Combination Of Aminoglycoside Research Articles

Combination therapy with IV fosfomycin for adult patients with serious Gram-negative infections: a review of the literature.

Treatment of patients with serious infections due to resistant Gram-negative bacteria remains highly problematic and has prompted clinicians to use existing antimicrobial agents in innovative ways. One approach gaining increased therapeutic use is combination therapy with IV fosfomycin. This article reviews the preclinical pharmacokinetic/pharmacodynamic (PK/PD) infection model and clinical data surrounding the use of combination therapy with IV fosfomycin for the treatment of serious infections caused by resistant Gram-negative bacteria. Data from dynamic in vitro and animal infection model studies of highly resistant Enterobacterales and non-lactose fermenters are positive and suggest IV fosfomycin in combination with a β-lactam, polymyxin or aminoglycoside produces a synergistic effect that rivals or surpasses that of other aminoglycoside- or polymyxin-containing regimens. Clinical studies performed to date primarily have involved patients with pneumonia and/or bacteraemia due to Klebsiella pneumoniae, Pseudomonas aeruginosa or Acinetobacter baumannii. Overall, the observed success rates with fosfomycin combination regimens were consistent with those reported for other combination regimens commonly used to treat these patients. In studies in which direct treatment comparisons can be derived, the results suggest that patients who received fosfomycin combination therapy had similar or improved outcomes compared with other therapies and combinations, especially when it was used in combination with a β-lactam that (1) targets PBP-3 and (2) has exceptional stability in the presence of β-lactamases. Collectively, the data indicate that combination therapy with IV fosfomycin should be considered as a potential alternative to aminoglycoside or polymyxin combinations for patients with antibiotic-resistant Gram-negative infections when benefits outweigh risks.

Potentiation by Protein Synthesis Inducers of Translational Readthrough of Pathogenic Premature Termination Codons in PTEN Isoforms.

The PTEN tumor suppressor is frequently targeted in tumors and patients with PTEN hamartoma tumor syndrome (PHTS) through nonsense mutations generating premature termination codons (PTC) that may cause the translation of truncated non-functional PTEN proteins. We have previously described a global analysis of the readthrough reconstitution of the protein translation and function of the human canonical PTEN isoform by aminoglycosides. Here, we report the efficient functional readthrough reconstitution of the PTEN translational isoform PTEN-L, which displays a minimal number of PTC in its specific N-terminal extension in association with disease. We illustrate the importance of the specific PTC and its nucleotide proximal sequence for optimal readthrough and show that the more frequent human PTEN PTC variants and their mouse PTEN PTC equivalents display similar patterns of readthrough efficiency. The heterogeneous readthrough response of the different PTEN PTC variants was independent of the length of the PTEN protein being reconstituted, and we found a correlation between the amount of PTEN protein being synthesized and the PTEN readthrough efficiency. Furthermore, combination of aminoglycosides and protein synthesis inducers increased the readthrough response of specific PTEN PTC. Our results provide insights with which to improve the functional reconstitution of human-disease-related PTC pathogenic variants from PTEN isoforms by increasing protein synthesis coupled to translational readthrough.

Efficacy and safety of therapeutic strategies for human brucellosis: A systematic review and network meta-analysis.

Human brucellosis is a neglected, re-emerging, and endemic zoonosis in many countries. The debilitating and disabling potential of the disease is a warning about its morbidity, generating socioeconomic impact. This review aims to update the current evidence on the efficacy and safety of therapeutic options for human brucellosis using the network meta-analysis (NMA). A systematic search was conducted in four different databases by independent reviewers to assess overall therapy failure, adverse events, and time to defervescence associated with different therapies. Randomized clinical trials (RCTs) evaluating any therapeutic drug intervention were selected, excluding non-original studies or studies related to localized forms of the disease or with less than 10 participants. Data were analyzed by frequentist statistics through NMA by random effects model. The risk of bias and certainty of evidence was assessed, this review was registered at PROSPERO. Thirty-one (31) RCTs involving 4167 patients were included. Three networks of evidence were identified to evaluate the outcomes of interest. Triple therapy with doxycycline + streptomycin + hydroxychloroquine for 42 days (RR: 0.08; CI 95% 0.01-0.76) had a lower failure risk than the doxycycline + streptomycin regimen. Doxycycline + rifampicin had a higher risk of failure than doxycycline + streptomycin (RR: 1.96; CI 95% 1.27-3.01). No significant difference was observed between the regimens when analyzing the incidence of adverse events and time to defervescence. In general, most studies had a high risk of bias, and the results had a very low certainty of evidence. This review confirmed the superiority of drugs already indicated for treating human brucellosis, such as the combination of doxycycline and aminoglycosides. The association of hydroxychloroquine to the dual regimen was identified as a potential strategy to prevent overall therapy failure, which is subject to confirmation in future studies.

