BACKGROUND

Infections of the central nervous system may develop in patients with traumatic brain injury after the implant of external ventricular drainage catheters or after neurological surgeries.

We report the case of a woman in her 50s who was admitted with a subarachnoid hemorrhage secondary to a ruptured aneurysm, for which she underwent a tube ventriculostomy with an external ventricular drain attached and developed neurosurgical meningitis. The cerebrospinal fluid culture showed the presence of multidrug-resistant Acinetobacter baumannii. Intrathecal delivery of 65,000 units of colistin methyl sodium twice daily with a clamp drain for 15 to 60 min after administration was used as treatment. After 72 hours of treatment, the patient's infection improved, and repeat cerebrospinal fluid culture showed no microbial growth.

Intrathecal colistin can be used as a treatment for multidrug-resistant A. baumannii meningitis.

Background: Multidrug-resistant gram-negative (MDR GN) infections pose a significant threat to pediatric health. One of the treatment options in resource-limited settings is polymyxin-based combination therapy. However, evidence on the safety and clinical effectiveness of polymyxin B in children is scarce. Objectives: This study described the outcomes of mortality, bacteriologic cure and clinical response in pediatric patients with MDR GN infections treated with polymyxin-B-based combination therapy. Adverse drug events (ADE) are likewise described. Methodology: This is a retrospective descriptive study conducted at the Philippine General Hospital (PGH) among pediatric inpatients from December 2020 to June 2023 with MDR GN infections treated with polymyxin B (PmB), combined with at least one other antibiotic with gram-negative coverage for at least 48 hours. Frequency and rates of the outcomes were measured and analyzed, in relation to the bacterial groups (Enterobacterales, Acinetobacter spp., Pseudomonas aeruginosa) and combination antibiotic regimens used, i.e., meropenem- and fluoroquinolone-containing regimen (PmB+MEM vs PmB+FQ). Frequency of ADEs were measured. Results: A total of 172 cases in 136 patients were reviewed. The rates for 14-day mortality, failure in bacteriologic cure, and failure in clinical response were 26%, 15%, and 19%, respectively. In Enterobacterales infections, PmB+FQ demonstrated lower rates of mortality, failure in bacteriologic cure, and failure in clinical responses. On the other hand, in Acinetobacter infections, PmB+MEM numerically had lower rates for the same outcomes. The Pseudomonas group had conflicting data on which regimen is numerically more favorable overall. No statistically significant differences were found in the outcomes. ADEs noted were tubulopathy (5 cases), anaphylaxis (2 cases), and neurotoxicity (1 case). Conclusion Polymyxin-B-based combination therapy appears to be an acceptable treatment option for MDR GN infections in children, especially in settings where novel antibiotics are not accessible. Safety profiles indicate common but manageable adverse effects.
Polymyxin B ; Child

Objective:b> To assess the efficacy and safety of polymyxin B in neutropenic patients with hematologic disorders who had refractory gram-negative bacterial bloodstream infection. Methods:b> From August 2021 to July 2022, we retrospectively analyzed neutropenic patients with refractory gram-negative bacterial bloodstream infection who were treated with polymyxin B in the Department of Hematology of the First Affiliated Hospital of the Soochow University between August 2021 to July 2022. The cumulative response rate was then computed. Results:b> The study included 27 neutropenic patients with refractory gram-negative bacterial bloodstream infections. Polymyxin B therapy was effective in 22 of 27 patients. The median time between the onset of fever and the delivery of polymyxin B was 3 days [interquartile range (IQR) : 2-5]. The median duration of polymyxin B treatment was 7 days (IQR: 5-11). Polymyxin B therapy had a median antipyretic time of 37 h (IQR: 32-70). The incidence of acute renal dysfunction was 14.8% (four out of 27 cases), all classified as "injury" according to RIFLE criteria. The incidence of hyperpigmentation was 59.3%. Conclusion:b> Polymyxin B is a viable treatment option for granulocytopenia patients with refractory gram-negative bacterial bloodstream infections.
Humans ; Polymyxin B/adverse effects* ; Retrospective Studies ; Gram-Negative Bacterial Infections/complications* ; Fever/drug therapy* ; Sepsis/drug therapy* ; Anti-Bacterial Agents/therapeutic use* ; Bacteremia/complications*

