Opportunistic infections (OIs) caused by Pseudomonas aeruginosa are clinically relevant complications in immunocompromised oncology patients. This nosocomial pathogen exhibits high antimicrobial resistance and biofilm formation capacity, which compromise the effectiveness of conventional antibiotic therapy.^(1–3)

Cancer patients, especially those undergoing chemotherapy or radiotherapy, often develop oral mucosal lesions due to multiple factors, including immunosuppression, treatment-induced oral mucositis, and OIs such as P. aeruginosa.⁽⁴⁾ These systemic conditions contribute to delayed healing and prolonged symptoms. Patients receiving these treatments are particularly susceptible to OIs because of mucosal damage and immunosuppression.⁽⁴⁾

In this context, adjuvant light-based therapies have emerged as valuable tools for controlling OIs and promoting tissue repair. Antimicrobial photodynamic therapy (aPDT) uses a photosensitizer activated by light to reduce microbial load, whereas photobiomodulation (PBM) stimulates tissue repair, with both therapies potentially acting synergistically in oral infection control.^(5,6) Although the individual efficacy of aPDT and PBM has been demonstrated in several oral conditions, clinical reports describing their combined use for P. aeruginosa infections remain scarce.^(5,7–10) The integration of both modalities may enhance microbial control and accelerate mucosal healing when combined with targeted systemic antibiotics.^(5,6)

Most published reports describe P. aeruginosa infections of the skin rather than the oral cavity. Eduardo et al.⁽¹¹⁾ reported a case of severe oral P. aeruginosa infection refractory to systemic antibiotic therapy, in which complete remission occurred only after 3 weeks of consecutive aPDT sessions. Aspiroz et al.⁽¹²⁾ described the efficacy of photodynamic therapy with methylene blue for P. aeruginosa skin ulcers. Lago et al.^(5,9) demonstrated favorable outcomes with combined aPDT and PBM for herpes simplex lesions, whereas Khalil and Hamadah⁽¹⁰⁾ systematically reviewed the association of both therapies for herpes labialis. Despite growing interest in this combined approach, most available publications focus on oral lesions of viral origin, graft-versus-host disease, or medication-related osteonecrosis of the jaw.^{(7,8,10–14)} Although in vitro studies have demonstrated the efficacy of aPDT against P. aeruginosa biofilms, clinical evidence for the combined use of aPDT and PBM in oral P. aeruginosa infections remains limited.⁽¹³⁾

This case series presents nine oncology patients with culture-confirmed oral lesions caused by P. aeruginosa, treated with alternating sessions of aPDT and PBM combined with systemic antibiotics guided by antibiogram results, highlighting clinical outcomes and the potential of this combined approach for managing multidrug-resistant oral infections.

The objective of this study was to report a case series of oncology patients with oral mucosal lesions caused by P. aeruginosa treated with antimicrobial photodynamic therapy and photobiomodulation, emphasizing therapeutic protocols, clinical progression of oral lesions, and treatment outcomes.

Nine oncology patients (seven females and two males; mean age 45.0±26.3 years) presented oral mucosal lesions clinically suggestive of bacterial infection. All cases were confirmed by microbiological culture as P. aeruginosa. Lesions were located on the gingiva (n=3), palate (n=3), tongue (n=1), and lip (n=2). Five patients presented multiple oral sites, and one patient had bilateral lesions. Most patients were undergoing chemotherapy or radiotherapy at the time of diagnosis and presented clinical signs of mucositis and local pain. Median healing time was 5 days (range, 3-16). Healing time was defined as the interval between the first treatment session and complete re-epithelialization of the oral mucosa, assessed through clinical examination and photographic comparison of lesion progression during treatment. No standardized clinical scale was used for this evaluation. Baseline demographics, lesion sites, and treatment characteristics are summarized in table 1. Antibiotic treatment consisted mainly of meropenem, followed by ciprofloxacin.

