Combination Of Amikacin Research Articles

Choice of Empirical Treatment in Patients With Wound Infection

Objective: We aimed to determine the distribution of infectious agents in wound culture specimens, their resistance rates, and to evaluate empirical treatment choices in wound infections. Methods: Wound culture results of adult patients between 2016-2020 were retrospectively investigated. Determination of bacteria and antibiotic sensitivity tests were done using conventional methods and automatized systems. Results: A total of 2576 wound specimens were sent, and significant bacterial growth was detected in 1254 (48.7%). Most frequently isolated agent was Escherichia coli (E.coli) (24.2%), followed by Staphylococcus aureus (S.aureus) (16.8%). The highest rate of resistance in Enterobacterales species was against amoxicillin-clavulanate (AMC), except Proteus mirabilis. Antibiotics that Enterobacterales species were most sensitive were amikacin and carbapenems, while it was trimethoprim – sulfamethoxazole (TMP-SXT) for Acinetobacter baumannii, and amikacin for Pseudomonas aeruginosa. The highest rate of resistance in S.aureus strains was against penicillin, with a methicillin resistance rate of 22.9%, while no resistance was found against vancomycin. Conclusion: Initial treatment in wound infections is empirical, and the range of treatment is narrowed when results of culture and sensitivity tests are obtained. Clindamycin, AMC, TMP – SXT and ciprofloxacin seem to be appropriate for outpatients, while TMP-SXT or vancomycin for gram-positive cocci, and TMP-SXT and amikacin combination for gram – negatives, and carbapenems as a last resort.

The renoprotective activity of amikacin–gamma-amino butyric acid–chitosan nanoparticles: a comparative study

The development of nanoparticles (NPs) with active components with upgraded stability, and prolonged release helps in enhanced tissue regeneration. In addition, NPs are feasible strategy to boost antibiotic effectiveness and reduce drug side effects. Our study focuses on the use of amikacin (AMK) and gamma amino butyric acid (GABA) unloaded combinations or loaded on chitosan nanoparticles (CSNPs) for kidney protection. The AMK–GABA–CSNPs were prepared with the ionic gelation method, the morphology was studied using transmission electron microscopy (TEM), zetasizer and the Fourier transform-infrared spectroscopy (FT-IR) spectrum of the synthesized NPs was observed. The average size of AMK–GABA–CSNPs was 77.5 ± 16.5 nm. Zeta potential was + 38.94 ± 2.65 mV. AMK–GABA–CSNPs revealed significant in vitro antioxidant, anti-coagulation, non-hemolytic properties and good cell compatibility. To compare the effects of the unloaded AMK–GABA combination and AMK–GABA–CSNPs on the renal tissue, 42 healthy Sprague–Dawley rats were divided into seven groups. G1: normal control (NC), normal saline; G2: low-dose nephrotoxic group (LDN), AMK (20 mg/kg/day; i.p.); G3: unloaded AMK (20 mg/kg/day; i.p.) and GABA (50 mg/kg/day; i.p.); G4: AMK–GABA–CSNPs (20 mg/kg/day; i.p.); G5: high-dose nephrotoxic group (HDN), AMK (30 mg/kg/day; i.p.); G6: unloaded AMK (30 mg/kg/day; i.p.) and GABA (50 mg/kg/day; i.p.) and G7: AMK–GABA–CSNPs (30 mg/kg/day; i.p.). The results showed that AMK–GABA–CSNPs formulation is superior to unloaded AMK–GABA combination as it ameliorated kidney functions, oxidative stress and displayed a significant homeostatic role via suppression of inflammatory cytokines of Th1, Th2 and Th17 types. Hence, AMK–GABA–CSNPs could afford a potential nano-based therapeutic formula for the management of AMK-nephrotoxicity.

