Mechanisms of Antibiotic Resistance in Important Gram-Positive and Gram-Negative Pathogens and Novel Antibiotic Solutions.

Multidrug-resistant bacteria have on overwhelming impact on human health, as they cause over 670,000 infections and 33,000 deaths annually in the European Union alone. Of these, the vast majority of infections and deaths are caused by only a handful of species-multi-drug resistant Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Enterococcus spp., Acinetobacter spp. and Klebsiella pneumoniae. These pathogens employ a multitude of antibiotic resistance mechanisms, such as the production of antibiotic deactivating enzymes, changes in antibiotic targets, or a reduction of intracellular antibiotic concentration, which render them insusceptible to multiple antibiotics. The purpose of this review is to summarize in a clinical manner the resistance mechanisms of each of these 6 pathogens, as well as the mechanisms of recently developed antibiotics designed to overcome them. Through a basic understanding of the mechanisms of antibiotic resistance, the clinician can better comprehend and predict resistance patterns even to antibiotics not reported on the antibiogram and can subsequently select the most appropriate antibiotic for the pathogen in question.

Characterization of 16S rRNA methylase genes in Enterobacterales and Pseudomonas aeruginosa in Athens Metropolitan area, 2015-2016.

The aim of this study was to characterize the 16S rRNA methylase (RMT) genes in aminoglycoside-resistant Enterobacterales and Pseudomonas aeruginosa isolates in 2015-2016 in hospitals in Athens, Greece. Single-patient, Gram-negative clinical isolates resistant to both amikacin and gentamicin (n = 292) were consecutively collected during a two-year period (2015-2016) in five tertiary care hospitals in Athens. RMT genes were detected by PCR. In all RMT-producing isolates, ESBL and carbapenemase production was confirmed by PCR, and the clonal relatedness and the plasmid contents were also characterized. None of the 138 P. aeruginosa isolates harbored any of the RMT genes surveyed although some were highly resistant to aminoglycosides (MICs > = 512 mg/L). Among 154 Enterobacterales, 31 Providencia stuartii (93.9%), 42 Klebsiella pneumoniae (37.8%), six Proteus mirabilis (75%), and two Escherichia coli (100%) isolates were confirmed as highly resistant to amikacin, gentamicin, and tobramycin with MICs ≥ 512 mg/L, harboring mainly the rmtB (98.8%). All were carbapenemase producers. P. stuartii, P. mirabilis, and E. coli produced VIM-type carbapenemases. K. pneumoniae produced KPC- (n = 34, 81.0%), OXA-48 (n = 4, 9.5%), KPC- and VIM- (n = 3, 7.1%), or only VIM-type (n = 1, 2.4%) enzymes. Two groups of similar IncC plasmids were detected one harboring rmtB1, blaVEB-1, blaOXA-10, and blaTEM-1, and the other additionally blaVIM-1 and blaSHV-5. Among RMT-producing Enterobacterales, rmtB1 predominated and was associated with carbapenemase-encoding gene(s). Similar IncC plasmids carrying a multiresistant region, including ESBL genes, and in the case of VIM-producing isolates, the blaVIM-1, were responsible for this dissemination. The co-dissemination of these genes poses a public health threat.

Response to COVID-19 in Cyprus: Policy changes and epidemic trends.

OBJECTIVES: In late July, Cyprus experienced the second epidemic wave of COVID-19. We present the steps taken by the government and evaluate their effect on epidemic trends. MATERIALS: Cyprus Press and Information Office data were analysed. Using an R-based forecasting program, two models were created to predict cases up to 01/09/2020: Model 1, which utilised data up to 09/06/2020, when airports reopened to foreign travelers with COVID-19 screening; and Model 2, which utilised data until 24/06/2020, when screening for passengers from low-transmission countries was discontinued. RESULTS: PIO data revealed no significant policy changes between 24/06/2020 and 31/07/2020. Prediction models were robust and accurate (Model 1, R2  = 0.999, P < .001; Model 2, R2  = 0.998, P < .001). By August 30th, recorded cases exceeded those predicted by Model 1 by 24.47% and by Model 2 by 20.95%, with P values <.001 for both cases. CONCLUSIONS: The significant difference between recorded cases and those projected by Models 1 and 2 suggests that changes in epidemic trends may have been associated with policy changes after their respective dates. Discontinuation of major restrictions such as airport reopening, can destabilise the control of the epidemic, and may concomitantly necessitate a reevaluation of the current epidemic status. In the face of an evolving situation such as the COVID-19 pandemic, states are forced to balance the imposing of restrictions against their impact on the economy.

Dissemination of International Clone II Acinetobacter baumannii Strains Coproducing OXA-23 Carbapenemase and 16S rRNA Methylase ArmA in Athens, Greece.