Objective:b> To investigate the antimicrobial resistance of food-borne diarrheagenic Escherichia coli (DEC) and the prevalence of mcr genes that mediates mobile colistin resistance in parts of China, 2020. Methods:b> For 91 DEC isolates recovered from food sources collected from Fujian province, Hebei province, Inner Mongolia Autonomous Region and Shanghai city in 2020, Vitek2 Compact biochemical identification and antimicrobial susceptibility testing platform was used for the detection of antimicrobial susceptibility testing (AST) against to 18 kinds of antimicrobial compounds belonging to 9 categories, and multi-polymerase chain reaction (mPCR) was used to detect the mcr-1-mcr-9 genes, then a further AST, whole genome sequencing (WGS) and bioinformatics analysis were platformed for these DEC isolates which were PCR positive for mcr genes. Results:b> Seventy in 91 isolates showed different antimicrobial resistance levels to the drugs tested with a resistance rate of 76.92%. The isolates showed the highest antimicrobial resistance rates to ampicillin (69.23%, 63/91) and trimethoprim-sulfamethoxazole (59.34%, 54/91), respectively. The multiple drug-resistant rate was 47.25% (43/91). Two mcr-1 gene and ESBL (extended-spectrum beta-lactamase) positive EAEC (enteroaggregative Escherichia coli) strains were detected. One of them was identified as serotype of O11:H6, which showed a resistance profile to 25 tested drugs referring to 10 classes, and 38 drug resistance genes were predicted by genome analysis. The other one was O16:H48 serotype, which was resistant to 21 tested drugs belonging to 7 classes and carried a new variant of mcr-1 gene (mcr-1.35). Conclusion:b> An overall high-level antimicrobial resistance was found among foodborne DEC isolates recovered from parts of China in 2020, and so was the MDR (multi-drug resistance) condition. MDR strains carrying multiple resistance genes such as mcr-1 gene were detected, and a new variant of mcr-1 gene was also found. It is necessary to continue with a dynamic monitoring on DEC contamination and an ongoing research into antimicrobial resistance mechanisms.
Humans ; Colistin/pharmacology* ; Anti-Bacterial Agents/pharmacology* ; Escherichia coli Infections/epidemiology* ; Escherichia coli Proteins/genetics* ; Drug Resistance, Bacterial/genetics* ; China/epidemiology* ; Escherichia coli ; Plasmids/genetics* ; Microbial Sensitivity Tests

Objective:b> Analysis and investigation of pathogenic characteristics of polymyxin-and carbapenem-resistant Klebsiella pneumoniae (PR-CRKP). Methods:b> A total of 23 PR-CRKP strains isolated from clinical specimens from the General Hospital of Southern Theater Command from March 2019 to July 2021 were retrospectively collected, Whole-genome sequencing was performed on 23 PR-CRKP strains, resistance genes were identified by comparison of the CARD and the ResFinder database, high-resolution typing of PR-CRKP strains was analyzed by core genomic multilocus sequencing (cgMLST) and single nucleotide polymorphism (SNP); polymyxin resistance genes were determined by PCR and sequencing. Results:b> All PR-CRKP strains were KPC-2 producing ST11 types. cgMLST results showed that the evolutionary distance between the PR-CRKP strains and Klebsiella pneumoniae in mainland China was 66.44 on average, which is more closely related than foreign strains; the 23 PR-CRKP strains were divided into 3 main subclusters based on SNP phylogenetic trees, with some aggregation among Clade 2-1 in the isolation department and date. The two-component negative regulatory gene mgrB has seven mutation types including point mutations, different insertion fragments and different insertion positions. Conclusion:b> The close affinity of PR-CRKP strains indicate the possibility of nosocomial clonal transmission and the need to strengthen surveillance of PR-CRKP strains to prevent epidemic transmission of PR-CRKP.
Humans ; Carbapenems/pharmacology* ; Anti-Bacterial Agents/therapeutic use* ; Klebsiella pneumoniae/genetics* ; Polymyxins/pharmacology* ; beta-Lactamases ; Phylogeny ; Retrospective Studies ; Multilocus Sequence Typing ; Microbial Sensitivity Tests