D-histidine combated biofilm formation and enhanced the effect of amikacin against Pseudomonas aeruginosa in vitro

Pseudomonas aeruginosa is an opportunistic gram-negative pathogenic microorganism that poses a significant challenge in clinical treatment. Antibiotics exhibit limited efficacy against mature biofilm, culminating in an increase in the number of antibiotic-resistant strains. Therefore, novel strategies are essential to enhance the effectiveness of antibiotics against Pseudomonas aeruginosa biofilms. D-histidine has been previously identified as a prospective anti-biofilm agent. However, limited attention has been directed towards its impact on Pseudomonas aeruginosa. Therefore, this study was undertaken to explore the effect of D-histidine on Pseudomonas aeruginosa in vitro. Our results demonstrated that D-histidine downregulated the mRNA expression of virulence and quorum sensing (QS)-associated genes in Pseudomonas aeruginosa PAO1 without affecting bacterial growth. Swarming and swimming motility tests revealed that D-histidine significantly reduced the motility and pathogenicity of PAO1. Moreover, crystal violet staining and confocal laser scanning microscopy demonstrated that D-histidine inhibited biofilm formation and triggered the disassembly of mature biofilms. Notably, D-histidine increased the susceptibility of PAO1 to amikacin compared to that in the amikacin-alone group. These findings underscore the efficacy of D-histidine in combating Pseudomonas aeruginosa by reducing biofilm formation and increasing biofilm disassembly. Moreover, the combination of amikacin and D-histidine induced a synergistic effect against Pseudomonas aeruginosa biofilms, suggesting the potential utility of D-histidine as a preventive strategy against biofilm-associated infections caused by Pseudomonas aeruginosa.

The Microbiological Profile and Antibiotic Susceptibility of Fracture Related Infections in a Low Resource Setting Differ from High Resource Settings: A Cohort Study from Cameroon.

Fracture-related infection (FRI) is a common and devastating complication of orthopedic trauma in all settings. Data on the microbiological profile and susceptibility of FRI to antibiotics in low-income countries are scarce. Therefore, this study aimed to investigate the microbial patterns and antimicrobial susceptibility of FRI in a sub-Saharan African setting in order to provide guidance for the formulation of evidence-based empirical antimicrobial regimens. We conducted a retrospective analysis of patients treated for FRI with deep tissue sampling for microbiological culture from January 2016 to August 2023 in four tertiary-level hospitals in Yaoundé, Cameroon. There were 246 infection episodes in 217 patients. Cultures were positive in 209 (84.9%) cases and polymicrobial in 109 (44.3%) cases. A total of 363 microorganisms from 71 different species were identified, of which 239 (65.8%) were Gram-negative. The most commonly isolated pathogens were Staphylococcus aureus (n = 69; 19%), Enterobacter cloacae (n = 43; 11.8%), Klebsiella pneumoniae (n = 35; 9.6%), Escherichia coli (n = 35; 9.6%), and Pseudomonas aeruginosa (n = 27; 7.4%). Coagulase-negative staphylococci (CoNS) were isolated in only 21 (5.9%) cases. Gram-negative bacteria accounted for the majority of the infections in early (70.9%) and delayed (73.2%) FRI, but Gram-positive bacteria were prevalent in late FRI (51.7%) (p < 0.001). Polymicrobial infections were more frequent in the early (55.9%) and delayed (41.9%) groups than in the late group (27.6%) (p < 0.001). Apart from Staphylococcus aureus, there was no significant difference in the proportions of causative pathogens between early, delayed, and late FRI. This study found striking resistance rates of bacteria to commonly used antibiotics. MRSA accounted for 63% of cases. The most effective antibiotics for all Gram-positive bacteria were linezolid (96.4%), vancomycin (92.5%), clindamycin (85.3%), and fucidic acid (89.4%). For Gram-negative bacteria, only three antibiotics displayed a sensitivity >50%: amikacin (80.4%), imipenem (74.4%), and piperacillin + tazobactam (57%). The most effective empirical antibiotic therapy (with local availability) was the combination of vancomycin and amikacin or vancomycin and imipenem. In contrast to the literature from high-resource settings, this study revealed that in a sub-Saharan African context, Gram-negative bacteria are the most common causative microorganisms of FRI. This study revealed striking resistance rates to commonly used antibiotics, which will require urgent action to prevent antimicrobial resistance in low and middle-income countries.