ORBITAL COMPLICATIONS OF SINUSITIS–RETROSPECTIVE ANALYSIS

Objective: The objective of this study is to consider and analyze patients who were treated for these complications in the last 2 years in our hospital, comparing with another 2 tertiary care hospitals. Methods: It is a retrospective study. Out of the total number of ear, nose, and throat ENT cases attending our outpatient department, cases treated in the hospital with rhinosinusitis where surgical intervention is necessary, or those with a suspicion of complications. Between 2017 and 2019, there were 25 cases from three tertiary care hospitals, the clinical charts of which were reviewed. Consent has been taken from all the participants. The cases that are excluded from this study are those involving soft tissues, bone, and with intracranial complications. The diagnoses were determined based on history, anterior rhinoscopy, radiological imaging of the paranasal sinuses (X-ray), or computed tomography scan taken where there was a suspicion of a complication. In all cases, intensive treatment was initiated with a combination of cephalosporins and aminoglycosides and nasal irrigation with saline sprays. Results: In our study, in GITAM Institute of Medical Sciences and Research we encountered 6 cases the average time that patients remained in hospital was 4–5 days; for those with orbital complications this was 7 days. Similarly in other two tertiary care hospitals Andhra Medical College Visakhapatnam encountered around 15 cases and Konaseema Institute of Medical Science, Amalapuram, encountered 4 cases total constituting of 25 cases. Conclusion: The appearance of edema in the corner of the eye should be evaluated immediately, and the means to exclude acute sinusitis should be taken under serious consideration. Early diagnosis and aggressive treatment are important steps to be taken to avoid orbital complications like loss of vision.

Variation in antibiotic consumption in very preterm infants-a 10 year population-based study.

Wide variations in antibiotic use in very preterm infants have been reported across centres despite similar rates of infection. We describe 10 year trends in use of antibiotics and regional variations among very preterm infants in Norway. All live-born very preterm infants (<32 weeks gestation) admitted to any neonatal unit in Norway during 2009-18 were included. Main outcomes were antibiotic consumption expressed as days of antibiotic therapy (DOT) per 1000 patient days (PD), regional variations in use across four health regions, rates of sepsis and sepsis-attributable mortality and trends of antibiotic use during the study period. We included 5296 infants: 3646 (69%) were born at 28-31 weeks and 1650 (31%) were born before 28 weeks gestation with similar background characteristics across the four health regions. Overall, 80% of the very preterm infants received antibiotic therapy. The most commonly prescribed antibiotics were the combination of narrow-spectrum β-lactams and aminoglycosides, but between 2009 and 2018 we observed a marked reduction in their use from 100 to 40 DOT per 1000 PD (P < 0.001). In contrast, consumption of broad-spectrum β-lactams remained unchanged (P = 0.308). There were large variations in consumption of vancomycin, broad-spectrum β-lactams and first-generation cephalosporins, but no differences in sepsis-attributable mortality across regions. The overall antibiotic consumption was reduced during the study period. Marked regional variations remained in consumption of broad-spectrum β-lactams and vancomycin, without association to sepsis-attributable mortality. Our results highlight the need for antibiotic stewardship strategies to reduce consumption of antibiotics that may enhance antibiotic resistance development.

Comparative Investigation into the Roles of Imipenem:Cyclodextrin Complexation and Antibiotic Combination in Combatting Antimicrobial Resistance in Gram-Negative Bacteria.

