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In the last years the rapid expansion of multidrug-resistant A. baumannii strains have become a major health problem. Efflux pumps are a group of transport proteins that contribute to the development of antibiotic resistance. The aim of this study was to evaluate the effect of the efflux pump inhibitor carbonyl cyanide 3-chlorophenylhydrazone (CCCP) on the antimicrobial action of imipenem and cefepime on clinical strains of A. baumannii. A total of 49 non-duplicate clinical samples were collected during January through December of 2018 from patients hospitalized in the Hospital Regional Docente de Cajamarca. Of the 49 samples obtained, the confirmatory identification of A. baumannii was performed on 47 samples by molecular methods. The amplification of the blaOXA-51-like gene was carried out by polymerase chain reaction (PCR). The determination of the minimum inhibitory concentration (MIC) was calculated using the microdilution method in culture broth. The susceptibility to both antibiotics (cefepime and imipenem) was evaluated in the presence and absence of the inhibitor carbonyl cyanide 3-chlorophenylhydrazone (CCCP). A total of 47 strains of A. baumannii were isolated: 97.87% (46/47) were resistant to Imipenem, 2.13% (1/47) of them were classified as intermediate and none of these strains were susceptible. On the other hand, 51.06% (24/47) of isolates were resistant to cefepime; 19.15% (9/47) intermediate and 29.79% (14/47) susceptible. We considered a significant difference in antibiotic susceptibility if the MIC changed at least 4 dilutions, after the addition of the inhibitor. In the case of CCCP in addition to imipenem, 2.1% (1/47) had a significant change of 4 or more reductions in MIC, 59.6% (28/47) achieved a change equal or less than 3 dilutions and 17.0% (8/47) did not have any change. In the case of CCCP with cefepime the percentage of strains with the significant change of MIC was 8.5% (4/47). On the other hand, 53.2% (24/47) presented a reduction equal or less than 3 dilutions and 12.8% (6/47) did not show changes. In conclusion, our results demonstrate that the use of CCCP may improve the antibiotic effect of imipenem and cefepime on clinical strains of A. baumannii. The relevance of this study is that it provides evidence that this efflux pump inhibitor may be an alternative treatment against multidrug-resistant A. baumannii.

Oropouche fever is an infectious disease caused by the Oropouche virus (OROV). The diagnosis and prediction of the clinical picture continue to be a great challenge for clinicians who manage patients with acute febrile syndrome. Several symptoms have been associated with OROV virus infection in patients with febrile syndrome; however, to date, there is no clinical prediction rule, which is a fundamental tool to help the approach of this infectious disease. To assess the performance of a prediction model based solely on signs and symptoms to diagnose Oropouche virus infection in patients with acute febrile syndrome. Validation study, which included 923 patients with acute febrile syndrome registered in the Epidemiological Surveillance database of three arbovirus endemic areas in Peru. A total of 97 patients (19%) were positive for OROV infection in the development group and 23.6% in the validation group. The area under the curve was 0.65 and the sensitivity, specificity, PPV, NPV, LR + and LR- were 78.2%, 35.1%, 27.6%, 83.6%, 1.20 and 0.62, respectively. The development of a clinical prediction model for the diagnosis of Oropouche based solely on signs and symptoms does not work well. This may be due to the fact that the symptoms are nonspecific and related to other arbovirus infections, which confuse and make it difficult to predict the diagnosis, especially in endemic areas of co-infection of these diseases. For this reason, epidemiological surveillance of OROV in various settings using laboratory tests such as PCR is important.

Human rhinovirus is a major cause of acute respiratory infections (ARIs) worldwide. Epidemiological data on human rhinovirus (RV) in Peru is still scarce, as well as its role in respiratory infections in children. Therefore, the aim of this study was to describe the prevalence of rhinovirus and to identify the circulating species in nasopharyngeal swabs from children with acute respiratory infections. We analyzed nasopharyngeal swab samples that were collected from children younger than 17 years old, who had a clinical diagnosis of ARI from the \"Hospital Nacional Cayetano Heredia\" between May 2009 and December 2010. The original study recruited 767 inpatients with ARI, 559 samples of which were included and analyzed in the current study. Detection of rhinovirus and determination of rhinovirus species were characterized by PCR. Rhinovirus was detected in 42.22% samples (236/559), RV-A was detected in 10.17% (24/236) of the cases, RV-B in 16.53% (39/236), and RV-C in 73.31% (173/236). The age group with the highest number of cases was the 0-5 months group with 45.97%, followed by the 1-5 years group with 25.22%. Most of the positive RV cases, i.e., 86.44% (204/236), were hospitalized. The most common signs and symptoms found in patients who tested positive for RV were cough (72.88%), fever (68.64%), rhinorrhea (68.22%), and respiratory distress (61.44%). Infection with RV-A was associated with wheezing (p = 0.02). Furthermore, RV-C was related to cough (p = 0.01), wheezing (p = 0.002), and conjunctival injection (p = 0.03). A peak in RV-C cases was found in March (32 cases in 2010); June (18 cases in 2009 and 12 cases in 2010), which corresponds to the fall season in Peru; and also November (17 cases in 2009 and 4 cases in 2010), which corresponds to spring. RV-A and RV-B cases were constant throughout the year. In conclusion, we found a high prevalence of rhinovirus C infection among pediatric patients with acute respiratory infections in Lima, Peru. This viral infection was more common in children between 0 to 5 months old, and was associated with cough, wheezing, and conjunctival injection. Epidemiological surveillance of this virus should be strengthened/encouraged in Peru to determine its real impact on respiratory infections.