Antibiotic Susceptibility Pattern of Nosocomial and Community-Acquired Pseudomonas aeruginosa in Isfahan: A Prospective Multicenter Study

Background: Pseudomonas aeruginosa is a ubiquitous bacillus responsible for severe infections in inpatients, especially nosocomial and intensive care unit (ICU) infections. Objectives: This study aimed to determine the antibiotic susceptibility of clinical isolates from inpatients in three referral hospitals in Isfahan, Iran. Methods: Standard tests identified the organism and antibiotic susceptibility testing. Stratification was performed by place of infection (community, hospital), admission ward (ICU, non-ICU), and age group (&lt; 20 versus &gt; 20 years). Results: Pseudomonas aeruginosa showed high susceptibility to colistin (100%) and amikacin (81.8%) followed by tobramycin (69.2%), ciprofloxacin (68.5%), meropenem (67.2%), cefepime (65.7%), ceftazidime (64.3%), and imipenem (63.3%). Community-acquired strains were significantly more susceptible to meropenem (81.6%), ciprofloxacin (77.1%), cefepime (77.1%), imipenem (74.3%), and ceftazidime (72.2%) than nosocomial strains. Non-ICU isolates were more susceptible to carbapenems. Pseudomonas aeruginosa isolates had higher antibiotic susceptibility in less than 20 years. Conclusions: Based on the results, a combination of colistin and amikacin would be appropriate for the empiric treatment of suspected P. aeruginosa infections in severe cases, nosocomial infections, or patients admitted to ICU. Ceftazidime, cefepime, ciprofloxacin, meropenem, or imipenem would be suitable for mild to moderate infections, especially in community-acquired infections.

Demography, Clinical Features and Outcome of Bacterial Keratitis Presenting in Tertiary Eye Care in Nepal

Background and Objectives: Bacterial keratitis is an important cause of ocular morbidity in developing country like Nepal and this warrants a detail study of it including its outcome.&#x0D; Material and Methods: Data of demography, clinical features and risk factors of bacterial keratitis were segregated from our previous cross-sectional study of microbial keratitis and retrospective data of treatment and outcome were taken from electronic medical record.&#x0D; Results: Among 123 cases of bacterial keratitis, 111 had bacteria isolated in the culture whereas 12 had bacteria seen only in Gram stain. Average age of patients was 52.6 years; 65(52.8%) were female; 68.3% of total subjects were farmers. Patients had visited the tertiary hospital at an average of 12.9 days since onset of symptoms. Of culture isolates, 55 were Streptococcus pneumonia followed by Staphylococcus aureus (n­­=25) and Streptococcus viridians (n=14). Regarding clinical characteristics, 78(63.4%) cases had hypopyon; 24.3% (n=30) had infiltrate size of &gt;¼ of corneal surface; 16(13.0%) were either perforated or impending to perforate at presentation. Trauma was the main risk factor in 35% (n=43), followed by topical steroid (19.5%, n=24) and dacryocystitis (16.2%, n=20). Patients were treated with combination of fortified cefazoline and amikacin or monotherapy with moxifloxacin or ofloxacin. Overall, 90(73.2%) responded to medical treatment, 19(15.4%) underwent therapeutic penetrating keratoplasty and 3(2.4%) needed evisceration. Smaller sized ulcers had better healing rates (81%) with statistical significance.&#x0D; Conclusion: Patients with bacterial ulcers present late in tertiary eye center causing increased morbidity and even loss of eyes. Awareness, protective measures from trauma and proper treatment has to be undertaken for controlling its occurrence and for better prognosis of the ulcers.

Mortality rate and factors associated with mortality of carbapenem-resistant Enterobacteriaceae infection.

Background: Carbapenem-resistant Enterobacteriaceae (CRE) is a serious pathogen with high mortality. Recognition of factors associated with mortality and treating these modifiable factors are crucial to reducing mortality.Objective: To determine the 30-day mortality and factors associated with a 30-day mortality of CRE infection.Methods: A retrospective cohort study was conducted between January 1, 2015, and December 31, 2019. All patients diagnosed with CRE infection aged ≥18 years were included. Multivariate logistic regression was used for evaluating the factors associated with 30-day mortality and presented as adjusted odds ratio (aOR) with 95% confidence interval (CI).Result: One hundred and ninety-four patients were enrolled. The 30-day mortality occurred in 75 patients (38.7%). The common antibiotic regimen was monotherapy and combination of carbapenem, colistin, amikacin, tigecycline, and fosfomycin. CRE isolates were susceptible to tigecycline (93.8%), colistin (91.8%), fosfomycin (89.2%), and amikacin (89.2%). The independent factors associated with 30-day mortality were an increasing simplified acute physiology (SAP) II score (aOR 1.11, 95% CI 1.05-1.16, p &lt; 0.001), sepsis at time of CRE infection diagnosis (aOR 7.93, 95% CI 2.21-28.51, p = 0.002), pneumonia (aOR 4.48, 95% CI 1.61-12.44, p = 0.004), monotherapy (aOR 4.69, 95% CI 1.71-12.85, p = 0.003), and improper empiric antibiotic (aOR 5.13, 95% CI 1.83-14.40, p = 0.002).Conclusion: The overall 30-day mortality of CRE infection was high. The factors associated with mortality were an increasing SAP II score, sepsis at time of CRE infection diagnosis, pneumonia, monotherapy, and improper empiric antibiotic. The study suggested that proper empiric antibiotic and combination antibiotics might reduce mortality from CRE infection.