Laboratory findings revealed systemic alterations consistent with infection and immunosuppression. Mean leukocyte count was 5,611±10,513/mm³, and platelet counts averaged 49,554±34,655/mm³, reflecting chemotherapy-induced cytopenia. C-reactive protein levels were elevated in nearly all cases (mean, 117mg/L), and lymphocyte counts were reduced, confirming the patients’ immunocompromised status.

Microbiological cultures demonstrated a consistent pattern of multidrug resistance among the P. aeruginosa isolates. The highest resistance rates were observed for fluoroquinolones, particularly ciprofloxacin, and fourth-generation cephalosporins, such as cefepime and ceftazidime. Resistance to β-lactams, including piperacillin-tazobactam, and carbapenems (imipenem and meropenem) was moderate, whereas all isolates remained fully sensitive to aminoglycosides, namely amikacin, gentamicin, and tobramycin. Intermediate susceptibility was observed in fewer than 20% of isolates, primarily for β-lactam combinations. These findings reflect a pattern of broad resistance, particularly to first-line empirical antibiotics.

Blood cultures were performed in eight patients; only two (25%) were positive for P. aeruginosa, indicating that infections were predominantly localized to the oral cavity. Representative clinical images are shown in figures 1 and 2, illustrating the healing progression of gingival necrosis in patients with hematologic malignancies treated with combined aPDT, PBM, and systemic antibiotics.

All patients received systemic antibiotics selected according to antibiogram results in combination with alternating aPDT (methylene blue, 660nm, 4J/point) and PBM (660nm, 2 J/point). Lesions improved after the first few sessions, with complete resolution occurring within 3 to 16 days (median, 5 days). Pain, erythema, and exudate diminished early during treatment. Clinical assessment of pain, erythema, and exudate was performed through direct examination and serial photographic documentation without standardized clinical scales. Treatment was maintained until complete mucosal re-epithelialization was achieved, regardless of pain resolution. If the patient reported no pain but the lesion had not yet fully healed, sessions continued until complete tissue repair was confirmed. No adverse events or recurrence were observed. The combined protocol promoted rapid mucosal repair even in patients with severe thrombocytopenia and persistent leukopenia, suggesting that the therapeutic effect was primarily local and not dependent on systemic immune recovery.

This case series demonstrates that the combination of aPDT and PBM, together with systemic antibiotic therapy, guided by microbiological culture and antibiogram, may represent an effective adjuvant strategy for oral P. aeruginosa infections in immunocompromised oncology patients. To date, this appears to be the first case series reporting the combined use of aPDT and PBM for managing oral P. aeruginosa lesions in cancer patients with microbiological confirmation. Available literature consists mostly of isolated case reports or studies involving infections in other anatomical sites, such as the skin, which are not directly applicable to the oral cavity.^(9,16,17) Although uncommon, these infections are clinically significant because P. aeruginosa exhibits broad antimicrobial resistance.^(1–4)

All oral lesions achieved complete resolution. Although the observed clinical outcomes suggest favorable healing within 3 to 16 days, the absence of a control group precludes definitive conclusions regarding the isolated efficacy of the intervention. Median healing time was 5 days, considerably shorter than that reported in other clinical studies of P. aeruginosa infections, in which recovery often exceeded 15-20 days despite antibiotic therapy, as described by Lei et al. and Aspiroz et al.^(12,13) Furthermore, Eduardo et al. reported a case of oral P. aeruginosa infection refractory to systemic antibiotic therapy in which complete remission occurred only after 3 weeks of consecutive aPDT sessions.⁽¹¹⁾ Compared with those reports, the healing times observed in this study suggest a potential benefit of the combined therapy. Individual clinical factors should also be considered: the patient with the longest healing time (16 days) had an extremely low leukocyte count (170/mm³), indicating severe immunosuppression that likely delayed tissue repair.

The rapid improvement and resolution of lesions in our patients support the synergistic mechanism of this combined therapy. This multimodal approach acts at different levels: systemic antibiotics provide systemic infection control, whereas topical aPDT generates reactive oxygen species following light activation of methylene blue, leading to bacterial cell wall destruction and reduction of local microbial burden. PBM, in turn, modulates inflammatory response, promotes angiogenesis, and accelerates epithelial repair.^(5–8,10) Alternating these modalities may enhance bacterial elimination while simultaneously promoting tissue healing, which is particularly beneficial in patients with hematologic malignancies or chemotherapy-induced cytopenias whose systemic healing capacity is often limited.

