaon and his brother Podalirius were the chief medical officers of the Greek army as it besieged Troy. Machaon was acting mainly as a trauma surgeon, while Podalirius was a physician. The original texts of the Iliad and Odyssey, as well as relevant literature and references, were methodically studied for extraction of adequate information about the life and work of Machaon. He provided medical care to injured soldiers and officers, and performed small operations. He treated the wound of King Menelaus of Sparta, the co-chief of the Greek army and many others. He was also a talented warrior, participating in many battles around the walls of Troy. When he was injured, the Greeks rallied around him so that he would not be taken or killed by the enemy. Since he had the knowledge and the ability to save lives, his life was considered equal to that of many men. Future generations would worship him as god protector of surgery. Machaon's techniques and skills can be considered to constitute the origins of modern surgery and trauma management at the dawn of western civilisation.

Fosfomycin.

The treatment of bacterial infections suffers from two major problems: spread of multidrug-resistant (MDR) or extensively drug-resistant (XDR) pathogens and lack of development of new antibiotics active against such MDR and XDR bacteria. As a result, physicians have turned to older antibiotics, such as polymyxins, tetracyclines, and aminoglycosides. Lately, due to development of resistance to these agents, fosfomycin has gained attention, as it has remained active against both Gram-positive and Gram-negative MDR and XDR bacteria. New data of higher quality have become available, and several issues were clarified further. In this review, we summarize the available fosfomycin data regarding pharmacokinetic and pharmacodynamic properties, the in vitro activity against susceptible and antibiotic-resistant bacteria, mechanisms of resistance and development of resistance during treatment, synergy and antagonism with other antibiotics, clinical effectiveness, and adverse events. Issues that need to be studied further are also discussed.

Factors Influencing Non-albicans Candidemia: A Case-Case-Control Study.

The study identified factors predisposing to non-albicans candidemia with special interest to prior antimicrobial treatment. A retrospective, case-case-control study was performed at the University Hospital of Heraklion, Greece, from November 2007 through September 2011 including adult patients. The study had three groups. The first included 58 patients with non-albicans candidemia, the second 48 with C. albicans candidemia, while the third (control) 104 without candidemia. Each of the two candidemia groups was compared with the control using multivariate logistic regression model. The mean (SD) age of the non-albicans, the albicans and the control patients was 67 (12), 67 (18) and 59 (19) years, respectively. The most common non-albicans Candida spp. isolated were C. parapsilosis in 19 patients (33%), C. glabrata in 17 (29%) and C. tropicalis in 15 (26%). Independent risk factors for non-albicans candidemia were prior treatment with quinolones (p < 0.001), b-lactam-b-lactamase inhibitors (p = 0.011) and presence of central venous catheter (p = 0.05), while for C. albicans candidemia were prior treatment with quinolones (p < 0.001), carbapenems (p = 0.003) along with cardiac disease (p < 0.001). Neither duration of hospitalization nor in-hospital mortality [41% for the non-albicans vs 29% for C. albicans group (p = 0.192)] was significantly different between the two candidemia groups. The study reveals the role of antimicrobial exposure as a risk factor for candidemia caused by different species. Prior treatment with b-lactam-b-lactamase inhibitors was associated with non-albicans, while with carbapenems with C. albicans candidemia. Prior use of quinolones was associated with candidemia in general.

Trauma management in Homer's Iliad.

Homer's Iliad is one of the highest intellectual products of the early ancient Greek civilisation. A plethora of medical information lies within Iliad's 24 rhapsodies, and a total of 147 injuries are described. The present study records and evaluates all cases of trauma management included in this epic poem. Not only Iliad's original text but also all myths related to Iliad from the five-volume Greek Mythology by Ioannis Kakridis were meticulously studied to locate the injured person, the type of trauma, the care provider and the type of given care as well as the outcome of each case. A total of 21 cases were found and evaluated with a 5% mortality rate. The majority of these injuries were caused by an arrow (43%) and were located to the upper extremity (43%). Injuries of the head, neck and trunk were not treated as all of them were lethal. Many of the recorded trauma management techniques can be correlated to modern medicine. Furthermore, the role and skills of military doctors and paramedics, mentioned by Homer, is discussed.