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.

Synergy between amikacin and Protium heptaphyllum essential oil against polymyxin resistance Klebsiella pneumoniae.

We investigated the chemical composition and the in vitro and in vivo antibacterial effects of Protium heptaphyllum essential oil (PHEO) alone and in combination with antibiotics against polymyxin-resistant Klebsiella pneumoniae isolates. Hydrodistillation was used to obtain PHEO, and gas chromatography coupled with mass spectrometry revealed α-pinene, δ-3-carene, and β-pinene as major components present in PHEO. Minimum inhibitory concentration was determined using the broth microdilution technique and ranged from 256 to 512µg ml-1. The checkerboard method showed synergy with the combination of PHEO and amikacin (AMK) against the polymyxin-resistant K. pneumoniae isolates. In 8 of the 10 isolates tested, the fractional inhibitory concentration indexes (FICIs) ranged from 0.06 to 0.5, while in the remaining two isolates, the combination exerted an additive effect (FICI of 0.6 and 1.0), resulting in AMK dose reduce of range 2- to 16-fold, in the presence of PHEO. Analysis using zero interaction potency revealed high synergy score (63.9). In the in vivo assay, the survival of Caenorhabditis elegans was significantly improved in the presence of PHEO (1µg ml-1) + AMK (µg ml-1) combination as compared to 32µg ml-1 AMK alone. Furthermore, PHEO concentrations of 256 and 512µg ml-1 were found to be non-toxic on the experimental model. To our knowledge, this is the first report of such type of synergism demonstrating an antimicrobial effect against polymyxin-resistant K. pneumoniae isolates.

CpxA/R-Controlled Nitroreductase Expression as Target for Combinatorial Therapy against Uropathogens by Promoting Reactive Oxygen Species Generation.

The antibiotic resistances emerged in uropathogens lead to accumulative treatment failure and recurrent episodes of urinary tract infection (UTI), necessitating more innovative therapeutics to curb UTI before systematic infection. In the current study, the combination of amikacin and nitrofurantoin is found to synergistically eradicate Gram-negative uropathogens in vitro and in vivo. The mechanistic analysis demonstrates that the amikacin, as an aminoglycoside, induced bacterial envelope stress by introducing mistranslated proteins, thereby constitutively activating the cpxA/R two-component system (Cpx signaling). The activation of Cpx signaling stimulates the expression of bacterial major nitroreductases (nfsA/nfsB) through soxS/marA regulons. As a result, the CpxA/R-dependent nitroreductases overexpression generates considerable quantity of lethal reactive intermediates via nitroreduction and promotes the prodrug activation of nitrofurantoin. As such, these actions together disrupt the bacterial cellular redox balance with excessively-produced reactive oxygen species (ROS) as "Domino effect", accelerating the clearance of uropathogens. Although aminoglycosides are used as proof-of-principle to elucidate the mechanism, the synergy between nitrofurantoin is generally applicable to other Cpx stimuli. To summarize, this study highlights the potential of aminoglycoside-nitrofurantoin combination to replenish the arsenal against recurrent Gram-negative uropathogens and shed light on the Cpx signaling-controlled nitroreductase as a potential target to manipulate the antibiotic susceptibility.

Metabolomics revealed mechanism for the synergistic effect of sulbactam, polymyxin-B and amikacin combination against Acinetobacter baumannii.

