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

Background: Ardisia serrata (Aunasin) is an endemic Philippine plant of the family Primulaceae, with several studiesshowing the genus Ardisia as having potential antibacterial, antiangiogenic, cytotoxic, and antipyretic properties. Objective: This study aims to determine the antibacterial and antibiofilm-forming activity of Ardisia serrata ethanolic and aqueous extracts on Escherichia coli, Methicillin-Sensitive Staphylococcus aureus (MSSA), and Methicillin-Resistant Staphylococcus aureus (MRSA). Methods: This is an experimental study testing the activity against bacterial strains of E. coli, MSSA, and MRSA using ethanolic and aqueous extracts of A. serrata leaves. Microtiter susceptibility and biofilm inhibition assays were done with two-fold dilutions of the extract against the selected strains using spectrophotometry with optical density (OD) at 600 nm and 595 nm, respectively, to quantify bacterial growth and biofilm inhibition. The bacterial susceptibility and biofilm inhibition activity was reported as percent inhibition (PI). Minimum inhibitory concentration (MIC), and minimum biofilm inhibition concentration (MBIC) values were obtained using logarithmic regression of the PI values. Results: A. serrata ethanolic extracts showed weak growth inhibitory activity against MSSA and MRSA with minimum inhibitory concentration (MIC) values of 2.6192 and 3.2988 mg/mL, respectively, but no biofilm inhibition activity was noted, while the aqueous extracts exhibited negligible biofilm inhibition activity against MSSA and MRSA with minimum biofilm inhibition concentration (MBIC) values of 13.5972 and 8964.82 mg/mL, respectively, and with no growth inhibition activity. Both ethanolic and aqueous extracts showed no growth inhibition and biofilm inhibition activities against E. coli. Conclusion Staphylococcus aureus is susceptible to the bioactivity of the leaf extracts of A. serrata and has potential to be used as an antibacterial in the treatment of infectious diseases.
Methicillin-resistant Staphylococcus aureus ; Escherichia coli ; natural product ; biological products

Background: The COVID-19 pandemic continues to afflict nations worldwide. The Philippines is no exception which has recorded more than 3 million cases as of December 2021 with children comprising 12% of total cases. Since the start of the pandemic, the Pediatric Infectious Disease Society of the Philippines (PIDSP) has been collecting data nationwide, through an online pediatric COVID-19 registry (SALVACION registry), to provide a better understanding of COVID-19 in children in the local setting. Methods: This was an ambispective cohort study of pediatric COVID-19 cases in the Philippines reported from March 2020 to December 2021. Data on clinical features, laboratory findings, disease severity, and treatment outcomes were voluntarily reported by physicians across the country. This study was approved by the Department of Health Single Joint Research Ethics Board. Results: As of December 30, 2021, there were 2,127 cases reported in the registry, with a median age of 5 years (interquartile range: 1-13 years) and mostly mild (41.9%) or moderate (24.5%) in severity. The top symptoms reported were fever (57.9%), cough (42.7%), coryza/colds (29.4%), anorexia (25.2%), and difficulty of breathing (23.1%). The most common comorbidities were hematologic-oncologic diseases (7.4%), neurologic diseases (7.0%) and surgical conditions (4.4%), while the most common coinfections were sepsis (6.3%), dengue fever (4.8%) and healthcare-associated pneumonia (2.1%). Significantly higher median CRP, procalcitonin, D-dimer, ferritin, transaminases and lactate dehydrogenase were seen among severe/critical cases compared to non-severe cases. There was a high frequency of antibiotic use (58%). Most cases recovered, although 172 deaths were reported with an 8.6% case fatality rate. The most common comorbidities in those who died were neurologic (15.7%), cardiac (12.8%) and hematologic (11.6%) diseases. Conclusion Children across all age groups are susceptible to COVID-19 and most cases are mild or moderate in severity. Among severe and critical cases, the most common comorbidities were neurologic, hematologic-oncologic and cardiac diseases. Most patients recovered with supportive management.
COVID-19 ; SARS-CoV-2 ; Child ; Registries ; Philippines

