In vitro activities of omadacycline, eravacycline, cefiderocol, apramycin, and comparator antibiotics against Acinetobacter baumannii causing bloodstream infections in Greece, 2020-2021: a multicenter study.

Resistance of Acinetobacter baumannii to multiple clinically important antimicrobials has increased to very high rates in Greece, rendering most of them obsolete. The aim of this study was to determine the molecular epidemiology and susceptibilities of A. baumannii isolates collected from different hospitals across Greece. Single-patient A. baumannii strains isolated from blood cultures (n = 271), from 19 hospitals, in a 6-month period (November 2020-April 2021) were subjected to minimum inhibitory concentration determination and molecular testing for carbapenemase, 16S rRNA methyltransferase and mcr gene detection and epidemiological evaluation. 98.9% of all isolates produced carbapenemase OXA-23. The vast majority (91.8%) of OXA-23 producers harbored the armA and were assigned mainly (94.3%) to sequence group G1, corresponding to IC II. Apramycin (EBL-1003) was the most active agent inhibiting 100% of the isolates at ≤16 mg/L, followed by cefiderocol which was active against at least 86% of them. Minocycline, colistin and ampicillin-sulbactam exhibited only sparse activity (S <19%), while eravacycline was 8- and 2-fold more active than minocycline and tigecycline respectively, by comparison of their MIC50/90 values. OXA-23-ArmA producing A. baumannii of international clone II appears to be the prevailing epidemiological type of this organism in Greece. Cefiderocol could provide a useful alternative for difficult to treat Gram-negative infections, while apramycin (EBL-1003), the structurally unique aminoglycoside currently in clinical development, may represent a highly promising agent against multi-drug resistant A. baumanni infections, due to its high susceptibility rates and low toxicity.

Inactivation of mgrB gene regulator and resistance to colistin is becoming endemic in carbapenem-resistant Klebsiella pneumoniae in Greece: A nationwide study from 2014 to 2017.

INTRODUCTION: In Greece, the spread of carbapenem-resistant Enterobacteriaceae in humans has led to the reintroduction of colistin as a therapeutic agent. Unfortunately, colistin resistance with different mechanisms has emerged. The present work aims to determine the prevalence of carbapenem and colistin resistance and the corresponding mechanisms in Klebsiella pneumoniae clinical isolates from Greece. METHODS: From 2014 to 2017, 288 carbapenem-resistant K. pneumoniae clinical strains were gathered from a collection of 973 isolates from eight different hospitals in Greece. Antibiotic susceptibility testing was performed using three different methods. Screening of carbapenem and colistin resistance genes was conducted using polymerase chain reaction (PCR) amplification and sequencing. RESULTS: Among the 288 (29.6 %) carbapenem-resistant isolates, 213 (73.9%) were colistin-resistant (minimum inhibitory concentration [MIC] >2 mg/L). The KPC type was the most common carbapenemase gene (116; 40.3%), followed by VIM (41; 14.2%), NDM (33; 11.5%) and OXA-48 (22; 7.6%). Moreover, 44 (15.3%) strains co-produced two types of carbapenemases. No mcr genes were detected for colistin resistance but mutations in chromosomal genes were found. These included inactivation of the mgrB gene for 148 (69.5%) strains, including insertion sequences for 94 (44.1%), nonsense mutations for 4 (1.9%) and missense mutations for 24 (11.3%). Moreover, PCR amplification of mgrB gene was negative for 26 (12.2%) strains. Finally, 65 (30.5%) colistin-resistant strains exhibited a wild-type mgrB, the mechanisms of which remain to be elucidated. CONCLUSION: This study shows that K. pneumoniae clinical strains in Greece are resistant to both carbapenems and colistin and this is endemic and is likely chromosomally encoded.

Simultaneous Diagnosis of Emphysematous Osteomyelitis and Emphysematous Pyelonephritis in a Diabetic Patient.

BACKGROUND Emphysematous osteomyelitis of the spine is characterized by intravertebral or intraosseous air. Emphysematous pyelonephritis (EP) is the infection of the renal parenchyma and perirenal tissues caused by gas forming microorganisms and thus is characterized by gas formation. Prompt diagnosis and initiation of necessary treatment is crucial, as both entities are associated with high mortality rates. CASE REPORT A 57-year-old female with uncontrolled hyperglycemia presented to the emergency department with history of sudden onset of weakness, nausea, vomiting and diarrhea for 3 days and with a fall on the same level the previous day. Laboratory examinations revealed leukocytosis, lymphopenia, thrombocytopenia, deteriorated renal function, and hyperglycemic hyperosmolar non-ketotic state. She was placed on aggressive intravenous hydration and insulin infusion pump. Due to the deterioration of her medical condition, she underwent abdominal and pelvic CT scanning that revealed emphysematous osteomyelitis of the spine and emphysematous pyelonephritis. Despite vigorous fluid resuscitation and systemic broad-spectrum antibiotic therapy, the patient's condition deteriorated further and eventually led to death within 48 h. CONCLUSIONS This case of fatal emphysematous osteomyelitis of the spine and EP serves as a significant reminder of those rare life-threatening entities, which affect patients with comorbidities, such as diabetes mellitus and other etiologies causing immunosuppression. The aim of the present case report is to highlight the importance and contribution of computed tomography in diagnosing these conditions and to emphasize the rare coexistence of these 2 emphysematous entities.

Nationwide surveillance of resistance rates of Staphylococcus aureus clinical isolates from Greek hospitals, 2012-2013.

