Multiresistant Gram-negative Infections Research Articles

A strategy of antimicrobial therapy of pelvic inflammatory diseases at antibiotic resistance of microbial pathogens

Relevance. Antibiotic resistance of microbial pathogens is an interdisciplinary and interstate problem of major medical and socio-economic importance. If multiresistant microbial flora is detected in patients with acute or chronic forms of pelvic inflammatory diseases alternative antimicrobial combined therapy an advisability should be considered. Current trends of an increase in multiresistant gram-negative infections along with limited range of alternative treatment options dictate a need for further research. Study of alternative antibiotics effectiveness in pelvic inflammatory diseases treatment is necessary for a further development of optimal treatment regimens. Aim. To search for adequate combinations of antimicrobial therapy aimed at antibiotic-resistant pathogens. Materials and methods. To write this review a search for domestic and foreign publications in Russian and international search systems (PubMed, eLibrary, etc.) for the last 2-12 years was conducted. The review includes articles from peer-reviewed literature. Results. Fosfomycin possesses a broad spectrum of antibacterial effects including gram-positive and gram-negative aerobic bacteria. The drug is highly effective against Pseudomonas aeruginosa and Escherichia coli, anaerobic bacteria (Proteus mirabilis and Klebsiella pneumoniae) as well as against gram- positive bacteria (Staphylococcus spp., including S. aureus, S. epidermidis; Streptococcus spp., including Enterococcus faecalis). Conclusions. When multiresistant microbial flora is detected in patients with acute or chronic forms of pelvic inflammatory diseases an advisability of fosfomycin administration should be considered.

Virulence and Stress Responses of Shigella flexneri Regulated by PhoP/PhoQ.

The two-component signal transduction system PhoP/PhoQ is an important regulator for stress responses and virulence in most Gram-negative bacteria, but characterization of PhoP/PhoQ in Shigella has not been thoroughly investigated. In the present study, we found that deletion of phoPQ (ΔphoPQ) from Shigella flexneri 2a 301 (Sf301) resulted in a significant decline (reduced by more than 15-fold) in invasion of HeLa cells and Caco-2 cells, and less inflammation (− or +) compared to Sf301 (+++) in the guinea pig Sereny test. In low Mg2+ (10 μM) medium or pH 5 medium, the ΔphoPQ strain exhibited a growth deficiency compared to Sf301. The ΔphoPQ strain was more sensitive than Sf301 to polymyxin B, an important antimicrobial agent for treating multi-resistant Gram-negative infections. By comparing the transcriptional profiles of ΔphoPQ and Sf301 using DNA microarrays, 117 differentially expressed genes (DEGs) were identified, which were involved in Mg2+ transport, lipopolysaccharide modification, acid resistance, bacterial virulence, respiratory, and energy metabolism. Based on the reported PhoP box motif [(T/G) GTTTA-5nt-(T/G) GTTTA], we screened 38 suspected PhoP target operons in S. flexneri, and 11 of them (phoPQ, mgtA, slyB, yoaE, yrbL, icsA, yhiWX, rstA, hdeAB, pagP, and shf–rfbU-virK-msbB2) were demonstrated to be PhoP-regulated genes based on electrophoretic mobility shift assays and β-galactosidase assays. One of these PhoP-regulated genes, icsA, is a well-known virulence factor in S. flexneri. In conclusion, our data suggest that the PhoP/PhoQ system modulates S. flexneri virulence (in an icsA-dependent manner) and stress responses of Mg2+, pH and antibacterial peptides.

Colistin nephrotoxicity in the ICU: Is it different in the geriatric patients?

Most significant side effect of colistin therapy which is used for the treatment of multi-drug resistant Gram-negative infections is nephrotoxicity. Our aim was to investigate the differences of colistin nephrotoxicity between the geriatric age group (≥65years) and the younger age group (<65years) in critically ill medical intensive care unit (ICU) patients. The medical records of the 76 patients who were taken colistin therapy due to multi-resistant Gram-negative infections between January 2010 and June 2014 in the our medical ICU were retrospectively investigated. Demographic characteristics, reasons for colistin use, daily colistin dose, duration of colistin use were recorded. Colistin-dependent renal dysfunction was evaluated according to the risk, injury, failure, loss and end-stage renal failure (RIFLE) criterias. The median age of the patients was 65 (65.8% male). Nephrotoxicity was developed in 36 (47.4%) patients. Thirty-nine (51.3%) patients were in geriatric age group, 37 (48.7%) were in younger age group. In geriatric age group, the rates of male gender (53.8 vs 78.4%, p = 0.031), pulmonary (48.7 vs 16.2%, p = 0.003) and cardiac diseases (71.8 vs 29.7%, p < 0.001), post-nephrotoxicity BUN levels (p = 0.023) and urine output during nephrotoxicity (p = 0.016) were higher than younger age group. Nephrotoxicity was developed in 22 (56.4%) patients of geriatric age group, and in 14 (37.8%) patients in younger age group (p = 0.115). The presence of cardiac disease, renal pathology and high creatinin value on admission, daily amount of colistin per body mass, total amount of colistin, use of colistin for pulmonary infection, use of amphotericin and vasopressor on admission were found as risk factors for colistin nephrotoxicity development in all study group; the daily amount of colistin per body mass (risk ratio:0.41; 95% CI 0.19-0.89) and vasopressor use during hospitalization were found independent risk factors (risk ratio:13.54; 95% CI 2.21-83.09). In our study, in geriatric patient group colistin nephrotoxicity was not different from the younger age group. In the ICU, the age for nephrotoxicity does not appear to be a point to be considered for the initiation of colistin.