Albumin Enhances Caspofungin Activity against Aspergillus Species by Facilitating Drug Delivery to Germinating Hyphae.

The modest in vitro activity of echinocandins against Aspergillus implies that host-related factors augment the action of these antifungal agents in vivo. We found that, in contrast to the other antifungal agents (voriconazole, amphotericin B) tested, caspofungin exhibited a profound increase in activity against various Aspergillus species under conditions of cell culture growth, as evidenced by a ≥4-fold decrease in minimum effective concentrations (MECs) (P = 0. 0005). Importantly, the enhanced activity of caspofungin against Aspergillus spp. under cell culture conditions was strictly dependent on serum albumin and was not observed with the other two echinocandins, micafungin and anidulafungin. Of interest, fluorescently labeled albumin bound preferentially on the surface of germinating Aspergillus hyphae, and this interaction was further enhanced upon treatment with caspofungin. In addition, supplementation of cell culture medium with albumin resulted in a significant, 5-fold increase in association of fluorescently labeled caspofungin with Aspergillus hyphae (P < 0.0001). Collectively, we found a novel synergistic interaction between albumin and caspofungin, with albumin acting as a potential carrier molecule to facilitate antifungal drug delivery to Aspergillus hyphae.

The role of aerosolized colistin in the treatment of ventilator-associated pneumonia: a systematic review and metaanalysis.

OBJECTIVES: The present meta-analysis and systematic review evaluated the efficacy and safety of aerosolized colistin as adjunctive therapy to i.v. antimicrobials or as monotherapy in the treatment of ventilator-associated pneumonia. DESIGN: The databases of MEDLINE and Cochrane Library up to June 2013 and all reference lists of the included studies and relevant reviews were searched. Studies were eligible if the efficacy and safety of aerosolized colistin in the treatment of ventilator-associated pneumonia was evaluated. An overall effect estimate for all dichotomous data as an odds ratio with 95% CI was calculated by the Mantel-Haenszel or the DerSimonian and Laird method depending on the statistical heterogeneity. The Grading of Recommendations Assessment, Development, and Evaluation approach was used to interpret the findings. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Sixteen studies fulfilled the inclusion criteria: eight were comparing adjunctive aerosolized versus i.v. colistin (seven observational cohort or case-control studies and one randomized trial) and were meta-analyzed, and eight were single arm and were only systematically reviewed. The Grading of Recommendations Assessment, Development, and Evaluation approach showed limitations of the study design and presence of inconsistency in most of the outcomes, but no obvious indirectness or imprecision of results reporting. Based on the above assessments, the quality of evidence presented for each outcome ranged from "very low" to "low." A significant improvement in clinical response (odds ratio, 1.57; 95% CI, 1.14-2.15; p = 0.006; I2 = 37%), microbiological eradication (odds ratio, 1.61; 95% CI, 1.11-2.35; p = 0.01; I2 = 0%), and infection-related mortality (odds ratio, 0.58; 95% CI, 0.34-0.96; p = 0.04; I2 = 46%) was observed with the addition of aerosolized colistin to i.v. treatment, whereas the addition of aerosolized colistin did not affect overall mortality (odds ratio, 0.74; 95% CI, 0.54-1.01; p = 0.06; I2 = 25%) or nephrotoxicity (odds ratio, 1.18; 95% CI, 0.76-1.83; p = 0.45; I2 = 0%). CONCLUSION: Based on the present results and awaiting further evidence from randomized trials, aerosolized colistin is associated with improved outcome in the treatment of ventilator-associated pneumonia although the level of evidence was low.

Study on the comparative activity of echinocandins on murine gut colonization by Candida albicans.

