Polymyxin B‐induced skin hyperpigmentation

Li, Yumeng M.; Milikowski, Clara; Selvaggi, Gennaro; Abbo, Lillian M.; Skiada, Dimitra; Galimberti, Fabrizio

doi:10.1111/tid.13312

Cited by 16 publications

(17 citation statements)

References 19 publications

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“…Experimental trials for the scavenging of reactive species and halting apoptosis in cell lines using certain agents claimed to be neuroprotective, such as minocycline and rapamycin, are underway [ 59 , 61 , 62 ]. Finally, apart from the above adverse effects and in some reports, skin hyperpigmentation was documented with intravenous polymyxin B, and was associated with melanocyte activation and inflammatory process in the skin [ 63 , 64 ].…”

Section: Clinically Useful Polymyxins and Their Principle Propertimentioning

confidence: 99%

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Polymyxins and Bacterial Membranes: A Review of Antibacterial Activity and Mechanisms of Resistance

2020

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Following their initial discovery in the 1940s, polymyxin antibiotics fell into disfavor due to their potential clinical toxicity, especially nephrotoxicity. However, the dry antibiotic development pipeline, together with the rising global prevalence of infections caused by multidrug-resistant (MDR) Gram-negative bacteria have both rejuvenated clinical interest in these polypeptide antibiotics. Parallel to the revival of their use, investigations into the mechanisms of action and resistance to polymyxins have intensified. With an initial known effect on biological membranes, research has uncovered the detailed molecular and chemical interactions that polymyxins have with Gram-negative outer membranes and lipopolysaccharide structure. In addition, genetic and epidemiological studies have revealed the basis of resistance to these agents. Nowadays, resistance to polymyxins in MDR Gram-negative pathogens is well elucidated, with chromosomal as well as plasmid-encoded, transferrable pathways. The aims of the current review are to highlight the important chemical, microbiological, and pharmacological properties of polymyxins, to discuss their mechanistic effects on bacterial membranes, and to revise the current knowledge about Gram-negative acquired resistance to these agents. Finally, recent research, directed towards new perspectives for improving these old agents utilized in the 21st century, to combat drug-resistant pathogens, is summarized.

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Section: Clinically Useful Polymyxins and Their Principle Propertimentioning

confidence: 99%

“…In E. coli , and parallel to the mgrB mechanism, mgrR is a key genetic determinant of polymyxin resistance in this organism [ 63 ]. The mgrR mediates the modification of the outer Kdo (3-deoxy-D-manno-octulosonic acid) residues of LPS by adding pEtN [ 152 ].…”

Section: Special Features and Spread Of Polymyxin Resistance Amongmentioning

confidence: 99%

Polymyxins and Bacterial Membranes: A Review of Antibacterial Activity and Mechanisms of Resistance

2020

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“…Histological and immunohistochemical results of pigmented skin in patients with polymyxin B treatment showed an abundant melanocyte-pigmented dendritic network. Langerhans cells' hyperplasia and dermal IL-6 overexpression were also found, presumably for an inflammatory process due to polymyxin B use (Mattos et al, 2016;Li et al, 2020;Wen et al, 2020); At the same time, although hyperpigmented skin did not show signs of inflammationby clinical inspection, under microscopic view the dermis contained mild-to-moderate perivascular inflammatory infiltrate of lymphocytes and histiocytes. Langerhans cells are antigen-presenting cells, which play an important role in skin immunity and inflammation.…”

Section: The Skin Inflammation Process Is Related To the Activation Of Melanocytesmentioning

confidence: 92%

The Difference Between Polymyxin B and Polymyxin E in Causing Skin Hyerpigmentation

Zou

2021

Front. Pharmacol.