The emergence of multidrug-resistant (MDR) Acinetobacter baumannii prompts clinicians to consider treating these infections with polymyxin combination. Metabolomic analysis was applied to investigate the synergistic effects of polymyxin-B, amikacin and sulbactam combination therapy against MDR A. baumannii harboring OXA-23 and other drug resistant genes. The drug concentrations tested were based on their clinical breakpoints: polymyxin-B (2 mg/L), amikacin (16 mg/L), polymyxin-B/amikacin (2/16 mg/L), and polymyxin-B/amikacin/sulbactam (2/16/4 mg/L). The triple antibiotic combination significantly disrupted levels of metabolites involved in cell outer membrane structure including fatty acids, glycerophospholipids, nucleotides, amino acids and peptides as early as 15 min after administration. Amikacin and polymyxin-B alone perturbed a large number of metabolites at 15 min and 1 h, respectively, but the changes in metabolites were short-lived lasting for less than 4 h. In contrast, the combination treatment disrupted a large amount of metabolites beyond 4 h. Compared to the double-combination, the addition of sulbactam to polymyxin-B/amikacin combination produce a greater disorder in A. baumannii metabolome that further confer susceptibility of bacteria to the antibiotics. The metabolomic analysis identified mechanisms responsible for the synergistic activities of polymyxin-B/amikacin/sulbactam against MDR A. baumannii.

Treatment of Colistin Dependence-Developing Acinetobacter baumannii with Antibiotic Combinations at Subinhibitory Concentrations.

Recent studies have revealed that colistin dependence frequently develops in colistin-susceptible Acinetobacter baumannii isolates. Despite resistance in parental strains, colistin-dependent mutants showed increased susceptibility to several antibiotics, which suggests the possibility of developing strategies to eliminate multidrug-resistant (MDR) A. baumannii. We investigated in vitro and in vivo efficacy of combinations of colistin and other antibiotics using MDR A. baumannii strains H08-391, H06-855, and H09-94, which are colistin-susceptible but develops colistin dependence upon exposure to colistin. An in vitro time-killing assay, a checkerboard assay, and an antibiotic treatment assay using Galleria mellonella larvae were performed. Although a single treatment of colistin at a high concentration did not prevent colistin dependence, combinations of colistin with other antibiotics at subinhibitory concentrations, especially amikacin, eradicated the strains by inhibiting the development of colistin dependence, in the in vitro time-killing assay. Only 40% of G. mellonella larvae infected by A. baumannii survived with colistin treatment alone; however, all or most of them survived following treatment with the combination of colistin and other antibiotics (amikacin, ceftriaxone, and tetracycline). Our results suggest the possibility of the combination of colistin and amikacin or other antibiotics as one of therapeutic options against A. baumannii infections by eliminating colistin-dependent mutants.

The synergetic effect of sitafloxacin–arbekacin combination in the Mycobacterium abscessus species

Mycobacterium abscessus species (MABS) is the most commonly isolated rapidly growing mycobacteria (RGM) and is one of the most antibiotic-resistant RGM with rapid progression, therefore, treatment of MABS is still challenging. We here presented a new combination treatment with sitafloxacin that targeted rough morphotypes of MABS, causing aggressive infections. Thirty-four clinical strains of MABS were isolated from various clinical samples at the Juntendo university hospital from 2011 to 2020. The susceptibility to a combination of sitafloxacin and antimicrobial agents was compared to that of the antimicrobial agents alone. Out of 34 MABS, 8 strains treated with sitafloxacin–amikacin combination, 9 of sitafloxacin–imipenem combination, 19 of sitafloxacin–arbekacin combination, and 9 of sitafloxacin–clarithromycin combination showed synergistic effects, respectively. Sitafloxacin–arbekacin combination also exhibited the synergistic effects against 10 of 22 Mycobacterium abscessus subspecies massiliense (Mma) strains and 8 of 11 Mycobacterium abscessus subspecies abscessus (Mab) strains, a highly resistant subspecies of MABS. The sitafloxacin–arbekacin combination revealed more synergistic effects in rough morphotypes of MABS (p = 0.008). We demonstrated the synergistic effect of the sitafloxacin–arbekacin combination against MABS. Further, this combination regimen might be more effective against Mab or rough morphotypes of MABS.

Antibiotic-Potentiating Effect of Some Bioactive Natural Products against Planktonic Cells, Biofilms, and Virulence Factors of Pseudomonas aeruginosa.