Colonization of the gastrointestinal (GI) tract by Candida species is a principal pathogenetic event for development of invasive candidiasis. Importantly, the effect of echinocandins, the preferred antifungal agents for treatment of invasive candidiasis, on GI tract colonization by Candida spp. is currently unknown. Herein, we used an established model of persistent murine GI tract colonization by Candida albicans to test the ability of different echinocandins to eradicate the yeast from murine gut. Adult male Crl:CD1 (ICR) BR mice were fed with chow containing C. albicans and subsequently treated with different echinocandins or normal saline via daily intraperitoneal injections for 10 days. Quantitative stool cultures were performed immediately before (week one), and weekly for three months after discontinuation of treatment. Notably, treatment with all three echinocandins used (caspofungin, anidulafungin, and micafungin) resulted in eradication of Candida albicans from the stools, as evidenced by the significant reduction of yeast cells from a mean of 4.2 log10 CFU/g of stool before treatment (week one of colonization) to undetectable (<2 log10 CFU/g of stool) levels (week 12, P < 0.0001). In contrast, there was no significant reduction of Candida yeast cells in the stools of control mice. Collectively, the ability of echinocandins to eradicate C. albicans from the stools could have important implications in prophylaxis of high-risk patients for development of invasive candidiasis originating from the GI tract.

Corticosteroids block autophagy protein recruitment in Aspergillus fumigatus phagosomes via targeting dectin-1/Syk kinase signaling.

Aspergillus fumigatus is the predominant airborne fungal pathogen in immunocompromised patients. Genetic defects in NADPH oxidase (chronic granulomatous disease [CGD]) and corticosteroid-induced immunosupression lead to impaired killing of A. fumigatus and unique susceptibility to invasive aspergillosis via incompletely characterized mechanisms. Recent studies link TLR activation with phagosome maturation via the engagement of autophagy proteins. In this study, we found that infection of human monocytes with A. fumigatus spores triggered selective recruitment of the autophagy protein LC3 II in phagosomes upon fungal cell wall swelling. This response was induced by surface exposure of immunostimulatory ß-glucans and was mediated by activation of the Dectin-1 receptor. LC3 II recruitment in A. fumigatus phagosomes required spleen tyrosine kinase (Syk) kinase-dependent production of reactive oxygen species and was nearly absent in monocytes of patients with CGD. This pathway was important for control of intracellular fungal growth, as silencing of Atg5 resulted in impaired phagosome maturation and killing of A. fumigatus. In vivo and ex vivo administration of corticosteroids blocked LC3 II recruitment in A. fumigatus phagosomes via rapid inhibition of phosphorylation of Src and Syk kinases and downstream production of reactive oxygen species. Our studies link Dectin-1/Syk kinase signaling with autophagy-dependent maturation of A. fumigatus phagosomes and uncover a potential mechanism for development of invasive aspergillosis in the setting of CGD and corticosteroid-induced immunosupression.

Anidulafungin versus caspofungin in a mouse model of candidiasis caused by anidulafungin-susceptible Candida parapsilosis isolates with different degrees of caspofungin susceptibility.

Candida parapsilosis isolates occasionally display resistance in vitro to echinocandins and cause breakthrough infections to echinocandins. The degree of the in vivo cross-resistance among echinocandins and the fitness loss associated with caspofungin (CAS) resistance of C. parapsilosis are not well studied. We compared the activities of CAS and anidulafungin (ANF), each given at 2 dosing schedules (high dose or low dose) in a nonneutropenic mouse model of invasive candidiasis (IC) caused by ANF-susceptible isolates of C. parapsilosis with different degrees of susceptibility to CAS (CAS resistant [CAS-R], MIC, >16 mg/liter; CAS intermediate [CAS-I], MIC, 4 mg/liter; and CAS susceptible [CAS-S], MIC, 2 mg/liter). We analyzed tissue fungal burden, histopathology, and weight loss patterns. Increasing CAS resistance was associated with reduced virulence of C. parapsilosis isolates (mortality rates for CAS-S versus CAS-I versus CAS-R, 100% versus 11.1% versus 0%, respectively; P < 0.001). High doses of either echinocandin were active against infection with the CAS-I isolate when assessed by fungal burden reduction and weight gain. In contrast to CAS-S and CAS-I isolates, there was no reduction in fungal burden in mice infected with the CAS-R isolate following treatment with either echinocandin, each given at a high or low dose. Nevertheless, mice infected with the CAS-R isolate had reduced disease severity following echinocandin treatment, suggesting that echinocandins have activity in vivo, even against echinocandin-resistant strains. A complex interplay of residual echinocandin activity, decreased virulence, and/or fitness of isolates with altered cell wall and possible immunomodulatory effects can be encountered in vivo during infection with CAS-resistant C. parapsilosis isolates.