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

Background: Using plants as antimicrobials has long been a practice of traditional healers and validating these customs may lead to the discovery and development of useful herbal medicines. Objective: This study aimed to determine the antibacterial activity of guyabano, tsaang gubat, sambong, and ulasimang bato against common pathogens. Methods: Aqueous or alcoholic leaf extracts of the different medicinal plants were prepared. The solid agar dilution method was used to determine the MIC of guyabano, tsaang gubat, sambong, and ulasimang bato against common pathogens including Staphylococcus aureus, Echerichia coli, Streptococcus pneumoniae, Hemophilus influenzae, Pseudomonas aeruginosa, Salmonella typhi, and Shigella flexneri. Results: The alcoholic leaf extract of guyabano showed moderate activity against oxacillin-sensitive S. aureus with an MIC of 5-6.3 mg/mL. However, tsaang gubat did not exhibit any antibacterial activity for drug-resistant enteric organisms (S. typhi, S. flexneri, and E. coli) and S. aureus at a concentration of 25 mg/mL. Even at a concentration of 100mg/mL, ulasimang bato failed to show any antibacterial activity against drug-resistant S. aureus, S. pneumonia, H. influenzae, E. coli, and P. aeruginosa. Sambong alcoholic extract had some antibacterial activity against penicillin-resistant S. pneumoniae with an MIC of 12.5 mg/mL. Conclusions Guyabano alcoholic leaf extract showed moderate antibacterial activity against oxacillin-sensitive S. aureus. Sambong alcoholic extract likewise exhibited inhibitory activity against S. pneumoniae. However, tsaang gubat and ulasimang bato aqueous extracts failed to show significant antibacterial activity for the pathogens tested.
Anti-Bacterial Agents

Background: Amoebiasis is a global health problem affecting poor regions in the world. Few drugs such as metronidazole are available to treat this disease; unfortunately, it is associated with several serious side effects. Tsaang gubat and ampalaya have been used by traditional healers from different cultures to treat dysentery. Objective: The aim of this research was to provide evidence to validate the use of tsaang gubat and ampalaya leaf extracts for dysentery by determining their anti-amoebic activity. Methods: The tsaang gubat and ampalaya leaves were sourced from the University of the Philippines at Los Baños and processed into a lyophilized aqueous extract. Anti-amoebic activity was determined in an in vitro assay using Entamoeba histolytica HK-9 strain against 10 dose levels (18-10,000 μg/mL). The amoeba and leaf extracts were incubated for 24, 48, and 72 hours. The trophozoites were stained with Trypan blue and dispensed into chambers of a Neubauer hemocytometer. The live trophozoites (unstained) were counted under a binocular microscope. The MIC and IC50 were determined. Metronidazole and DMSO served as positive and negative controls, respectively. Results: Tsaang gubat and ampalaya leaves failed to show anti-amoebic activity and even had increased growth of amoeba at all dose levels. The IC50 of tsaang gubat and ampalaya leaf extracts were >500 μg/mL at 24, 48, and 72 hours. Metronidazole was able to eradicate the amoeba parasite at 24 and 72 hours, while exposure to DMSO did not result in inhibition nor death of the parasite. Conclusion Tsaang gubat and ampalaya aqueous leaf extracts did not exhibit any anti-amoeba activity.
Momordica charantia ; Antiparasitic Agents

Infections caused by invasive fungal species continue to rise due to various contributing factors including the changes in the environmental and weather conditions, lifestyle, the occurrence of natural disasters, and the weakened human immune system. Even though synthetic drugs effectively cure fungal diseases, their unwanted side effects, as well as the rapid rise in resistance, have compelled researchers to develop new antifungal agents. Several medicinal plants are folklorically known to have antifungal activities. Among the traditionally used antifungal herbal plants is Senna alata, commonly known as akapulko and ringworm bush. In the current review, phytochemical analysis and numerous non-clinical studies on akapulko have been performed and confirmed its activity against several fungi pathogenic to humans. Anthraquinone compounds seemed to be the major phytochemicals responsible for its antifungal activity. In the Philippines, clinical trials have also confirmed its utility as a topical agent in treating cutaneous fungal infections. Research gaps that need to be addressed include the determination of the exact molecular mechanisms of their fungal killing action.
Phytochemicals

Background: Surgical site infection (SSI) poses a serious threat in Neurosurgery. The mere presence of SSI would warrant a prompt medical and/ or surgical intervention for the outcome is very poor. This study aims to establish whether a pre-operative hospital stay of >7 days & other risk factors predisposes to surgical site infections. Methods: Retrospective, cross-sectional study of all pediatric patients who underwent clean neurosurgical procedures for the first time from January 1, 2011- June 30, 2014, in the Philippine General Hospital. The primary outcome was the development of a surgical site infection within 30 days from spine surgery or 90 days from intracranial surgery. Univariate and multivariate logistic regression analyses were performed to show the association of demographic and clinical factors with the development of SSI. Results: 279 medical charts were available for review. Median age was 1 year(5 days to 18 years old). The overall prevalence rate of SSI was 11.26%. Patients with >7 days pre-operative hospital stay had an incidence rate for SSI of 76.47% compared to 23.53% in patients with <7 days pre-operative hospital stay (OR 1.61, CI 0.68-3.84, p=0.280). Conclusions The incidence of SSI is high compared to other centers. There was no association of preoperative hospital stay with SSI. The association was significant only for the history of nosocomial infection. Early pre-operative clearance and surgery are recommended. Further prospective studies and surveillance are warranted
Surgical Wound Infection ; Cross Infection