Extensively drug-resistant (XDR), multidrug-resistant (MDR) and pandrug-resistant (PDR) Gram-negative microorganisms (GNBs) are considered a significant global threat. β-lactam and aminoglycoside combinations and imipenem:cyclodextrin inclusion complexes were studied for the treatment of lethal GNBs. This is because of the broad empiric coverage of the two drugs and their possession of different spectra of activity. Two cyclodextrins (β- and hydroxy propyl β-cyclodextrins) were utilized for inclusion complex formation with imipenem using the physical and kneading methods. In silico investigation using the molecular docking and Fourier-infrared spectroscopy (FTIR) were employed to estimate binding constant and confirm complex formation, respectively. The in vitro effects of amikacin and imipenem combination in comparison to the effect of imipenem-β- and hydroxy propyl β-cyclodextrin (CD) complexes against Klebsiella spp. and Acinetobacter baumannii were studied. The isolated microorganisms' antimicrobial responsiveness to various antibiotics (19 antibiotics) was evaluated. It was found that piperacillin/tazobactam and gentamycin (resistance rates were 33.3% and 34%, respectively) were the most effective antimicrobials. The in vitro studies have been performed by the checkerboard technique and time-killing assay. The studied combination of amikacin and imipenem showed a substantial drop in bacterial count (p < 0.05). The in vitro studies demonstrated a synergism for the investigated combination. Conventional PCR was used in molecular studies to identify the resistance genes bla IMP and aac (6')-Ib. The blaIMP and aac (6')-Ib were recorded in 38.2% and 3.6% of the studied isolates, respectively. The in vitro studies showed synergistic effects among the tested antibiotics with FICIs of ≤0.5. Finally, the study compared the reduction in bacterial count between the tested antibiotic combinations and imipenem:CD physical and kneaded mixtures. Imipenem:CD inclusion complexes demonstrated a significant bacterial count reduction over the antibiotic combination. These results highlight the emerging role of CDs as safe biofunctional excipients in the combat against superbug bacterial resistance.

A novel ruthenium-silver based antimicrobial potentiates aminoglycoside activity against Pseudomonas aeruginosa.

The rapid dissemination of antibiotic resistance combined with the decline in the discovery of novel antibiotics represents a major challenge for infectious disease control that can only be mitigated by investments in novel treatment strategies. Alternative antimicrobials, including silver, have regained interest due to their diverse mechanisms of inhibiting microbial growth. One such example is AGXX, a broad-spectrum antimicrobial that produces highly cytotoxic reactive oxygen species (ROS) to inflict extensive macromolecular damage. Due to the connections identified between ROS production and antibiotic lethality, we hypothesized that AGXX could potentially increase the activity of conventional antibiotics. Using the gram-negative pathogen Pseudomonas aeruginosa, we screened possible synergistic effects of AGXX on several antibiotic classes. We found that the combination of AGXX and aminoglycosides tested at sublethal concentrations led to a rapid exponential decrease in bacterial survival and restored the sensitivity of a kanamycin-resistant strain. ROS production contributes significantly to the bactericidal effects of AGXX/aminoglycoside treatments, which is dependent on oxygen availability and can be reduced by the addition of ROS scavengers. Additionally, P. aeruginosa strains deficient in ROS detoxifying/repair genes were more susceptible to AGXX/aminoglycoside treatment. We further demonstrate that this synergistic interaction was associated with a significant increase in outer and inner membrane permeability, resulting in increased antibiotic influx. Our study also revealed that AGXX/aminoglycoside-mediated killing requires an active proton motive force across the bacterial membrane. Overall, our findings provide an understanding of cellular targets that could be inhibited to increase the activity of conventional antimicrobials. IMPORTANCE The emergence of drug-resistant bacteria coupled with the decline in antibiotic development highlights the need for novel alternatives. Thus, new strategies aimed at repurposing conventional antibiotics have gained significant interest. The necessity of these interventions is evident especially in gram-negative pathogens as they are particularly difficult to treat due to their outer membrane. This study highlights the effectiveness of the antimicrobial AGXX in potentiating aminoglycoside activities against P. aeruginosa. The combination of AGXX and aminoglycosides not only reduces bacterial survival rapidly but also significantly re-sensitizes aminoglycoside-resistant P. aeruginosa strains. In combination with gentamicin, AGXX induces increased endogenous oxidative stress, membrane damage, and iron-sulfur cluster disruption. These findings emphasize AGXX's potential as a route of antibiotic adjuvant development and shed light on potential targets to enhance aminoglycoside activity.

