Acinetobacter baumannii is a major pathogen in hospital-acquired infections notorious for its strong acquired resistance and complex drug resistance mechanisms. Owing to the lack of effective drugs, the mortality rate of extensively drug-resistant A. baumannii pneumonia can reach as high as 65%. This article analyzes a case where a combination of cefoperazone-sulbactam, polymyxin B, and minocycline with rifampicin successfully treated XDR-AB pulmonary infection. Combination therapy is effective and has a particular clinical value.

UNASSIGNED: Clinically, Carbapenem-resistant Pseudomonas aeruginosa (CRPA) meningitis is extremely difficult to cure and has a high mortality rate. Intrathecal injection of polymyxins B is suggested to be an effective anti-infective means to treat intracranial infection with CRPA. However, due to the potential drug toxicity of polymyxin B in children, this regimen has rarely been reported in pediatrics.
UNASSIGNED: A 5-year-old male patient diagnosed with Epstein-Barr virus-induced hemophagocytic syndrome (HPS) exhibited persistent fever for over a month despite antibacterial and chemotherapy regimens. During hospitalization, the patient presented with unconsciousness, nystagmus, and myasthenia. Cerebrospinal fluid (CSF) analysis indicated elevated leukocyte counts and protein levels. Sputum and blood cultures, as well as metagenomic next-generation sequencing (mNGS) of CSF, identified CRPA. Intravenous and intrathecal polymyxin B administration resulted in temperature normalization and amelioration of consciousness disturbances and nystagmus. Subsequent CSF analysis yielded normal results, while polymyxin B treatment exhibited no nephrotoxicity or neurotoxicity.
UNASSIGNED: Intrathecal injection of polymyxin B in children with meningitis caused by CRPA is an effective treatment without remarkable adverse events.

Polymyxin B was widely used to treat drug-resistant gram-negative bacteria and showed a better antibacterial effect. However, it is associated with some side effects. It should be remembered that polymyxin B may cause hyperpigmentation, albeit rare. This is a case report of a 68-year-old male patient who developed hyperpigmentation following treatment of a chest infection with polymyxin B. He was a known patient with chronic kidney diasease and chronic obstructive pulmonary disease followed up in the intensive care unit due to acute exacerbation of COPD. Later, polymyxin B treatment was started due to the development of pneumonia caused by the multidrug-resistant Acinetobacter baumannii. On the second day of polymyxin B treatment, hyperpigmentation developed in the face and neck region. The fact that the patient had chronic kidney disease possibly facilitated the development of skin hyperpigmentation due to the cumulative effect of polymyxin B. Hyperpigmentation which a rare side effect of polymyxin B may occur in those with underlying kidney disease.

BACKGROUND: With population aging and lifestyle changes, the number of patients with chronic limb-threatening ischemia (CLTI) is increasing, and refractory or recurrent lesions are more common, especially in chronic dialysis patients. In March 2021, a new type of adsorptive cellulose bead column immobilized with dextran sulfate and L-tryptophan for direct hemoperfusion (DHP) was approved by Japan\'s medical insurance system as a treatment for CLTI.
METHODS: We retrospectively analyzed 17 cases of CLTI in dialysis patients treated with DHP using the novel column (Rheocarna) (DHP-R) at our hospital from May 2021 to October 2022. The short-term of efficacy of DHP-R was judged qualitatively by the foot care team every 2 weeks based on the assessment of skin color, warmth, ulcer epithelialization or shrinkage of the ulcer area, and foot pain. The final judgment of efficacy was made after the final DHP-R session.
RESULTS: The median age of patients was 66 years, the median dialysis duration was 10 years, 15 cases (88%) were male, and 15 cases (88%) had diabetes. The median total number of sessions was eight. In comparing the groups in which DHP-R was effective and ineffective, there was no significant difference in any factors including patient background data (i.e., age, diabetes, low-density lipoprotein cholesterol, hemoglobin, dialysis duration, etc.), type of anticoagulants, and presence of episodes of blood pressure drop or circuit clotting during session. Three cases with symptomatic hypotension during the session and two cases with circuit clotting that did not improve with increased heparin dose all resolved immediately after changing the anticoagulant from heparin to nafamostat mesylate (NM).
CONCLUSIONS: Identification of patients\' characteristics in which DHP-R is favorable and some reliable index that allow a rapid decision to continue DHP-R are needed. In addition, validating whether the use of NM as anticoagulant affects the efficacy of DHP-R for CTLI treatment remains a challenge to resolve.