Polymyxin B, which is a last-line antibiotic for extensively drug-resistant Gram-negative bacterial infections, became available in China in Dec. 2017. As dose adjustments are based solely on clinical experience of risk toxicity, treatment failure, and emergence of resistance, there is an urgent clinical need to perform therapeutic drug monitoring (TDM) to optimize the use of polymyxin B. It is thus necessary to standardize operating procedures to ensure the accuracy of TDM and provide evidence for their rational use. We report a consensus on TDM guidelines for polymyxin B, as endorsed by the Infection and Chemotherapy Committee of the Shanghai Medical Association and the Therapeutic Drug Monitoring Committee of the Chinese Pharmacological Society. The consensus panel was composed of clinicians, pharmacists, and microbiologists from different provinces in China and Australia who made recommendations regarding target concentrations, sample collection, reporting, and explanation of TDM results. The guidelines provide the first-ever consensus on conducting TDM of polymyxin B, and are intended to guide optimal clinical use.
Humans ; Anti-Bacterial Agents/therapeutic use* ; China ; Drug Monitoring/methods* ; Polymyxin B ; Practice Guidelines as Topic

OBJECTIVE: To investigate the efficacy and safety of colistin sulfate in the treatment of hematonosis patients infected by multidrug-resistant (MDR) gram-negative bacteria (GNB), and discuss the possible factors that affect the efficacy of colistin sulfate. METHODS: The clinical data of 85 hematologic patients infected with MDR GNB in the Soochow Hopes Hematonosis Hospital from April 2022 to November 2022 were collected and divided into clinically effective group with 71 cases and ineffective group with 14 cases according to the therapeutic efficacy of colistin sulfate. The age, gender, type of hematologic disease, status of hematopoietic stem cell transplantation, infection sites, type of pathogen, timing of administration, daily dose and duration of colistin sulfate, and combination with other antibacterial agents of patients in two groups were compared. Logistic regression was used to analyze on the meaningful variables to study the influencing factors of colistin sulfate. The adverse reactions of colistin sulfate were also evaluated. RESULTS: There were no significant differences in age, gender, type of hematologic disease, hematopoietic stem cell transplantation status, infection sites and pathogen type between the effective group and the ineffective group (P>0.05). Compared with the medication time more than 7 days, meropenem used within 7 days in the clinical effective group, and timely replacement with colistin sulfate could obtain better efficacy, the difference was statistically significant (P=0.018). The duration of tigacycline before colistin sulfate did not affect the efficacy, and there was no significant difference in efficacy between the effective and ineffective groups. The therapeutic effect of colistin sulfate at daily dose of 500 000 U q8h was better than that of 500 000 U q12h, the difference was statistically significant (P=0.035). The time of colistin sulfate use in the clinically effective group was longer than that in the ineffective group, which had a statistical difference (P=0.003). Compared with the clinical ineffective group, the efficacy of combination regimens with colistin sulfate was better than that of colistin sulfate monotherapy, and the difference was statistically significant (P=0.013). Multivariate logistic regression analysis was performed on the indicators with statistical differences in the two groups of patients, which suggested that the use time of colistin sulfate (B: 2.358; OR: 10.573; CI: 1.567-71.361; P=0.015) and the combination of colistin sulfate (B: 1.720; OR: 5.586; CI: 1.210-25.787; P=0.028) were influential factors in the efficacy of colistin sulfate. During the treatment, the incidence of nephrotoxicity, hepatotoxicity and peripheral neurotoxicity were 5.9%, 1.2% and 1.2%, respectively. CONCLUSION The use of colistin sulfate improves the clinical efficacy of MDR GNB infections in hematological patients, and the timing of colistin sulfate administration and the combination of drugs are independent factors affecting its clinical efficacy, and the safety during treatment is high.
Humans ; Colistin/adverse effects* ; Anti-Bacterial Agents/therapeutic use* ; Meropenem/adverse effects* ; Treatment Outcome ; Gram-Negative Bacteria ; Hematologic Diseases