Antibiograms of field and hospital acquired equine neonatal bacterial fluid cultures in the Midwestern United States: 149 samples (2007‐2018)

Contemporary data reflecting local pathogens and their antibiograms is necessary to select empirical antimicrobial therapy for equine neonates. Describe bacterial isolates associated with equine neonatal infection and their antibiograms in the Midwestern United States. An increase in gram-positive infection and antibiotic resistance compared to previous literature was expected. Data from 149 fluid samples from 133 foals <30 days of age submitted for bacterial culture between January 2007 and December 2018. A retrospective evaluation of equine neonatal fluid cultures was performed. Fluid submission type, bacterial culture and antibiogram, empirical antibiotic treatment, and foal outcome was included. Isolate susceptibility to individual antimicrobials and combination protocols relevant to equine practice were recorded. The effect of recorded variables on foal survival was evaluated using Fisher's exact or chi-squared tests. Ninety bacterial isolates (78 aerobes and 12 anaerobes) were identified and gram-positive organisms predominated (n=50/90, 56%). Greater than 70% of aerobic isolates were susceptible to ampicillin, ceftiofur, chloramphenicol, trimethoprim/sulfamethoxazole, and all penicillin/aminopenicillin and aminoglycoside combinations. Seventy-seven (n=81/105) percent of foals survived. Survival was associated with a negative fluid culture and was not associated with empirical antimicrobial choice. Gram positive and anaerobic isolates associated with equine neonatal fluid cultures exceed that of previous reports. Historical empirical antimicrobial choices for equine neonatal infection in the Midwestern United States are supported by local antibiogram results.

Treatment of Enterococcus faecalis Infective Endocarditis: A Continuing Challenge.

Today, Enterococcus faecalis is one of the main causes of infective endocarditis in the world, generally affecting an elderly and fragile population, with a high mortality rate. Enterococci are partially resistant to many commonly used antimicrobial agents such as penicillin and ampicillin, as well as high-level resistance to most cephalosporins and sometimes carbapenems, because of low-affinity penicillin-binding proteins, that lead to an unacceptable number of therapeutic failures with monotherapy. For many years, the synergistic combination of penicillins and aminoglycosides has been the cornerstone of treatment, but the emergence of strains with high resistance to aminoglycosides led to the search for new alternatives, like dual beta-lactam therapy. The development of multi-drug resistant strains of Enterococcus faecium is a matter of considerable concern due to its probable spread to E. faecalis and have necessitated the search of new guidelines with the combination of daptomycin, fosfomycin or tigecycline. Some of them have scarce clinical experience and others are still under investigation and will be analyzed in this review. In addition, the need for prolonged treatment (6-8 weeks) to avoid relapses has forced to the consideration of other viable options as outpatient parenteral strategies, long-acting administrations with the new lipoglycopeptides (dalbavancin or oritavancin), and sequential oral treatments, which will also be discussed.

Topical Antibiotic Prophylaxis and Intravitreal Injections: Impact on the Incidence of Acute Endophthalmitis-A Nationwide Study in France from 2009 to 2018.

Background: The dramatic increase in intravitreal injections (IVTs) has been accompanied by a greater need for safer procedures. The ongoing debate about topical antibiotic prophylaxis after IVTs emphasizes the importance of large-scale studies. We aimed to study the role of topical antibiotic prophylaxis in reducing the risk of acute endophthalmitis after IVTs. Methods: Population-based cohort study, in France, from 2009 to 2018, including all French patients receiving IVTs of corticosteroids or anti-VEGF agents. Results: A total of 5,291,420 IVTs were performed on 605,434 patients. The rate of topical antibiotic prophylaxis after IVTs progressively decreased during the study period, with a sharp drop in 2014 (from 84.6% in 2009 to 27.4% in 2018). Acute endophthalmitis occurred in 1274 cases (incidence rate = 0.0241%). Although antibiotic prophylaxis did not alter the risk of endophthalmitis (p = 0.06), univariate analysis showed an increased risk after fluoroquinolone and aminoglycoside prophylaxis. This increased risk was not found in multivariate analysis. However, we observed an increased risk related to the use of fixed combinations of fluoroquinolones and aminoglycosides with corticosteroids (IRR = 1.89; 95% CI = 1.57–2.27%, antibiotics combined with corticosteroids). Conclusion: These results are consistent with the literature. Endophthalmitis rates after IVTs did not decrease with topical antibiotic prophylaxis. The use of a combination of antibiotics and corticosteroids doubles the risk of endophthalmitis and should be avoided. Avoiding antibiotic prophylaxis would reduce the costs and the potential risks of antibiotic resistance.