The aim of this study was to study the molecular epidemiology of 16S rRNA-methylase (RMT)-producing clinical Acinetobacter baumannii isolates from hospitals in Athens, Greece. Single-patient A. baumannii clinical isolates, coresistant to amikacin and gentamicin (n = 347), from five tertiary care hospitals, were submitted to minimum inhibitory concentration determination and molecular testing for carbapenemase and RMT genes. A. baumannii, resistant to amikacin and gentamicin, was isolated at participating institutions at a mean rate of 67.8%. Among them 93.7% harbored the armA. The vast majority (98.5%) of armA positive isolates were OXA-23 producers, assigned mainly (99.4%) to sequence group G1, corresponding to international clone (IC) II. Four isolates (all from the same hospital) were OXA-24 producers (1.2%), assigned to G6 corresponding to CC78 and only one isolate was OXA-58-producer, assigned to G2 (IC I). Apramycin was the most active agent inhibiting 99.7% of the isolates at ≤64 mg/L, whereas colistin, trimethoprim/sulfamethoxazole, minocycline, and tigecycline exhibited only sparse activity (S, <18%). RMT production is an emerging mechanism of resistance, capable of compromising the clinical efficacy of aminoglycosides. High prevalence of armA was observed among A. baumannii strains isolated in participating hospitals in Athens, which were mainly OXA-23 producers and belonged to IC II. Apramycin is a structurally unique aminoglycoside, currently used as a veterinary agent. Although it has not been evaluated for clinical use, apramycin appears worthy of further investigation for repurposing as a human therapeutic against difficult-to-treat pathogens.

Shiga toxin-induced haemolytic uraemic syndrome and the role of antibiotics: a global overview.

OBJECTIVES: The administration of antibiotics in infections caused by Shiga toxin producing E. coli (STEC) strains, such as O157:H7, was and remains controversial, as it has been associated with the development of haemolytic uraemic syndrome (HUS). We conducted a literature review to better examine this association. METHODS: We searched the PubMed and Google Scholar databases for relevant articles, using the key words: ``haemolytic uraemic syndrome'', ``Shiga toxin'', ``E. coli O157:H7'', ``E. coli O104:H4'', ``STEC colitis'', ``STEC antibiotics'', ``STEC fosfomycin'', ``STEC trimethoprim sulfamethoxazole'', ``STEC fluoroquinolones'', ``STEC ciprofloxacin'', ``STEC rifaximin'', ``STEC gentamycin'', ``STEC colistin'', "Shiga toxin binding agent", "Shiga toxin monoclonal antibody" and ``STEC Japan epidemic''. RESULTS: Numerous studies report that antibiotics increase the risk of HUS development, while others report that antibiotics do not have any effect or can even reduce the rate of HUS development in STEC infections. The infecting STEC strain, the type of antibiotic as well as the timing of its administration appear to significantly affect the development of HUS in a STEC infected patient. CONCLUSIONS: It appears that, while some antibiotics such as b-lactams and TMP/SMX may be detrimental, others appear to be safe and can prevent the development of HUS. Of note, fosfomycin appears to be the antibiotic with the most positive results from clinical studies, and may be able to avert HUS development, especially if administered within the first two or three days from diarrhoea onset. Fluoroquinolones have also shown positive outcomes in clinical studies, despite demonstrating unfavourable results in in vitro studies. Other agents, such as colistin, gentamycin and rifamycins, have shown promising results in in vitro studies and require further evaluation.

Prevalence of Mycoplasma genitalium and other sexually-transmitted pathogens among high-risk individuals in Greece.

BACKGROUND: The aim of the present study was to determine the prevalence of Mycoplasma genitalium (MG) infection among individuals at high risk for sexually-transmitted diseases (STDs) at a major urban STD clinic in Athens, in view of the lack of data pertaining to this infection in Greece. METHODS: Urethral and cervical samples from 176 individuals consecutively attending the clinic and agreeing to participate were prospectively collected and tested for MG infection using conventional PCR and TaqMan Real-Time PCR. All individuals were also examined for alternative STD pathogens. RESULTS: A total of 161 individuals (91.5%) reported symptoms, while 15 individuals (8.5%) were asymptomatic. MG was detected in 5.7% (10/176) of the total population and in 5.6% (9/161) of those with symptoms, corresponding to 5.7% (5/87) of symptomatic men and 5.4% (4/74) of symptomatic women. Among symptomatic males, 3.4% (3/87) displayed MG mono-infection. The median age of MG infected individuals was 25 years (IQR 21.5-29.5 years). Individuals infected with MG were more likely to be coinfected with Ureaplasma spp. [OR=5.12, 95%CI, 1.27-20.57] (p=0.017). MG infection was also more common among individuals who had received antibiotics in the previous 15 days [OR=6.04, 95%CI, 1.37-26.64] (p=0.035). CONCLUSION: MG was found to represent an important microbial pathogen among patients presenting with symptoms of urethritis or cervicitis in Greece. Consideration of MG as cause of STD seems crucial in diagnostic algorithms and treatment strategies.

