Multi-drug resistant Gram-negative bacteria: antibiotic-resistance and new treatment strategies

In this editorial, we treat the multi-drug-resistance of microorganisms such as Klebsiella pneumonia (Kp) and Acinetobacter baumanii and the issues concerning the management of these infections. Diseases caused by carbapenemase-resistant Kp (CR-Kp) represent an emerging threat worldwide due to high mortality rate and limited therapeutic options. Consequently innovative therapies have been suggested for their treatment. Colistin- based combinations are considered the milestone of the therapy for CR-Kp. They include meropenem+colistin, meropenem +colistin+tigecycline, the double carbapenem+colistin, tigecycline+colistin, colistin+gentamicin and even colistin +vancomycin. However, colistin use might be limited by its potential nephrotoxicity and resistance. Other antibiotic combinations concern the tigecycline with gentamicin, fosfomycin with aminoglycoside and ertapenem with meropenem. Thus, the double carbapenem-regimen might be considered as a suitable therapy in those subjects in whom previous antimicrobial combinations failed. New antibiotics such as ceftazidime-avibactam effective on CR-Kp and ceftolozane-tazobactam active against XDR (Extensively Drug Resistant) Pseudomonas aeruginosa are now being used in many countries. The mortality results to be lower in patients treated with antibiotic combinations than in those who underwent monotherapy. Efforts should be made by the clinicians in order to limit the widespread of these resistant microorganisms all over the world. Encouraging new solutions as bacteriophage therapy or biocides currently does not seem the right choice

Antibiotic susceptibility, heteroresistance, and updated treatment strategies in helicobacter pylori infection

In this review, we discuss the problem of antibiotic resistance, heteroresistance, the utility of cultures and antibiotic susceptibility tests in Helicobacter pylori (Hp) eradication, as well as the updated treatment strategies for this infection. The prevalence of antibiotic resistance is increasing all over the world, especially for metronidazole and clarithromycin, because of their heavy use in some geographical areas. Heteroresistance (simultaneous presence of both susceptible and resistant strains in different sites of a single stomach) is another important issue, as an isolate could be mistakenly considered susceptible if a single biopsy is used for antimicrobial tests. We also examined literature data regarding eradication success rates of culture-guided and empiric therapies. The empiric therapy and the one based on susceptibility testing, in Hp eradication, may depend on several factors such as concomitant diseases, the number of previous antibiotic treatments, differences in bacterial virulence in individuals with positive or negative cultures, together with local antibiotic resistance patterns in real-world settings. Updated treatment strategies in Hp infection presented in the guidelines of the Toronto Consensus Group (2016) are reported. These suggest to prolong eradication therapy up to 14 days, replacing the old triple therapy with a quadruple therapy based on proton pump inhibitor (PPI), bismuth, metronidazole, and tetracycline for most of the patients, or as an alternative quadruple therapy without bismuth, based on the use of PPI, amoxicillin, metronidazole, and clarithromycin. The new drug vonoprazan, a first-in-class potassium-competitive acid blocker recently approved in Japan, is also considered to be a promising solution for Hp eradication, even for clarithromycin-resistant strains. Furthermore, there is growing interest in finding new therapeutic strategies, such as the development of vaccines or the use of natural resources, including probiotics, plants, or nutraceuticals.In this review, we discuss the problem of antibiotic resistance, heteroresistance, the utility of cultures and antibiotic susceptibility tests in Helicobacter pylori (Hp) eradication, as well as the updated treatment strategies for this infection. The prevalence of antibiotic resistance is increasing all over the world, especially for metronidazole and clarithromycin, because of their heavy use in some geographical areas. Heteroresistance (simultaneous presence of both susceptible and resistant strains in different sites of a single stomach) is another important issue, as an isolate could be mistakenly considered susceptible if a single biopsy is used for antimicrobial tests. We also examined literature data regarding eradication success rates of culture-guided and empiric therapies. The empiric therapy and the one based on susceptibility testing, in Hp eradication, may depend on several factors such as concomitant diseases, the number of previous antibiotic treatments, differences in bacterial virulence in individuals with positive or negative cultures, together with local antibiotic resistance patterns in real-world settings. Updated treatment strategies in Hp infection presented in the guidelines of the Toronto Consensus Group (2016) are reported. These suggest to prolong eradication therapy up to 14 days, replacing the old triple therapy with a quadruple therapy based on proton pump inhibitor (PPI), bismuth, metronidazole, and tetracycline for most of the patients, or as an alternative quadruple therapy without bismuth, based on the use of PPI, amoxicillin, metronidazole, and clarithromycin. The new drug vonoprazan, a first-in-class potassium-competitive acid blocker recently approved in Japan, is also considered to be a promising solution for Hp eradication, even for clarithromycin-resistant strains. Furthermore, there is growing interest in finding new therapeutic strategies, such as the development of vaccines or the use of natural resources, including probiotics, plants, or nutraceuticals