Culture results in this series revealed resistance patterns consistent with previous studies showing high resistance to fluoroquinolones and cephalosporins.^(4,5,7,9,11) However, they partially differ from Ahmed et al., who reported high resistance rates to aminoglycosides, particularly gentamicin (65%) and amikacin (32%) among P. aeruginosa isolates from oncology patients. Data regarding fluoroquinolones were more consistent: Ahmed et al. reported 48% resistance to ciprofloxacin compared with 33% in this study, reinforcing the limited therapeutic role of this drug class in severe OIs.⁽⁴⁾ Universal sensitivity to aminoglycosides reinforces the importance of culture-based antibiotic selection rather than empirical regimens.^(11,12,15) The predominance of negative blood cultures suggests that most infections were localized, emphasizing the advantage of local light-based therapy as an adjunct to systemic management.

Despite growing interest in combining aPDT and PBM for oral lesion management, few clinical studies have specifically addressed opportunistic bacterial infections such as those caused by P. aeruginosa. Most available publications focus on lesions of viral origin, graft-versus-host disease, or medication-related osteonecrosis of the jaw.^{(5,6,9–11,16–18)} Although in vitro studies have demonstrated the efficacy of aPDT against P. aeruginosa biofilms, clinical evidence remains limited.⁽¹³⁾ In this context, the present series contributes novel clinical evidence regarding the alternating application of aPDT and PBM in oncology patients with oral P. aeruginosa infection.

In this setting, the role of hospital-based dentists is critical for early diagnosis and monitoring of the clinical course of oral lesions associated with OIs. Microbiological swab sampling of oral lesions, although still underutilized in many services, enables precise pathogen identification and targeted antibiogram analysis, which is particularly important in immunosuppressed patients, in whom clinical presentation may be nonspecific and infection progression rapid and aggressive.⁽³⁾ The low positivity rate of blood cultures observed in this series, despite local culture confirmation of P. aeruginosa, highlights a key limitation of systemic diagnostic methods in localized OIs.

The therapy was well tolerated, with no adverse effects even in patients with severe thrombocytopenia and leukopenia, corroborating previous safety findings for PBM in oncologic settings.^(8,14,16) These results reinforce the potential of light-based therapy as a safe, rapid, and noninvasive adjunctive therapy for managing resistant oral infections, capable of promoting local healing even under unfavorable systemic conditions.

This case series provides relevant contributions to hospital-based clinical practice. One of its main strengths is the use of a clearly defined therapeutic protocol, supporting reproducibility in institutions with similar patient profiles. The study also reinforces the importance of microbiological culture and antibiogram testing for guiding more effective treatment. Nevertheless, some limitations must be considered. The small sample size limits generalizability and precludes robust statistical analyses. In addition, clinical heterogeneity among patients, including different cancer diagnoses and degrees of immunosuppression, may have influenced outcomes such as healing time.

Future prospective randomized controlled clinical trials are needed to validate the efficacy of combined aPDT and PBM as a therapeutic strategy for immunocompromised patients with opportunistic bacterial infections.

Combined antimicrobial photodynamic therapy and photobiomodulation, together with systemic antibiotic therapy, guided by microbiological culture and antibiogram, resulted in rapid and complete healing of oral P. aeruginosa infections in immunocompromised oncology patients. This multimodal light-based approach proved safe, reproducible, and clinically valuable as an adjunct to systemic antibiotics, representing a promising therapeutic alternative for managing multidrug-resistant oral infections in complex oncologic settings. All cases achieved clinical resolution, with healing times comparable to or shorter than those previously reported in the literature. Local swab-based diagnosis and antibiogram testing enabled identification of high resistance rates to fluoroquinolones and cephalosporins, whereas aminoglycosides remained effective. Although the findings are promising, controlled studies are required to validate this approach for opportunistic bacterial infections.