Pseudomonas aeruginosa is an opportunistic human pathogen that causes infections that are mediated by both virulence factor production and biofilm formation. In addition, many antibiotics are increasingly losing their efficacy due to the development of resistance. The screening of potentially bioactive natural compounds that have both antivirulence and antibiofilm activities to enhance antibiotic efficacy and reverse antibiotic resistance is a good strategy to overcome these issues. In this study, the antibacterial, antibiofilm, and antivirulence factor activities of some bioactive natural products in combination with conventional antibiotics were evaluated against clinical isolates of P. aeruginosa. The broth microdilution method was used to determine the antibacterial and antibiofilm activities. The checkerboard method was used to evaluate the combination interactions. Spectrophotometric and agar plate techniques were used to assess the effect of the combination on the pyocyanin production and the motility in P. aeruginosa ATCC 27853 strain. Out of the eighteen combinations tested, ten exhibited synergistic effects against planktonic cells, seven against biofilm inhibition, and five against the eradication of mature biofilm of P. aeruginosa biofilm. The best synergistic effect was the association of amikacin and sinapic acid against planktonic cells (FICI = 0.08) with a 70-fold reduction in the MIC value of amikacin. The same combination showed significant synergistic inhibition of biofilm formation (FICI = 0.1) and biofilm eradication (FICI = 0.15) reducing the MBIC and MBEC of amikacin by 32-fold. Some selected synergistic combinations showed statistically significant differences (p < 0.01 or p < 0.001) in the inhibition of virulence factors compared to the antimicrobials alone. In summary, this study revealed sinapic acid as an antibiotic adjuvant and antivirulence compound to overcome P. aeruginosa infections. This finding indicates that the combinations of amikacin plus sinapic acid, ceftazidime plus thymol, and norfloxacin plus curcumin could be considered promising candidates for the development of combination therapies targeting virulence factors against P. aeruginosa infections.

MYCOBACTERIUM HAEMOPHILUM AND CRYPTOCOCCUS NEOFORMANS COINFECTION IN A SYSTEMIC LUPUS ERYTHEMATOSUS PATIENT

Mycobacterium haemophilum and Cryptococcus neoformans are human pathogens in immunocompromised individuals. They exhibit a diversity of cutaneous manifestations and could cause disseminated infections. Herein, we report a Thai female with an underlying disease of systemic lupus erythematous, end stage renal disease and hypertension who was on immunosuppressive therapy and diagnosed with disseminated M. haemophilum and C. neoformans coinfection. She presented with multiple indurated plaques on her back, oedematous plaques on both legs and feet with nodules and ulcers on her right leg. She was diagnosed by skin biopsy, acid-fast staining, real-time polymerase chain reaction, tissue culture and haemoculture. A combination of rifampicin, macrolide, fluoroquinolone, amikacin and co-trimoxazole were used to cure M. haemophilum infection. Cryptococcosis was treated with amphotericin B and flucytosine for 5 weeks, then followed by fluconazole. We aim to report a unique dermatological manifestation, microbiology, histopathology, and treatment of the disease. Successful diagnosis and multiple antimicrobials agents are key managements for Mycobacterium haemophilum infection and Cryptococcosis.

Effects of amikacin, polymyxin-B, and sulbactam combination on the pharmacodynamic indices of mutant selection against multi-drug resistant Acinetobacter baumannii.

Amikacin and polymyxins as monotherapies are ineffective against multidrug-resistant Acinetobacter baumannii at the clinical dose. When polymyxins, aminoglycosides, and sulbactam are co-administered, the combinations exhibit in vitro synergistic activities. The minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC) were determined in 11 and 5 clinical resistant isolates of A. baumannii harboring OXA-23, respectively, in order to derive the fraction of time over the 24-h wherein the free drug concentration was within the mutant selection window (fTMSW) and the fraction of time that the free drug concentration was above the MPC (fT>MPC) from simulated pharmacokinetic profiles. The combination of these three antibiotics can confer susceptibility in multi-drug resistant A. baumannii and reduce the opportunity for bacteria to develop further resistance. Clinical intravenous dosing regimens of amikacin, polymyxin-B, and sulbactam were predicted to optimize fTMSW and fT>MPC from drug exposures in the blood. Mean fT>MPC were ≥ 60% and ≥ 80% for amikacin and polymyxin-B, whereas mean fTMSW was reduced to <30% and <15%, respectively, in the triple antibiotic combination. Due to the low free drug concentration of amikacin and polymyxin-B simulated in the epithelial lining fluid, the two predicted pharmacodynamic parameters in the lung after intravenous administration were not optimal even in the combination therapy setting.

In Vitro and In Vivo Effect of Amikacin and Imipenem Combinations against Multidrug-Resistant E. coli.