Differential diagnosis and treatment of acute cauda equina syndrome in the human immunodeficiency virus positive patient: a case report and review of the literature.

BACKGROUND: Acute cauda equina syndrome is an uncommon but significant neurologic presentation due to a variety of underlying diseases. Anatomical compression of nerve roots, usually by a lumbar disk hernia is a common cause in the general population, while inflammatory, neoplastic, and ischemic causes have also been recognized. Among human immunodeficiency virus (HIV) infected patients with acquired immunodeficiency syndrome, infectious causes are encountered more frequently, the most prevalent of which are: cytomegalovirus, herpes simplex virus 1/2, varicella zoster virus, and Mycobacterium tuberculosis infections. Studies of cauda equina syndrome in well-controlled HIV infection are lacking. We describe such a case of cauda equina syndrome in a well-controlled HIV-infected patient, along with a brief review of the literature regarding the syndrome's diagnosis and treatment in individuals with HIV infection. CASE PRESENTATION: A 36-year-old Greek male, HIV-positive patient presented with perineal and left hemiscrotal numbness, lumbar pain, left-sided sciatica, and urinary incontinence. Magnetic resonance imaging of the patient's lumbar spine revealed intrathecal migration of a fragment from an intervertebral lumbar disk exerting pressure on the cauda equina. A cerebrospinal fluid examination, brain computed tomography scan, spine magnetic resonance imaging, and serological test results were negative for central nervous system infections. Our patient underwent emergency neurosurgical spinal decompression, which resolved most symptoms, except for mild urinary incontinence. CONCLUSIONS: Noninfectious etiologies may also cause cauda equina syndrome in HIV-infected individuals, especially in well-controlled disease under antiretroviral therapy. Prompt recognition and treatment of the underlying cause is important to minimize residual symptoms. Targeted antimicrobial chemotherapy is used to treat infectious causes, while prompt surgical decompression is favored for anatomical causes of cauda equina syndrome in the HIV-infected patient.

Epidemiology of Hantavirus infections in humans: a comprehensive, global overview.

Hantaviruses comprise an emerging global threat for public health, affecting about 30,000 humans annually. Infection may lead to Hantavirus pulmonary syndrome (HPS) in the Americas and hemorrhagic fever with renal syndrome (HFRS) in the Europe and Asia. Humans are spillover hosts, acquiring infection primarily through the inhalation of aerosolized excreta from infected rodents and insectivores. Risk factors for infection include involvement in outdoor activities, such as rural- and forest-related activities, peridomestic rodent presence, exposure to potentially infected dust and outdoor military training; prolonged, intimate contact with infected individuals promotes transmission of Andes virus, the only Hantavirus known to be transmitted from human-to-human. The total number of Hantavirus case reports is generally on the rise, as is the number of affected countries. Knowledge of the geographical distribution, regional incidence and associated risk factors of the disease are crucial for clinicians to suspect and diagnose infected individuals early on. Climatic, ecological and environmental changes are related to fluctuations in rodent populations, and subsequently to human epidemics. Thus, prevention may be enhanced by host-reservoir control and human exposure prophylaxis interventions, which likely have led to a dramatic reduction of human cases in China over the past decades; vaccination may also play a role in the future.

Red man syndrome adverse reaction following intravenous infusion of cefepime.

We report the first case of cefepime-induced "red-man syndrome," which appeared 30 min following drug infusion and was confirmed with a rechallenge test. This syndrome is classically associated with vancomycin infusion and is the result of non-IgE mediated mast cell degranulation. While this adverse effect can be easily managed with drug withdrawal and antihistamine administration, it is unknown whether it can be prevented with slower cefepime infusion and preinfusion antihistamines, as is the case with vancomycin.

Hantavirus infections for the clinician: from case presentation to diagnosis and treatment.

Hantaviruses cause Hantavirus Pulmonary Syndrome (HPS; also called Hantavirus Cardiopulmonary Syndrome) in the Americas and Hemorrhagic Fever with Renal Syndrome (HFRS) in Asia and Europe. In Scandinavia and northern Europe, a milder form of HFRS is prevalent, termed nephropathica epidemica (NE). HPS presents with acute respiratory failure, mild-moderate renal failure, thrombocytopenia, and reactive lymphocytosis. HFRS has pronounced renal dysfunction and less prominent respiratory involvement, with thrombocytopenia and hemorrhagic findings. Both syndromes have long-term sequelae. Common symptomatology is due to underlying pathophysiology, mainly increased vascular permeability and immune activation. Laboratory and imaging markers predicting disease severity are under research, allowing for more efficient patient management. Diagnosis is presumptive, based on typical clinical findings and patient history of likely rodent exposure. Confirmation of diagnosis is by serological testing and/or RT-PCR. Treatment is mainly comprised of cardiovascular, respiratory, and renal function support, with fluid and electrolyte homeostasis being crucial components of care. In HPS, the use of extracorporeal membrane oxygenation in decompensated patients has also shown to be beneficial.