Background: Environmental surfaces harbor pathogens that transmit them and there is a need for environmental cleaning and disinfection to prevent the spread of infection. Objective: This study aimed to determine if the use of fluorescent marking (FM) technique in high touch areas can be used as an index of cleanliness and disinfection as determined by aerobic colony count. Methods: This was an experimental study done at the University of the Philippines Philippine General Hospital Neonatal Intensive Care Unit (NICU). A total of 40 surfaces were swabbed for cultures with aerobic colony count (ACC) then adjacent areas are marked with fluorescent gel. After cleaning and disinfection, checking for residual fluorescent markings with congruent environmental culture with an aerobic colony count of the same surface was done. The rate of removal and colony count were then compared to assess the specificity and sensitivity of the fluorescent marking technique as a gauge of cleanliness of high touch surface areas. Any residual fluorescence of the marked areas was considered unclean and an aerobic colony count of < 2.5 – 5CFU/ml 2 were considered an acceptable level of cleanliness. Result: A total of 40 high contact surfaces were sampled from 5 areas were collected. Prior to cleaning, 60% (24) of the surfaces (60%) did not contain microorganisms. After cleaning, the (FM) had 38% and in the ACC 83% were assessed to be clean. The sensitivity of FM is 85.71% and specificity of 42.42%. The positive predictive value (PPV) is 24% with the positive likelihood ratio (positive LR) of 1.49 and the negative predictive value (NPP) is 93.33%. Conclusion The use of Fluorescent Marking technique in high touch areas as an index of cleanliness and disinfection is a good marker for cleanliness and disinfection. Furthermore, it is a simple, rapid, inexpensive and has potential to increase awareness of the environment that can be utilized as an objective parameter to assess cleanliness and disinfection.
Cross Infection

Objective: Leptospirosis in children is one of the most common diagnostic dilemmas, hence this study was performed to determine the clinical profile, outcome and risk factors associated with mortality in patients seen at tertiary government hospitals from January 2008 to December 2012. Methods: A case-control retrospective study was done among admitted patients at UP-PGH, SLH, and RITM. Descriptive statistics and multiple logistic regressions were utilized. Results: Among the 404 leptospirosis cases included in the study, 94% were male, with 43% belonging to 16-18-year-old age group (age range 3 to 18 years old). A higher occurrence was noted during the rainy season and in Manila. Clinical findings include fever, abdominal pain, calf tenderness, vomiting and conjunctival suffusion. Significant correlation was noted in patients with jaundice (p-value 0.014; OR 6.293, CI 1.449-27.335), dyspnea (p-value 0.004; OR 7.880, CI 1.967-31.561) and cardiac abnormality (p-value 0.042; OR 15.343, CI 1.106-212.853). Abnormal laboratory findings include neutrophilia, azotemia, creatinemia, anemia, elevated bilirubin levels and thrombocytopenia. Prolonged prothrombin time was associated with poor outcome (p-value 0.004, OR 23, CI 2.79-189.67). Penicillin was the drug of choice given to 96.8%. 94.6% of cases who had oliguric renal failure were conservatively converted to non-oliguric type. 5.4% underwent peritoneal dialysis and survived. Inotropes were used in 93% of non-survivors. The case fatality rate was 3.5% with the cause of death mostly due to Weil’s disease. The average hospital stay among survivors was 6.8+3.3 days as compared with 1.8+1.9 days in non survivors. Shorter hospital stay (p-value 0.00; OR 3.514, CI 2.115-5.839), as well as inotropic support (p-value 0.035; OR 62.511, CI 1.33-2949.134), were associated with poorer outcome, but these findings can be attributed to late presentation of cases at the hospital for admission. Conclusion A5 year review of patients with leptospirosis showed that jaundice, dyspnea, cardiac abnormality and prolonged prothrombin time were predictive of mortality.
Leptospirosis