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“…Many drugs are associated with skin hyperpigmentation such as nonsteroidal anti-inflammatory agents, antihypertensive agents, antibiotics, and psychoactive agents ( Giménez García and Carrasco Molina, 2018 ). Nephrotoxicity and neurotoxicity are common adverse reactions of polymyxin B, while skin hyperpigmentation was also reported as a side effect recently ( Li et al., 2020 ). Reports of polymyxin B associated skin hyperpigmentation in adults were rare, unlike in neonates ( Zavascki et al., 2015 ; Gothwal et al., 2016 ).…”

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confidence: 99%

“…Polymyxin B is mainly excreted through the kidney, dosage adjustment is required in patients with lower creatinine clearance ( Zheng et al., 2018 ). The cumulation of polymyxin B might be a possible reason for skin hyperpigmentation in neonates due to their immature kidney function ( Gothwal et al., 2016 ; Li et al., 2020 ).…”

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confidence: 99%

Skin Hyperpigmentation in Coronavirus Disease 2019 Patients: Is Polymyxin B the Culprit?

Hou

2020

Front. Pharmacol.

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From mid-December 2019, the outbreak of the coronavirus disease 2019 (COVID-19) in Wuhan has spread worldwide and become an emergency of major international concerns (Pascarella et al., 2020). Recently, a television report has drawn extensive attention of the public in China. Two frontline doctors of the central hospital of Wuhan, Fan Yi and Weifeng Hu, were unfortunately infected by COVID-19. Cutaneous hyperpigmentation of the two doctors was noticed in the TV interview. Many people expressed grave concerns about the pathogenesis and prognosis of their skin pigmentary disorder. Fan Yi and Weifeng Hu were diagnosed with COVID-19 infection on January 18 and January 28, respectively. The illness progress of the two doctors was very rapid and they were transferred to the intensive care unit for further treatment. Extracorporeal membrane oxygenation (ECMO) was provided as rescue therapy for respiratory failure. Because of prolonged hospital stay, mechanical ventilation, and presence of invasive devices, some critically ill patients suffered from infections caused by multidrug-resistant (MDR) bacteria (Bassetti et al., 2018). Polymyxin B was used in these two doctors for the treatment of MDR infections. Polymyxin B is a cyclic polypeptide antibiotic that regained significant interest due to the inevitable appearance of MDR bacteria (Rigatto et al., 2019). It is even being considered as last resort therapy against some intractable gram-negative bacteria (Manchandani et al., 2018). Acquired skin hyperpigmentation is a common dermatologic complaint, which is attributable to drugs up to 20% of all cases (Nahhas et al., 2019). Many drugs are associated with skin hyperpigmentation such as nonsteroidal anti-inflammatory agents, antihypertensive agents, antibiotics, and psychoactive agents (Gimeńez Garcıá and Carrasco Molina, 2018). Nephrotoxicity and neurotoxicity are common adverse reactions of polymyxin B, while skin hyperpigmentation was also reported as a side effect recently (Li et al., 2020). Reports of polymyxin B associated skin hyperpigmentation in adults were rare, unlike in neonates (Zavascki et al., 2015; Gothwal et al., 2016). Polymyxin B is mainly excreted through the kidney, dosage adjustment is required in patients with lower creatinine clearance (Zheng et al., 2018). The cumulation of polymyxin B might be a possible reason for skin hyperpigmentation in neonates due to their immature kidney function (Gothwal et al., 2016; Li et al., 2020). Kidney involvement is prevalent in patients with COVID-19. Acute kidney injury (AKI) has been reported in approximately 20%-40% of critically ill or deceased COVID-19 patients (Ronco et al., 2020). Several mechanisms are possibly involved in COVID-19 associated AKI, including direct damage action of the virus, hemodynamic alterations, inflammatory cytokines, administration of nephrotoxic drugs, and mechanical ventilation (Gabarre et al., 2020; Martinez-Rojas et al., 2020). According to these findings, we speculate that AKI may be an important factor

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Polymyxin B‐induced skin hyperpigmentation

Cited by 16 publications

References 19 publications

Polymyxins and Bacterial Membranes: A Review of Antibacterial Activity and Mechanisms of Resistance

Polymyxins and Bacterial Membranes: A Review of Antibacterial Activity and Mechanisms of Resistance

The Difference Between Polymyxin B and Polymyxin E in Causing Skin Hyerpigmentation

Skin Hyperpigmentation in Coronavirus Disease 2019 Patients: Is Polymyxin B the Culprit?

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