Occurrence and potential transmission of extended-spectrum beta-lactamase-producing extraintestinal pathogenic and enteropathogenic Escherichia coli in domestic dog faeces from Minnesota.

Interactions between humans and pets are increasingly valued in western countries, leading to more extensive contact between humans and their pets within households. Although the magnitude of the risk of transfer of Escherichia coli between humans and their companion animals is undefined, that such transmission occurs has been established and warrants attention. This study examined 186 fresh faecal samples from companion dogs visiting 22 municipal dog parks in the Minneapolis/Saint Paul metropolitan area, Minnesota, USA. Samples were processed to isolate 3rd-generation cephalosporin-resistant E.coli, which were further characterized using PCR-based virulence genotyping, antimicrobial susceptibility profiling and whole-genome sequencing. Of the 186 faecal samples, 29% yielded cephalosporin-resistant E.coli, and 2.2% yielded extended-spectrum beta-lactamase producers. Co-resistance to sulfonamides was typical (77.3% of isolates), and multidrug resistance (i.e. to ≥3 antimicrobial classes), including to combinations of tetracyclines, phenicols, quinolones and aminoglycosides, was substantial (18.9% of isolates). Identified beta-lactamase genes included blaCMY-2 , blaTEM-1B , blaTEM-1 , blaCTX-M-24 , blaCTX-M-15 and blaOXA-1 . Genome sequencing of 14 isolates identified genes typical of extraintestinal pathogenic E.coli or enteropathogenic E.coli. In three instances, closely related isolates were recovered from different dogs, within either the same park-suggesting transfer of E.coli between dogs within the park-or different parks-suggesting that dogs may be pre-disposed to carry certain E.coli types, such as those from serogroups O4, O71 and O157. This study adds to the existing evidence that companion dogs can harbour and share antimicrobial-resistant E.coli with presumed intestinal or extraintestinal pathogenic potential.

Proteomics Study of the Synergistic Killing of Tigecycline in Combination With Aminoglycosides Against Carbapenem-Resistant Klebsiella pneumoniae.

Co-administration of antibiotics with synergistic effects is one method to combat carbapenem-resistant organisms. Although the synergistic effects of tigecycline combined with aminoglycosides against carbapenem-resistant Klebsiella pneumoniae (CRKP) have been demonstrated in vitro and in animal models, the underlying mechanism remains elusive. Here we used proteomics analysis to assess the short-term bacterial responses to tigecycline and aminoglycosides alone or in combination. Emergence of tigecycline resistance during treatment and the susceptibility of tigecycline-resistant strains to aminoglycosides was further evaluated. The proteomic responses to tigecycline and aminoglycosides were divergent in monotherapy, with proteomic alterations to combination therapy dominated by tigecycline. Adaptive responses to tigecycline were associated with the upregulation of oxidative phosphorylation and translation-related proteins. These responses might confer CRKP hypersensitivity towards aminoglycosides by increasing the drug uptake and binding targets. Meanwhile, tigecycline might perturb adaptive responses to aminoglycosides through inhibition of heat shock response. Tigecycline-resistant strains could be isolated within 24 h exposure even in strains without heteroresistance, and the sensitivity to aminoglycosides significantly increased in resistant strains. Overall, these findings demonstrated that adaption to tigecycline in CRKP was a double-edged sword associated with the synergistic killing in tigecycline–aminoglycoside combination. Evolutionary hypersensitivity can provide novel insight into the mechanisms of antibiotic synergistic effects.