Colistin-resistant Escherichia coli clinical isolate harbouring the mcr-1 gene in Ecuador.

Colistin resistance mediated by the mcr-1 gene has been reported worldwide, but to date not from the Andean region, South America. We report the first clinical isolate of Escherichia coli harbouring the mcr-1 gene in Ecuador. The strain was isolated from peritoneal fluid from a 14-year-old male with acute appendicitis, and subjected to molecular analysis. The minimum inhibitory concentration of colistin for the strain was 8 mg/ml and it was susceptible to carbapenems but resistant to tigecycline. The strain harboured mcr-1 and bla CTX-M-55 genes and was of sequence type 609. The recognition of an apparently commensal strain of E. coli harbouring mcr-1 serves as an alert to the presence in the region of this recently described resistance mechanism to one of the last line of drugs available for the treatment of multi-resistant Gram-negative infections.

Multiresistant Gram-negative infections: a global perspective

Multiresistant Gram-negative infections are an increasing problem in hospitals and healthcare facilities worldwide. While much attention has been paid to Gram-positive pathogens such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus lately, the importance of Gram-negative nosocomial infections has also been recognized globally. Recent reports have described the spread of carbapenemase-producing Klebsiella pneumoniae across North America. In addition, many strains of Pseudomonas and Acinetobacter in Asia are resistant to all known antibiotics. The global epidemiology of multiresistant Gram-negative pathogens seems to vary by continent. There are very few existing agents which can be used for these pathogens and there are limited options on the horizon. This limited therapeutic armamentarium has been an impetus for novel approaches including combination therapies and increased attention to infection control and prevention efforts. Clinicians need to be aware of the rising problem of resistance in nosocomial and community-acquired Gram-negative pathogens. Novel agents are urgently needed to combat these infections and innovative infection control strategies need to be devised to protect our vulnerable patients.

Use of colistin in treating multi-resistant Gram-negative organisms in a specialised burns unit

Patients with burns are at an increased risk of infection which can affect their outcome-duration of hospital stay, intensive care requirements, organ support, inotrope requirements, renal replacement therapy, ventilatory requirements and overall mortality. Our study aimed to evaluate the use of colistin in our burns intensive care unit (ICU) in treating multi-resistant Gram-negative infections. This was a retrospective study carried out in a regional referral centre for burns and plastics, Chelmsford, UK. We looked at data from patients admitted to our intensive care over a two-year period from November 2003 to November 2005. All patients who received colistin were included in the study. Admission data included demographic data and burn data, other relevant medical history, and blood results. We also recorded: length of ICU stay, ultimate outcome, total dose of colistin, repeated doses, and mode of drug delivery, organ support, organisms grown and their resistance. Response to colistin was judged by improvement in clinical status, decrease in white blood cell count (WCC) and inflammatory markers and no growth on cultures. The data were subjected to non-parametric Wilcoxon Signed Rank Test using SPSS version 14. Twenty-nine patients were included in the study all of whom received colistin in one form or the other. The average total dose of colistin was 69 million units (range 1–268). Of these, 17 patients survived (58.6%) and 12 died (41.4%). Twenty patients improved (69%) and 9 did not improve (31%) after administration of colistin. We also compared creatinine levels on admission and post colistin. We used non-parametric Wilcoxon Signed Rank test which showed no difference in the two groups ( p = 0.38). We found colistin to be safe and effective in treating multi-resistant Gram-negative infections in burns patients and we did not see any statistically significant impairment of renal function.

Use of colistin to treat multiresistant Gram-negative infections in a specialised burns unit

Use of colistin to treat multiresistant Gram-negative infections in a specialised burns unit

Polymyxin B nephrotoxicity and efficacy against nosocomial infections caused by multiresistant gram-negative bacteria.

Reported rates of nephrotoxicity associated with the systemic use of polymyxins have varied widely. The emergence of infections due to multiresistant gram-negative bacteria has necessitated the use of systemic polymyxin B once again for the treatment of such infections. We retrospectively investigated the rate of nephrotoxicity in patients receiving polymyxin B parenterally for the treatment of infections caused by multiresistant gram-negative bacteria from October 1999 to September 2000. Demographic and clinical information was obtained for 60 patients. Outcome measures of interest were renal toxicity and clinical and microbiologic efficacy. Renal failure developed in 14% of the patients, all of whom had normal baseline renal function. Development of renal failure was independent of the daily and cumulative doses of polymyxin B and the length of treatment but was significantly associated with older age (76 versus 59 years, P = 0.02). The overall mortality was 20%, but it increased to 57% in those who developed renal failure. The organism was cleared in 88% of the patients from whom repeat specimens were obtained. The use of polymyxin B to treat multiresistant gram-negative infections was highly effective and associated with a lower rate of nephrotoxicity than previously described.

Ceftazidime, as a single antibiotic, in the treatment of multi-resistant Gram-negative infections in intensive care

In this study we have evaluated the efficacy and tolerance of ceftazidime used as the only antibiotic in the treatment of 19 critically ill patients, with serious infections caused by multiply resistant Gram-negative bacilli in an intensive care unit. The bacteria isolated showed a high susceptibility to ceftazidime and a moderate resistance to seven other antibiotics. Clinical improvement occurred in 42.1% of the patients treated. Tolerance, both local and general, to the drug was considered good. Ceftazidime appeared to be capable of replacing beta-lactam and aminoglycoside combinations in the treatment of serious infections caused by Gram-negative species in ICUs, but further experience is necessary.