Immunopathogenesis in Chlamydia trachomatis Infected Women

We examine the Chlamydia trachomatis (Ct) immunopathogenesis on the basis of the complex interaction between host immune response and virulence microorganism factors. Ct infection can be asymptomatic or may produce an inflammation elicited and preserved by reinfections or persistent infections. We discuss the host polymorphisms that, with their anti- or proinflammatory effects, determine the course of the disease. We also took into account the inflammation process following the Chlamydia illness and the role of both CD4 cells producing IFN-γ and CD8 cells with their cytokines production. The crucial role of Ct-hsp60 and the double activity (either damaging or preserving from some kinds of tumors) of anti-Ct-hsp60 antibodies are considered

Pre–Endoscopy Screening of Helicobacter pylori Infection: Implication and Advantages

Different invasive and non-invasive diagnostic tests are available for the diagnosis of Hp in the individual patient. The non-invasive tests obviate the need for endoscopy and can be surely more accepted by the subjects. Moreover the endoscopy has a high cost and provides a marked workload and medical expenses for the hospitals . So the strategy followed by the gastroenterologists but more specifically in general practice is to avoid the endoscopy in patients at low risk of having major pathology. These patients could prevent prompt endoscopy and might safely undergo different managements. It has been proposed [22 23 26] that younger patients with symptoms of dyspepsia with non alarming symptoms could be screened non-invasively for the infection in order to reduce endoscopy procedure. In addition, non-invasive tests are suitable, other than for pre-endoscopy screening of younger dyspeptics, also for use in research and for epidemiological surveys as well as for confirming successful eradication after treatment and for screening asymptomatic population. The pre-endoscopy screening is based on different methodologies (such as serological markers, molecular markers, etc.) that will be discussed in the presen

Prevalence of methicillin-resistant staphylococci isolated from different biological samples at Policlinico Umberto I of Rome: correlation with vancomycin susceptibility

The methicillin-resistance is increasing all over the world in the last decade. It is more frequent among coagulase-negative staphylococci (MRCoNS); infact the 52% of S. epidermidis strains results to be resistant to methicillin.The methicillin-resistant strains also show a reduced sensitivity towards the first-line agents such as glycopeptides and other antibiotics commonly used in therapy such as trimethoprim-sulphamethoxazole, imipenem, gentamycin, fosfomycin and chlarytromicin. Unlike MRSA (Methicillin-resistant S. aureus), MRCoNS resistance to glycopeptides generally concerns teicoplanin. Although vancomycin resistance is rare in Staphylococcus isolates, the detected shift towards higher values of MICs might affect patient's clinical outcome

High potency of melaleuca alternifolia essential oil against multi-drug resistant gram-negative bacteria and methicillin-resistant staphylococcus aureus