The art of providing resuscitation in Greek mythology.

BACKGROUND: We reviewed Greek mythology to accumulate tales of resuscitation and we explored whether these tales could be viewed as indirect evidence that ancient Greeks considered resuscitation strategies similar to those currently used. METHODS: Three compendia of Greek mythology: The Routledge Handbook of Greek Mythology, The Greek Myths by Robert Graves, and Greek Mythology by Ioannis Kakridis were used to find potentially relevant narratives. RESULTS: Thirteen myths that may suggest resuscitation (including 1 case of autoresuscitation) were identified. Methods to attempt mythological resuscitation included use of hands (which may correlate with basic life support procedures), a kiss on the mouth (similar to mouth-to-mouth resuscitation), application of burning torches (which might recall contemporary use of external defibrillators), and administration of drugs (a possible analogy to advanced life support procedures). A careful assessment of relevant myths demonstrated that interpretations other than medical might be more credible. CONCLUSIONS: Although several narratives of Greek mythology might suggest modern resuscitation techniques, they do not clearly indicate that ancient Greeks presaged scientific methods of resuscitation. Nevertheless, these elegant tales reflect humankind's optimism that a dying human might be restored to life if the appropriate procedures were implemented. Without this optimism, scientific improvement in the field of resuscitation might not have been achieved.

Susceptibility of 2,252 Pseudomonas aeruginosa Clinical Isolates Over 4 Years to 9 Antimicrobials in a Tertiary Greek Hospital.

BACKGROUND: We determined the antimicrobial resistance of and changes over time in Pseudomonas aeruginosa isolates from hospitalized patients over the period of 2010-2013, in relation to the patient setting and clinical specimen origin, in a tertiary Greek hospital. METHODS: All P. aeruginosa isolates collected from patients with nosocomial infections were processed and cultured according to routine methods. The Vitek 2 automated system was used for antimicrobial susceptibility testing against 9 antimicrobials. RESULTS: Overall, 2,252 P. aeruginosa isolates were tested, and 1,124 (49.91%) were found to be fully susceptible. Among 1,128 resistant isolates, 638 (56.56%) were resistant to ≥3 classes of antipseudomonal antibiotics. Intensive care unit isolates were significantly more resistant than surgical and medical ward isolates, while blood and urine isolates demonstrated the highest resistance rates. Resistance was highest in 2012 and lowest in 2013. CONCLUSION: Continuous surveillance of antimicrobial resistance is extremely important for controlling P. aeruginosa infections in the hospital setting.

Risk factors for carbapenem-resistant Klebsiella pneumoniae infection/colonization: a case-case-control study.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is increasingly reported worldwide. The aim of the present study was to identify risk factors associated with the development of CRKP infections. A retrospective, case-case-control study was performed at the University Hospital of Heraklion, Greece. The study population included 83 patients from whom CRKP was isolated, 79 from whom carbapenem-sensitive K. pneumoniae (CSKP) was isolated and 161 (control group) from whom K. pneumoniae was not isolated. The median age of CRKP and CSKP patients was 79 (28-101) and 80 (39-97) years, respectively, while that of the controls was 75 (18-100) years. K. pneumoniae was isolated predominantly from urine in both case groups, followed by blood. Independent risk factors for CRKP infection/colonization were admission to ICU (p = 0.004), prior surgical procedure (p = 0.036) and presence of renal disease (p = 0.037), while for CSKP were neurological disease (p = 0.007), and older age (p = 0.011). No association between CRKP and prior antimicrobial exposure was found. Of the entire cohort 40 patients (12%) died; 22 (27%) in the CRKP, 12 (15%) in the CSKP and 6 (4%) in the control group. Isolation of any K. pneumoniae strain was associated with higher mortality compared to the control group (21% vs. 4%; p < 0.005). Mortality was not statistically different between those infected/colonized/with a CRKP or a CSKP strain (p = 0.084). According to these results prior ICU stay, prior surgical procedure and renal disease were independent risk factors for the development of a CRKP infection/colonization.