Spinal muscular atrophy (SMA) is a neurodegenerative disease that results in progressive and symmetric muscle weakness and atrophy of the proximal limbs and trunk due to degeneration of spinal alpha-motor neurons. Children are classified into types 1-3, from severe to mild, according to the time of onset and motor ability. Children with type 1 are the most severe, are unable to sit independently, and experience a series of respiratory problems, such as hypoventilation, reduced cough, and sputum congestion. Respiratory failure is easily complicated by respiratory infections and is a major cause of death in children with SMA. Most type 1 children die within 2 years of age. Type 1 children with SMA usually require hospitalization for lower respiratory tract infections and invasive ventilator-assisted ventilation in severe cases. These children are frequently infected with drug-resistant bacteria due to repeated hospitalizations and require long hospital stays requiring invasive ventilation. In this paper, we report a case of nebulization combined with intravenous polymyxin B in a child with spinal muscular atrophy with extensively drug-resistant Acinetobacter baumannii pneumonia, hoping to provide a reference for the treatment of children with extensively drug-resistant Acinetobacter baumannii pneumonia.

Polymyxin B and colistin are considered the last therapeutic option to treat infections caused by highly drug-resistant bacteria. However, their administration may lead to various adverse effects such as nephrotoxicity, neurotoxicity, and allergic reactions. The current case report presents the clinical manifestation of polymyxin B-associated neurotoxicity in a female patient with no chronic illness history. The patient was rescued from under rubble during an earthquake. She was diagnosed with an intra-abdominal infection caused by Acinetobacter baumannii (A. baumannii) After the initiation of the polymyxin B infusion, the patient developed numbness and tingling sensations in her hands, face, and head. On discontinuing polymyxin B and starting colistimethate, the patient\'s symptoms improved. Therefore, healthcare professionals should be aware of the potential risk factors associated with neurotoxicity in patients receiving polymyxin B. On identifying such symptoms treatment should be discontinued promptly to prevent further neurological damage.

A population pharmacokinetic (pop PK) model of polymyxin B was developed using nonlinear mixed-effects (NONMEM) modeling based on free plasma concentrations to determine whether dose adjustment is required in critically ill patients. One thousand pharmacokinetic profiles for virtual patients with a body weight of 70 kg were simulated using Monte Carlo simulation at different dose scenarios, and area under the concentration-time curve of free drug (fAUC) was computed. The probability of target attainment (PTA) at each minimum inhibitory concentration (MIC) was calculated using fAUC/MIC as a pharmacokinetic/pharmacodynamic (PK/PD) index. The final population PK model was a 2-compartment model. PTA showed that 3.5 mg/kg/day regimens of polymyxin B effectively achieved the fAUC/MIC target of 10 (one log10 kill) against Pseudomonas aeruginosa strains with MIC of 1 mg/L or less (PTA,  90.7% or greater), while the dose regimen were ineffective against strains with an MIC of 2 mg/L or greater (PTA, 56.9% or less). For Klebsiella pneumoniae, the fAUC/MIC target of 17.4 (one log10 kill) was achieved in more than 90.4% of cases for MIC of 0.5 mg/L or less with 3 mg/kg/day regimens. However, the PTA decreased dramatically as MICs increased above 1 mg/L (PTA, 56.1% or less). The polymyxin B dosage regimen of 3.5 mg/kg/day and 3 mg/kg/day are sufficient to treat P. aeruginosa infections with an MIC of 1 mg/L or less and K. pneumoniae infections with an MIC of 0.5 mg/L or less, respectively. The current recommended dose (1.5-3 mg/kg/day) of polymyxin B appears inadequate to attain the PK/PD target for therapeutic efficacy against infections caused by P. aeruginosa and K. pneumoniae isolates when MIC is above the values.

Polymyxin B (PMB) and colistin are bactericidal polypeptide antibiotics discovered in 1947 and 1949 for the treatment of gram-negative bacterial infections. Polymyxin was used clinically in the 1950s, but it was gradually replaced by other antibiotics in the 1980s because of its high nephrotoxicity and neurotoxicity. In recent years, the increase of multidrug-resistant negative bacteria has led to the resurgence of polymyxin use. However, its side effects are not clear. Respiratory paralysis caused by PMB-related neuromuscular blockade is a rare but potentially fatal effect. We report a case of respiratory paralysis probably caused by polymyxin B infusion.