Prevalence of High Level Gentamicin Resistance among the Clinical Isolates of Enterococci Species

Enterococci infections, have drawn attention of clinicians due to rapid increase in high level aminoglycoside resistance (HLAR). This resistance predicts failure of β-lactam antibiotic and aminoglycoside combination, which is the current treatment of choice for serious enterococci infections. This led us to investigate about the prevalence of HLAR enterococci in our hospital setting in Shimoga, Karnataka. All the clinical samples received at Microbiology laboratory, McGan hospital, Shivamogga between June 2016 and December 2016 was considered for the study. Enterococci were identified and further speciated by following conventional method. Antibiotic susceptibility pattern of all the isolates was determined according to CLSI guidelines. High level gentamicin resistance was detected by disc diffusion method using 120µg gentamicin disc. A total of 64 Enterococci species were isolated from the clinical specimens. On speciation, Enterococcus faecalis (E. faecalis) accounted for 72% (46) of the total isolates, 24%(16) of the isolates were Enterococcus faecium (E. faecium)and 4% (2) isolates were Enterococcus durans (E. durans). High level gentamicin resistance was noted in 42% (27) among the total isolates. E. faecium was found to be more resistant compared to E. faecalis. E. durans was a sensitive strain. Our study reconfirms the high prevalence of HLAR in the clinical setting. The study stresses on the need for regular screening of HLAR in all Enterococci infections and revise the battery of drugs for its treatment according to the report.

Analysis of diverse β-lactamases presenting high-level resistance in association with OmpK35 and OmpK36 porins in ESBL-producing Klebsiella pneumoniae

Emerging extensively drug-resistant (XDR) Klebsiella pneumoniae due to the production of β-lactamases and porin loss is a substantial worldwide concern. This study aimed to elucidate the role of outer membrane porin (OMP) loss, AmpC, and carbapenemases among extended-spectrum β-lactamase (ESBL)-producing K. pneumoniae strains with XDR phenotype. This study analyzed 79 K. pneumoniae from several clinical sources and detected ESBLs in 29 strains co-harbored with other β-lactamases using standard microbiological practices and phenotypic procedures. Minimum inhibitory concentrations (MICs) were determined against several antibiotics using Microscan WalkAway plus. OMP analysis was carried out using sodium dodecyl sulfate–polyacrylamide gel electrophoresis. ESBL, AmpC, and carbapenemase genes were detected using molecular methods. The microbiological analysis discovered 29 (36.7%) ESBL strains of K. pneumoniae, which showed the co-existence of 7 (24.1%) AmpC β-lactamases and 22 (75.9%) carbapenemases. Porin loss of OmpK35 was observed in 13 (44.8%) and OmpK36 in 8 (27.5%) K. pneumoniae strains. The strains were significantly associated with the intensive care unit (ICU) (p = 0.006) and urinary sources (p = 0.004). The most commonly detected gene variants in each β-lactamase class included 16 (55.2%) blaCTX-M−1, 7 (100%) blaCYM-2, 11 (50%) blaNDM-1, and integron-1 was detected in 21/29 (72.4%) strains. MICs of cephalosporin, fluoroquinolone, carbapenem, aminoglycoside, and β-lactam combinations demonstrated a high number of XDR strains. Tigecycline (2 µg/mL MIC50 and >32 µg/mL MIC90) and colistin (1 µg/mL MIC50 and 8 µg/mL MIC90) presented lower resistance. ESBL K. pneumoniae strains with OmpK35 and OmpK36 porin loss demonstrate conglomerate resistance mechanisms with AmpC and carbapenemases, leading to emerging XDR and pan drug resistance.

Impact of rapid susceptibility testing on antimicrobial therapy and clinical outcomes in Gram-negative bloodstream infections.

Rapid antimicrobial susceptibility testing (rAST) has the potential to improve care of bloodstream infections. The aim of this service evaluation was to assess the impact of rAST on antimicrobial therapy and clinical outcomes in patients with Gram-negative bloodstream infection. A prospective service evaluation was conducted from March 2018 to December 2018. A rAST system (Alfred 60AST) was run Monday-Friday before midday and results were communicated to clinicians on the same day as positive blood culture, with subsequent conventional AST performed. Times to antibiotic therapy and clinical outcomes were compared between rAST and conventional AST. One hundred and ninety-one patients with Gram-negative bacteraemia were included (93 in the rapid group and 98 in the conventional group). Aminoglycoside combination therapy was stopped earlier in the rapid group [32 h (0-795) versus 54 h (4-216), P = 0.002]. The median time to optimal antibiotic based on AST results was significantly shorter than that in the conventional group [50 h (10-339) versus 69.5 h (20-872), P = 0.034]. In the subgroup of patients on ineffective empirical antibiotic, time to effective antibiotic was shorter in the rapid group [39.5 h (32-97) versus 57 h (49-83), P = 0.036]. No differences were found in 28 day mortality or length of stay. Rapid susceptibility testing resulted in faster discontinuation of aminoglycosides and a shorter time to starting effective and optimal antibiotic when compared with conventional AST results. rAST has potential clinical benefits and points to the need for larger future studies in areas of high antibiotic resistance.