Introduction: The emergence of multidrug-resistant (MDR) E. coli has developed worldwide; therefore, the use of antibiotic combinations may be an effective strategy to target resistant bacteria and fight life-threatening infections. The current study was performed to evaluate the in vitro and in vivo efficacy of amikacin and imipenem alone and in combination against multidrug-resistant E. coli. Methods: The combination treatment was assessed in vitro using a checkerboard technique and time-killing curve and in vivo using a peritonitis mouse model. In resistant isolates, conventional PCR and quantitative real-time PCR techniques were used to detect the resistant genes of Metallo-β-lactamase gene Imipenemase (bla-IMP) and aminoglycoside 6′-N-acetyltransferase (aac (6′)-Ib). Scanning electron microscopy was used to detect the morphological changes in the resistant isolates after treatment with each drug alone and in combination. In vitro and in vivo studies showed a synergistic effect using the tested antibiotic combinations, showing fractional inhibitory concentration indices (FICIs) of ≤0.5. Regarding the in vivo study, combination therapy indicated a bactericidal effect after 24 h. E. coli isolates harboring the resistant genes Metallo-β-lactamase gene Imipenemase (bla-IMP) and aminoglycoside 6′-N-acetyltransferase (aac (6′)-Ib) represented 80% and 66.7%, respectively, which were mainly isolated from wound infections. The lowest effect on Metallo-β-lactamase gene Imipenemase (bla-IMP) and aminoglycoside 6′-N-acetyltransferase (aac (6′)-Ib) gene expression was shown in the presence of 0.25 × MIC of imipenem and 0.5 × MIC of amikacin. The scanning electron microscopy showed cell shrinkage and disruption in the outer membrane of E. coli in the presence of the antibiotic combination. Amikacin and imipenem combination can be expected to be effective in the treatment and control of serious infections caused by multidrug-resistant (MDR) E. coli and the reduction in bacterial resistance emergence.

Assessment of flomoxef combined with amikacin in a hollow-fibre infection model for the treatment of neonatal sepsis in low- and middle-income healthcare settings.

Annual mortality from neonatal sepsis is an estimated 430 000-680 000 infants globally, most of which occur in low- and middle-income countries (LMICs). The WHO currently recommends a narrow-spectrum β-lactam (e.g. ampicillin) and gentamicin as first-line empirical therapy. However, available epidemiological data demonstrate high rates of resistance to both agents. Alternative empirical regimens are needed. Flomoxef and amikacin are two off-patent antibiotics with potential for use in this setting. To assess the pharmacodynamics of flomoxef and amikacin in combination. The pharmacodynamic interaction of flomoxef and amikacin was assessed in chequerboard assays and a 16-arm dose-ranged hollow-fibre infection model (HFIM) experiment. The combination was further assessed in HFIM experiments mimicking neonatal plasma exposures of clinically relevant doses of both drugs against five Enterobacterales isolates with a range of flomoxef/amikacin MICs. Flomoxef and amikacin in combination were synergistic in bacterial killing in both assays and prevention of emergence of amikacin resistance in the HFIM. In the HFIM assessing neonatal-like drug exposures, the combination killed 3/5 strains to sterility, (including 2/5 that monotherapy with either drug failed to kill) and failed to kill the 2/5 strains with flomoxef MICs of 32 mg/L. We conclude that the combination of flomoxef and amikacin is synergistic and is a potentially clinically effective regimen for the empirical treatment of neonatal sepsis in LMIC settings and is therefore suitable for further assessment in a clinical trial.

Once-a-Day Ceftriaxone-Amikacin Combination as Empiric Antibiotic Therapy to Enable Outpatient Management of Febrile Neutropenia in Children-16-Year Experience from a Single Institute.