Purpose: Herein, an extended investigation of Tea tree oil (TTO) against a number of multi-drug resistant (MDR) microorganisms in liquid and vapor phases is reported. Methods: The activity of TTO was tested against methicillin-sensitive Staphylococcus aureus (MSSA), Escherichia coli, and clinical strains of methicillin-resistant S. aureus (MRSA), extended-spectrum beta lactamases producer carbapenem-sensitive Klebsiella pneumoniae (ESBL-CS-Kp), carbapenem-resistant K. pneumoniae (CR-Kp), Acinetobacter baumannii (CR-Ab), and Pseudomonas aeruginosa (CR-Pa). Minimal inhibitory/bactericidal concentrations (MIC/MBCs) and synergistic activity between TTO and different antimicrobials were determined. In the vapor assay (VP), TTO-impregnated discs were placed on the lid of a petri dish and incubated for 24 h at 37°C. Results: TTO showed a potent bactericidal activity against all the tested microorganisms. TTO in combination with each reference antimicrobial showed a high level of synergism at sub-inhibitory concentrations, particularly with oxacillin (OXA) against MRSA. The VP assay showed high activity of TTO against CR-Ab. Conclusion: Evaluation of in-vitro activity clearly indicated TTO as a potential effective antimicrobial treatment either alone or in association with known drugs against MDR. Therefore, TTO could represent the basis for a possible role in non-conventional regimens against S. aureus and Gram-negative MDR. TTO in VP might represent a promising option for local therapy of pneumonia caused by CR-Ab

Rhodococcus equi Virulence-Associated Antigens and Specific Antibody Response in AIDS Patients Infected with R. equi

ObjectivesTo analyze the expression of the 15- to 17-kDa plasmid-encoded antigens from Rhodococcus equi isolates of 7 AIDS patients and determine the immunologic response to these proteins in the patients' sera.MethodsThe expression of the virulence proteins in R. equi isolates and the specific antibody response were investigated by immunoblotting. Plasmid DNA was analyzed by agarose gel electrophoresis.ResultsThe only patient infected with a strain carrying the virulence 85-kb plasmid and expressing the 15- to 17-kDa antigens developed a fatal pneumonia and did not produce specific antibodies to the virulence proteins. Of the 6 patients infected with R. equi strains lacking both proteins and plasmid, only 1 subject had a pulmonary disease with poor clinical outcome and exhibited a negligible humoral immune response to R. equi antigenic components, whereas the other patients who produced a remarkable antibody response developed either an asymptomatic infection (1 case) or pneumonia (4 cases) which completely cleared up.ConclusionsOur findings suggest that R. equi disease can be induced without the expression of the 15- to 17-kDa virulence-associated plasmid-encoded antigens in HIV-infected patients with very low CD4+ cell counts. Nevertheless, both the synthesis of the virulence proteins and a defective humoral immune response to R. equi may contribute to the severity of rhodococcal disease

Impact of Helicobacter pylori resistance in unsuccessfully pluritreated patients in a Department of Infectious Diseases in Rome

Twenty-five pluritreated patients were examined. Fifty-six percent yielded Helicobacter pylori (H. Pilory); of these, 9 patients showed a concomitant colonization of the three gastric regions. The highest resistance rate was found for metronidazole (71.8%) followed by chlaritromycin (53.1%). Amoxycillin showed the best susceptibility (only 6% of resistance), tetracycline showed 12% of resistant strains and levofloxacin appeared to be a promising antibacterial agent (18% of resistance). The E-test method was shown to be more suitable than disk diffusion technique for resistance testing. Combined resistance to both chlaritromycin and metronidazole appeared in 50% of the strains. The isolates showing this dual resistance are known to be difficult to eradicate. Resistotypes were shown to be genotypically different even if the strains with the resistance to both chlaritromycin and metronidazole are more likely to belong to genotype cagA+ and vacA s1m1. Heteroresistance (different susceptibility of the isolated strains in a single stomach) resulted in 36% of patients with pangastritis. Indeed, the concomitant presence of H. pylori strains in the same subject, either susceptible or resistant or vice versa, may interfere with the eradication outcomes. In our study, antibiotic resistant H. pylori typically develops from pre-existing susceptible strains rather than from co-infection with a different and unrelated strain. In fact, each pair of isolates detected in our 4 patients with heteroresistance belonged to the same genotype (cagA+ s1m2 in patient 1 and cagA+ s1m1 in patients 2, 3 and 4). In conclusion, H. pylori antibiotic resistance does present several issues in pluritreated patients owing to the rapid emergence of multi-resistant strains