Listeria monocytogenes infection during pregnancy

Listeria monocytogenes is an important pathogenic bacteria found in soil or water being the causative agent of listeriosis, a severe foodborne disease during pregnancy. The outcome can lead up to miscarriage, stillbirth, preterm birth and congenital neonatal infections, under occult or overt illness of the mother. We performed a literature review in the medical database PubMed, searching relevant information regarding listeriosis during pregnancy and neonatal outcome. Higher incidences were observed in ethnic minorities, as a reflection of specific dietary habits and where surveillance is not thoroughly implemented. Also, the infection was most commonly seen during the second or third trimester of pregnancy, with maternal presentation under the form of flu-like or pyelonephritis symptoms, or even asymptomatic. Regarding the neonatal infection, there are two types described according to the way of acquiring the bacteria. The obstetric outcome ranges from premature delivery to miscarriage and stillbirth. Treatment of choice is a combination of ampicillin and aminoglycoside. Despite the advances in the field of infectious diseases, challenges remain to completely understand the mechanism of placental invasion of Listeria monocytogenes and the severe consequences on fetal development.

Bacterial infection of fasciotomy wounds following decompression for acute compartment syndrome

Objective: Acute Compartment Syndrome (ACS) is a serious complication generally requiring treatment with an emergency decompressive fasciotomy. The aim of this study was to identify the most prevalent organisms involved in fasciotomy wound infections, and to determine the best strategies to mitigate this risk.Design: Retrospective review.Setting: Single tertiary referral centre.Patients/Participants: Patients (n = 370) who underwent fasciotomy for emergency ACS were included in this study. Positive wound swabs and tissue samples within 30 days post fasciotomy were identified, and extended antibiotic sensitivities were recorded. Patient medical charts were reviewed to assess infection rate, causative organism(s), and clinical outcomes.Intervention: FasciotomyMain Outcome Measurements: Most prevalent organism in fasciotomy wound infections, and the rate of any associated morbidity and mortality.Results: The overall infection rate was 16.7%. Infection rates were significantly higher in burns (27%) and trauma (22%) patients than vascular patients (13%) (p = 0.002). The most prevalent organism was Pseudomonas aeruginosa, isolated from 23% of all wound specimens and comprising over a third (35%) of infections overall. Ten patients required amputation for infection control. Six of these were secondary to Pseudomonas infection, whereby one patient mortality occurred.Conclusion: In this series, one in six fasciotomies for ACS developed an infection within 30 days of their index procedure. Burns and trauma comprised the highest risk groups. Facultative anaerobes were the predominant organisms involved in fasciotomy wound infections. A combination of aminoglycosides and beta-lactams with quinolones should be considered when commencing empiric therapy for fasciotomy wound infections. Antibiotic coverage for routine peri‑operative prophylaxis following emergency decompression for acute compartment syndrome should be strongly considered, particularly in burns or trauma cases.Level of evidence: Aetiologic Level III

Harnessing ultrasound-stimulated phase change contrast agents to improve antibiotic efficacy against methicillin-resistant Staphylococcus aureus biofilms

Bacterial biofilms, often associated with chronic infections, respond poorly to antibiotic therapy and frequently require surgical intervention. Biofilms harbor persister cells, metabolically indolent cells, which are tolerant to most conventional antibiotics. In addition, the biofilm matrix can act as a physical barrier, impeding diffusion of antibiotics. Novel therapeutic approaches frequently improve biofilm killing, but usually fail to achieve eradication. Failure to eradicate the biofilm leads to chronic and relapsing infection, is associated with major financial healthcare costs and significant morbidity and mortality. We address this problem with a two-pronged strategy using 1) antibiotics that target persister cells and 2) ultrasound-stimulated phase-change contrast agents (US-PCCA), which improve antibiotic penetration.We previously demonstrated that rhamnolipids, produced by Pseudomonas aeruginosa, could induce aminoglycoside uptake in gram-positive organisms, leading to persister cell death. We have also shown that US-PCCA can transiently disrupt biological barriers to improve penetration of therapeutic macromolecules. We hypothesized that combining antibiotics which target persister cells with US-PCCA to improve drug penetration could improve treatment of methicillin resistant S. aureus (MRSA) biofilms. Aminoglycosides alone or in combination with US-PCCA displayed limited efficacy against MRSA biofilms. In contrast, the anti-persister combination of rhamnolipids and aminoglycosides combined with US-PCCA dramatically improved biofilm killing. This novel treatment strategy has the potential for rapid clinical translation as the PCCA formulation is a variant of FDA-approved ultrasound contrast agents that are already in clinical practice and the low-pressure ultrasound settings used in our study can be achieved with existing ultrasound hardware at pressures below the FDA set limits for diagnostic imaging.