Shailesh KanvindeBackground To enable outpatient department (OPD) management of febrile neutropenia (FN), we used once-a-day (OD) ceftriaxone-amikacin (CFT-AMK) as empiric antibiotic therapy. Our experience over 16-year period is presented. Methods This was a retrospective study conducted from January2002 to December2017. Inclusion criteria were <18 years of age, undergoing cancer chemotherapy, and having FN. Exclusion criteria were FN after palliative chemotherapy, bone marrow transplantation, or at diagnosis of malignancy. Empiric CFT-AMK was used in all, except those having respiratory distress, hypotension, altered sensorium, paralytic ileus, or clinical evidence of peritonitis. Admission criteria were age <1 year, acute myeloid leukemia (AML) chemotherapy, poor performance status, need for blood transfusions, convenience, insurance, or persistent fever >48 to 72 hours after CFT-AMK. Outcomes analyzed were response (defervescence within 48-72 hours), OPD management, antibiotic upgrade, and mortality. AML diagnosis, >7 days to absolute neutrophil count >0.5 × 10 9 /L, poor performance status, and malignancy not in remission were considered high-risk FN criteria. Results CFT-AMK was given in 877/952 (92.2%) FN episodes. Seventy-six percent had hematolymphoid malignancies. Response, antibiotic upgrade, and mortality were seen in 85.7 and 65.5% ( p < 0.0001), 15 and 45.5% ( p < 0.0001), and 0 and 2% ( p = 0.003) of low- and high-risk patients, respectively. Treatment was started in OPD in 52%, of which 21.6% required subsequent admission. Of those initially admitted, early discharge (hospital stay < 5 days) was possible in 24.6%. Forty-one percent episodes were managed entirely on OPD. Overall, 80% of low-risk and 42% of high-risk episodes received treatment wholly or partially on OPD. Conclusion Our results show empiric OD CFT-AMK allows OPD management for most of the low-risk and a proportion of high-risk FN following chemotherapy in children, without compromising clinical outcomes.

Bacteriological profile and antibiotics sensitivity patterns among neonates admitted at Birat Medical College Teaching Hospital

Background: Neonatal sepsis still remains serious and potentially life-threatening events with a mortality rate of up to 50%. The current practice of starting empirical antibiotic therapy in all neonates showing infection-like symptoms results in their exposure to adverse drug effects, nosocomial complications, and in the emergence of resistant strains. The antibiotic sensitivity pattern of organisms is changing very rapidly over a short period which is varying from country to country, one place to another, and one institute to another. Therefore, periodic evaluation of sensitivity patterns is essential for rational and appropriate use of antibiotics. Aims and Objectives: This study aims to see bacteriological profile and their antibiotics sensitivity among the sepsis suspected neonates at the neonatal intensive care unit of Birat Medical College Teaching Hospital (BMCTH). Materials and Methods: It was a cross-sectional descriptive study from July 21, 2021, to December 21, 2021. Sample size of 138 was included in the study. Neonates were selected by non-probability consecutive sampling techniques. Neonatal sepsis suspected neonates and plan to treat with injectable antibiotics by the treating pediatrician were included in the study. All patients included were started on empirical antibiotics after drawing samples for blood cultures and CRP along with other investigations. Bacteriological profile and their sensitivity to different antibiotics were collected from blood culture reports. Data collection was done using a specifically designed questionnaire. The descriptive and inferential statistics were used for data analysis. The test of significance was done by the Chi-square test. P&lt;0.05 was considered statistically significant. Results: Among the 46 blood culture-proven sepsis, the most common organism isolated was Staphylococcus aureus which was 33 (71.7%). Among the isolated S. aureus, 100% were sensitive to colistin sulfate and injectable linezolid, 93.1% sensitive to injectable meropenem, 85.7% sensitive to injectable piperacillin and tazobactam combination, 83.3% sensitive to injectable vancomycin, and 85.7% sensitive to injectable amikacin but only 40.7% to injectable cefotaxime. Isolated Acinetobacter species were found 100% sensitive to colistin sulfate and meropenem, and 80% sensitive to cefotaxime and amikacin but only 66.7% sensitive to injectable piperacillin and tazobactam combination. Only one neonate had Klebsiella isolated in blood culture which was 100% resistant to injectable cefotaxime but was sensitive 100% to Meropenem, piperacillin-tazobactam, and amikacin. Isolated Enterococcus species were 100% sensitive to piperacillin-tazobactam combination, meropenem, and imipenem but only 66.7% sensitive to injectable cefotaxime. Conclusion: Gram-positive isolates were the predominant pathogens among enrolled neonatal sepsis suspected neonates at Birat medical college teaching hospital (BMCTH). Based on our findings, a combination of cefotaxime and amikacin can be used as first-line therapy. However, cefotaxime only had moderate sensitivity, so change to piperacillin-tazobactam and vancomycin or linezolid as second-line therapy can be considered early in case of no improvement or deterioration, or combination of vancomycin and meropenem as third line would be the appropriate empirical therapy at BMCTH. However, the use of the broad-spectrum antibiotics as empirical therapy should be evaluated in the long run and should be used cautiously and modified to narrow spectrum antibiotics, as guided by the culture and susceptibility report at the earliest possible.