OBJECTIVE: To observe the clinical efficacy and safety of polymyxin B sulfate in febrile neutropenia patients with hematonosis. METHODS: Clinical data of 50 patients in the department of hematology, Fujian Medical University Union Hospital from October 2019 to September 2020 were collected. All the patients developed febrile neutropenia after chemotherapy or hematopoietic stem cell transplantation. According to the results of drug susceptible test, polymyxin B sulfate was administrated mainly when the empirical antimicrobial treatments was poor and the pathogenic microbes test was positive. RESULTS: A total of 85 times of infection occurred in 50 patients. The infection sites were lung, blood flow, intestinal tract, oral cavity, perianal, soft tissue and nasal cavity. Gram negative bacteria was the main pathogenic microbe. After administration of polymyxin B sulfate when the etiology was confirmed, the total effective rate was 68%, especially the effective rate increased significantly after more than 7 days of polymyxin B sulfate treatment. Also, 24% and 8% of the patients were discharged automatically and died respectively. The effective rate of patients receiving carbapenem antibiotics changed to polymyxin B sulfate within 14 or 7 days was 80% and 70.6%, respectively, while the effective rate of patients who changed after 2 weeks was only 33.3%. The effective rate of patients receiving tigecycline changed to polymyxin B sulfate within 14 or 7 days was 80% and 66.7%, respectively. The incidence of adverse reactions of polymyxin B sulfate was low, most of which were mild, and only one patient occurred rhabdomyolysis. CONCLUSION Polymyxin B sulfate has good clinical efficacy and safety in febrile neutropenia patients with hematonosis.
Anti-Bacterial Agents/therapeutic use* ; Carbapenems ; Febrile Neutropenia/drug therapy* ; Humans ; Polymyxin B/therapeutic use* ; Tigecycline

Aims: Polymyxins are an important last-line treatment for infections caused by multidrug-resistant Gram-negative bacteria. Nonetheless, the emergence of polymyxin-resistance and the limiting of polymyxin monotherapy urgently demands its optimisation. Aquilaria malaccensis (Agarwood) has been widely used as traditional medicine. Many parts of the plant including leaves exhibit a considerable in vitro antibacterial activity against microbial pathogens. Exploiting A. malaccensis in combination with polymyxins provides a novel strategy in fighting antimicrobial resistance. The objective of this study was to evaluate the combination effects of A. malaccensis extract with polymyxins against Acinetobacter baumannii and Klebsiella pneumoniae. Methodology and results: In vitro time-kill studies and GC-MS analysis were performed to evaluate the bacterial killing of polymyxin B and extract combination and analyse chemical compounds of the extract, respectively. The combination of polymyxin B (1 mg/L) and A. malaccensis extract (32 mg/mL and 64 mg/mL) treatments exhibited enhanced bacterial killing compared to polymyxin B alone at 4 h and 24 h. Combination treatments also inhibited the bacterial growth of both A. baumannii and K. pneumoniae observed throughout the 24 h. More than sixty compounds including phytol, 9,12-octadecadienal, fatty acid, alkanes and terpenoids were putatively identified as the compounds that likely contributed to the antibacterial activity. Conclusion, significance and impact of study This study was the first to report the potential application of A. malaccensis extract in combination with polymyxin B in treatment against A. baumannii and K. pneumoniae and can be further investigated and optimized for the treatment of bacterial infectious diseases.
Thymelaeaceae ; Polymyxins ; Acinetobacter baumannii--immunology ; Klebsiella pneumoniae--immunology

The current strategy in treating multi-drug resistant gram-negative bacterial (MDR-GNB) infections is salvage therapy by using polymyxins. However, the beginning emergence of polymyxin resistance should enforce strict antimicrobial stewardship programs to preserve polymyxin efficacy. Knowledge of structural characteristics, pharmacodynamic, and pharmacokinetic profiles of polymyxins, as well as consideration of efficacy, safety, suitability, and cost, will help in the choice of the appropriate polymyxin for therapy. Polymyxin B is the recommended polymyxin for systemic use, while colistin is recommended for lower urinary tract infections, intraventricular, and intrathecal use. Either polymyxin can be used for hospital-acquired and ventilator-associated pneumonia. Combination therapy over monotherapy remains to be advantageous due to synergism and decreased resistance development. The choice of the second drug to be used should be based on full susceptibility, or if unavailable, a drug with the least minimum inhibitory concentration relative to the breakpoint set by the Clinical and Laboratory Standards Institute. Using the mnemonic ESCAPE can also guide physicians in their polymyxin prescription process: (1) Checking if the pathogen is Extensively resistant or multi-drug resistant; (2) checking the patient’s clinical status if compatible with Significant infection; (3) using Combination therapy; (4) ensuring Adequate dosing; (5) Proper preparation and administration of drug; and (6) keeping an Eye for response and adverse effects.
Polymyxin B ; Colistin ; Polymyxins