Coexistence of aminoglycoside resistance genes in CTX-M-producing isolates of Klebsiella pneumoniae in Bushehr province, Iran.

Background and Objectives:Increasing the rate of extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae has given rise to a major healthcare issue in clinical settings over the past few years. Treatment of these strains is hardly effective since the plasmid encoding ESBL may also carry other resistance genes including aminoglycosides. The current study aimed to evaluate the prevalence of ESBL-producing K. pneumoniae and investigate the coexistence of Cefoxitamase-Munich (blaCTX-M) with aminoglycoside-modifying enzyme (AME) genes, aac(3)IIa as well as aac(6′)Ib, in CTX-M-producing K. pneumoniae isolated from patients in Bushehr province, Iran.Materials and Methods:A total of 212 K. pneumoniae isolates were collected and confirmed using polymerase chain reaction (PCR) of the malate dehydrogenase gene. Isolates were screened for production of ESBL. Phenotypic confirmatory test was performed using combined disk test. The genes encoding CTX-M groups and AME genes, aac(3)IIa and aac(6′)Ib, were investigated by PCR.Results:The ESBL phenotype was detected in 56 (26.4%) K. pneumoniae isolates. Moreover, 83.9% of ESBL-producing isolates carried the genes for CTX-M type β-lactamases, which were distributed into the two genetic groups of CTX-M-1 (97.8%)- and CTX-M-2 (2.1%)-related enzymes. Notably, among K. pneumoniae isolates containing the blaCTX-M gene, 68.08% of isolates harbored AME genes. In addition, the coexistence of blaCTX-M with aac(3)-IIa and aac(6′)-Ib was observed in 46.8% of CTX-M-producing K. pneumoniae isolates.Conclusion:This study provides evidence of a high prevalence of AME genes in CTX-M-producing K. pneumoniae isolates; therefore, in the initial empirical treatment of infections caused by ESBL-KP in regions with such antibiotic resistance patterns, aminoglycoside combination therapy should be undertaken carefully.

Prevalence of antibiotic resistance genes among Enterococcus strains isolated from the clinical specimens

BackgroundEnterococci are one of the most common causes of hospital-acquired infections, including urinary tract infections, surgical wound infections, and endocarditis. A combination of aminoglycoside and a cell wall-effective antibiotic such as ampicillin or vancomycin is used to treat serious infections caused by Enterococcus species. Therefore, the resistance of Enterococcus strains to these antibiotics will raise concerns in the treatment of infections caused by these bacteria. MethodsIn this study, Enterococci strains isolated from clinical specimens were identified by biochemical and microbiological methods. PCR technique was used to evaluate the presence of resistance genes to various antibiotics. ResultsA total of 52 Enterococcus strains were identified from clinical specimens and the presence of resistance genes was studied in them. The vanA gene was identified in 11.5% of enterococcal isolates. Both vanA and vanB genes were identified in 3.8% of the isolates, but no vanB and vanC genes were found. The blaZ gene was detected in 9.6% of enterococcal isolates. GyrA and parC fluoroquinolone resistance genes were identified in 86.5% and 88.4% of enterococcal isolates, respectively. The aac (6′)-Ie-aph (2″)-I gene for aminoglycoside acetyltransferase was detected in 30 (57.6%) isolates. ConclusionIn this study, the prevalence of fluoroquinolone resistance genes and aminoglycoside resistance genes were high, so these antibiotics must be prescribed based on antibiogram results. Due to the low prevalence of vancomycin resistance genes and blaZ genes, these antibiotics can be used in the treatment of Enterococcus strains infections.