BACKGROUND: The mortality of extensively drug-resistant Gram-negative (XDR GN) bacilli-induced ventilator-associated pneumonia (VAP) is extremely high. The purpose of this study was to compare the efficacy and safety of inhaled (IH) plus intravenous (IV) polymyxin B versus IV polymyxin B in XDR GN bacilli VAP patients.
METHODS: A retrospective multi-center observational cohort study was performed at eight ICUs between January 1st 2018, and January 1st 2020 in China. Data from all patients treated with polymyxin B for a microbiologically confirmed VAP were analyzed. The primary endpoint was the clinical cure of VAP. The favorable clinical outcome, microbiological outcome, VAP-related mortality and all-cause mortality during hospitalization, and side effects related with polymyxin B were secondary endpoints. Favorable clinical outcome included clinical cure or clinical improvement.
RESULTS: 151 patients and 46 patients were treated with IV polymyxin B and IH plus IV polymyxin B, respectively. XDR Klebsiella pneumoniae was the main isolated pathogen (n = 83, 42.1%). After matching on age (± 5 years), gender, septic shock, and Apache II score (± 4 points) when polymyxin B was started, 132 patients were included. 44 patients received simultaneous IH plus IV polymyxin B and 88 patients received IV polymyxin B. The rates of clinical cure (43.2% vs 27.3%, p = 0.066), bacterial eradication (36.4% vs 23.9%, p = 0.132) as well as VAP-related mortality (27.3% vs 34.1%, p = 0.428), all-cause mortality (34.1% vs 42.0%, p = 0.378) did not show any significant difference between the two groups. However, IH plus IV polymyxin B therapy was associated with improved favorable clinical outcome (77.3% vs 58.0%, p = 0.029). Patients in the different subgroups (admitted with medical etiology, infected with XDR K. pneumoniae, without bacteremia, with immunosuppressive status) were with odd ratios (ORs) in favor of the combined therapy. No patient required polymyxin B discontinuation due to adverse events. Additional use of IH polymyxin B (aOR 2.63, 95% CI 1.06, 6.66, p = 0.037) was an independent factor associated with favorable clinical outcome.
CONCLUSIONS: The addition of low-dose IH polymyxin B to low-dose IV polymyxin B did not provide efficient clinical cure and bacterial eradication in VAP caused by XDR GN bacilli. Keypoints Additional use of IH polymyxin B was the sole independent risk factor of favorable clinical outcome. Patients in the different subgroups were with HRs substantially favoring additional use of IH polymyxin B. No patients required polymyxin B discontinuation due to adverse events.

To evaluate the use of direct hemoperfusion with polymyxin B-immobilized fiber (PMX-DHP) as adjunctive therapy during pediatric patients with septic shock.
Prospective observational study.
Nine-bed PICUs at university referral hospital.
Children (30 d to 15 yr) with septic shock and Pediatric Logistic Organ Dysfunction (PELOD)-2 score greater than or equal to 10 or Pediatric Risk of Mortality (PRISM) 3 score greater than or equal to 15, who were also receiving at least one inotrope.
Patients received 2-4 hour treatment with PMX-DHP 20R column on 2 consecutive days.
We enrolled six children aged 21-167 months old (median, 99-mo old), with a body weight of 10-50 kg (median, 28 kg). All six patients had both PELOD-2 greater than or equal to 10 and PRISM-3 greater than or equal to 15, required invasive mechanical ventilation, and received standard treatment for septic shock before enrollment. We observed significant improvement in PELOD-2 score from baseline to 72 hours after the start of PMX-DHP (mean [95% CI] from 14.3 [12.2-16.5] to 6.0 [0.3-11.7]; p = 0.006). The vasoactive inotropic score (VIS) and lactate concentration also significantly decreased from baseline to 72 hours (VIS, 60 mmol/L [25-95 mmol/L] to 4.0 mmol/L [44.1-12 mmol/L]; p = 0.003; lactate, 2.4 mmol/L [1.0-3.8 mmol/L] to 1.0 mmol/L [0.5-1.5 mmol/L]; p = 0.01). Five of six patients survived. There was no device-related adverse event in these patients.
In this case series of treatment with PMX-DHP as adjunctive therapy in children with refractory septic shock and high baseline severity, we have shown that patient recruitment is feasible. We have also found that clinical hemodynamic and severity of illness scores at 72 hours may be potential end points for testing in future randomized controlled trials.