Purpose To evaluate the in vitro efficacy of several anti-staphylococcal agents against a nationwide collection of contemporary Staphylococcus aureus clinical isolates from several healthcare centres in Greece. Methods Thirty hospitals throughout Greece (18 in Attica) provided all clinical isolates of S.aureus from April 2012 to May 2013 to a central lab to be re-submitted to susceptibility testing. The MICs were evaluated by Vitek® 2 with the exception of ceftaroline (OXOID M.I.C. Evaluator™). Vancomycin and daptomycin MICs were also evaluated by Etest®. Heterogeneously vancomycin-intermediate strains (hVISA) were detected by the Etest® GRD. VISA phenotype was confirmed by PAP-AUC. Results A total of 1005 isolates (39% MRSA) were studied. Susceptibility rates were: erythromycin 66.5%, clindamycin 79.2%, SXT 98.9%, rifampicin 97.3%, fusidic acid 67%, moxifloxacin 78.8%, vancomycin 99.9%, ceftaroline 92.9% and linezolid, tigecycline and daptomycin 100%. For mupirocin, high level resistance could be excluded for 98.9% of isolates. Vancomycin Etest® MIC50/90 were 1.5/1.5 mg/L, 58.5% of isolates exhibited a MIC > 1 and 8.7% a MIC of 2 mg/L, while Vitek® MIC50/90 were 1/1 and 3.1% showed MIC > 1 mg/L. One VISA strain was detected. Among the selected 175 isolates that were screened for hVISA phenotype, six (3.4%) were positive. In 315 bloodstream isolates, 64.1% had a vancomycin Etest® MIC > 1 mg/L. Conclusions This multi-centre surveillance study revealed that a significant percentage of contemporary S.aureus isolates from Greek patients have a vancomycin MIC (> 1 mg/L) that may compromise the clinical efficacy of the drug for the treatment of serious infections. The in vitro activity of SXT, rifampicin, mupirocin, linezolid, tigecycline, daptomycin and ceftaroline remains excellent.

Risk factors associated with the isolation of colistin-resistant gram-negative bacteria: a matched case-control study.

OBJECTIVE: The emergence of multidrug-resistant gram-negative bacteria has led to the re-use of colistin, but resistance to this agent has already been reported. We aimed to investigate the potential risk factors for the isolation of colistin-resistant Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa from hospitalized patients. DESIGN: Matched case-control study. SETTING: Tertiary care hospital in Athens, Greece. PATIENTS: Case patients were those who had provided a clinical specimen from which a colistin-resistant K. pneumoniae, A. baumannii, or P. aeruginosa was isolated. Controls were selected from a pool of patients who had susceptible to colistin isolates and were matched (1:1) to cases for species of microorganism and site of isolation. Susceptibility to colistin was determined with the Etest. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data regarding patient demographics, comorbidities, admission to the intensive care unit, prior antibiotic use, and invasive procedures performed were analyzed as risk factors in a matched bivariable model. Variables significantly associated with colistin-resistant isolates (p < .05) were entered in a backward multivariable logistic regression model. Forty-one colistin-resistant unique patient isolates were identified from January 1, 2006, until March 31, 2007. These isolates represented infection in 35 of 41 patients. Risk factors significantly associated with the isolation of colistin-resistant isolates were age, duration of intensive care unit stay, [corrected] surgical procedures, use of colistin, use of monobactams, duration of use of colistin and duration of use of antifungal agents [corrected] In the multivariable model, use of colistin was identified as the only independent risk factor (adjusted odds ratio = 7.78, p = .002). CONCLUSIONS: Colistin-resistant K. pneumoniae, A. baumannii, and P. aeruginosa pathogens may be encountered in clinical practice, in association with inappropriate colistin use. To prevent this phenomenon, colistin should be used judiciously, given that treatment options for colistin-resistant gram-negative bacteria are limited.

Risk factors of carbapenem-resistant Klebsiella pneumoniae infections: a matched case control study.

BACKGROUND: Carbapenems are frequently used to treat infections due to extended-spectrum beta-lactamase-producing Klebsiella pneumoniae. Thus, the emergence of infections due to carbapenem-resistant K. pneumoniae (CRKp) is a major public health concern. OBJECTIVES: To identify risk factors associated with the development of CRKp infections. METHODS: We conducted a matched case-control study in two hospitals (Henry Dunant Hospital, Athens, Greece and University Hospital of Heraklion, Crete, Greece). The controls were selected among patients with carbapenem-susceptible K. pneumoniae (CSKp) and were matched with CRKp cases for site of infection. RESULTS: One hundred and six patients were included in our study (53 cases and 53 controls). Mortality was 30.1% and 33.9% for patients with CRKp and CSKp infections, respectively (P = 0.83). Bivariable analysis showed that exposure to anti-pseudomonas penicillins (P = 0.004), carbapenems (P = 0.01), quinolones (P < 0.001) and glycopeptides (P < 0.001), as well as admission to the intensive care unit (P = 0.002), tracheostomy (P = 0.02), chronic obstructive pulmonary disease (P = 0.04), surgery with use of foreign body (P = 0.04) and mechanical ventilation (P = 0.02) were associated with CRKp infection. The multivariable analysis showed that exposure to fluoroquinolones [odds ratio (OR) 4.54, 95% confidence intervals (CIs) 1.78-11.54, P = 0.001] and exposure to antipseudomonal penicillins (OR 2.57, 95% CI 1.00-6.71, P = 0.04) were independent risk factors for CRKp infections. CONCLUSIONS: Our data suggest that prior exposure to fluoroquinolones and antipseudomonal penicillins are independent risk factors for the development of CRKp infections.