Background Klebsiella pneumoniae is a World Health Organization priority pathogen because of its rapidly accumulating resistance to multiple drug classes. Over-expression of the AcrAB and OqxAB Resistance-Nodulation-Division (RND) efflux pumps is a key mechanism, yet genomic data on these systems in Peruvian strains are scarce. Methods Sixteen non-duplicate K. pneumoniae isolates obtained from hospitalised patients in Lima (2019–2020) were tested for ciprofloxacin and amikacin susceptibility by broth microdilution, with and without the efflux-pump inhibitors carbonyl cyanide m-chlorophenylhydrazone (CCCP) and phenylalanine-arginine β-naphthylamide (PAβN). AcrA, AcrB, OqxA and OqxB were detected by PCR, and the resulting amplicons were sequenced on the Oxford Nanopore platform. Reads were analysed with Epi2me (Amplicon workflow); single nucleotide polymorphisms (SNPs) were identified by aligning to reference sequences in MEGA, and all sequences were deposited in GenBank. Results Resistance to ciprofloxacin and amikacin was evaluated in all isolates; 93.8% were resistant to ciprofloxacin and 18.8% to amikacin. PAβN produced a ≥ 4-fold MIC reduction in 18.8% (ciprofloxacin) and 100% (amikacin) of resistant strains; CCCP yielded a ≥ 3-fold decrease in 75% of ciprofloxacin resistant isolates. AcrB and AcrA were detected in 56.3% and 43.8% of isolates, while OqxB and OqxA occurred in 25.0% and 31.3%, respectively. Nanopore sequencing con-firmed gene identity and revealed 12 SNPs detected, OqxB c.56 G > T (V19F) and c.356 C > A (P119H), which may modulate efflux efficiency. Conclusion Efflux-mediated resistance to ciprofloxacin and amikacin in clinical isolates of K. pneumoniae is underpinned by genetic variants in the AcrAB and OqxAB pumps. The incorporation of long-read amplicon sequencing exposes SNP-level variation missed by conventional PCR studies and underscores the value of routine genomic surveillance. The MIC reversals observed with PAβN and CCCP against these two antibiotics highlight efflux pump inhibition as a promising complementary strategy against resistant K. pneumoniae.

Background. Severe periodontal disease is highly prevalent worldwide, affecting 20% of the population between the ages of 35 and 44 years. The etiological epidemiology in Peru is scarce, even though some studies describe a prevalence of 48.5% of periodontal disease in the general population. Periodontitis is one of the most prevalent oral diseases associated with site-specific changes in the oral microbiota and it has been associated with a socioeconomic state. This study aimed to determine the etiology and resistance profile of bacteria identified in a group of Peruvian patients with periodontal disease. Methods. Six subgingival plaque samples were collected from eight patients with severe periodontitis. Bacterial identification was carried out by an initial culture, PCR amplification, and subsequently DNA sequencing. We evaluated the antibiotic susceptibility by the disk diffusion method. Results. Variable diversity in oral microbiota was identified in each one of the eight patients. The bacterial genus most frequently found was Streptococcus spp. (15/48, 31.3%) followed by Rothia spp. (11/48, 22.9%), Actinomyces spp. (9/48, 18.8%), and Eikenella spp. (4/48, 8.3%). The most common species found was Rothia dentocariosa (8/48, 16.7%). The antimicrobial susceptibility assay varied according to the species tested; however, among all the isolates evaluated, Actinomyces naeslundii was resistant to penicillin and tetracycline; Eikenella corrodens was resistant to dicloxacillin; and Rothia dentocariosa was resistant to amoxicillin + clavulanic acid and metronidazole but also susceptible to trimethoprim-sulfamethoxazole. Conclusions. The most prevalent periodontal bacterium found in this study was Rothia dentocariosa. Specific antimicrobial therapy is required to improve the treatment outcomes of patients with periodontal disease and avoid antibiotic resistance.

Background Arboviruses such as Dengue virus (DENV), Chikungunya virus (CHIKV), Zika virus (ZIKV), and Mayaro virus (MAYV) are major causes of acute febrile illness (AFI) in Peru. However, their overlapping clinical symptoms complicate differential diagnosis. Identifying immunological markers like cytokine profiles could facilitate differential diagnosis and improve understanding of their immunopathogenesis. This study aimed to describe the cytokine responses (IL-2, IL-6, IL-10, TNF-α, IFN-γ) associated with each infection. Methods A cross-sectional study was conducted from June 2020 to April 2022 in Cajamarca, Peru, including 20 patients each with DENV, CHIKV, ZIKV, or MAYV infection, and 20 healthy controls. Infections were confirmed by RT-PCR and virus-specific IgM ELISAs. Serum cytokine levels (IL-2, IL-6, IL-10, TNF-α, IFN-γ) were measured by ELISA. Cytokine profiles were compared across the four infections and controls, and cytokine kinetics were analyzed by stratifying patients by days post-symptom onset. Results All four infections presented with overlapping acute symptoms (e.g., fever, headache, myalgia, arthralgia). Despite these clinical similarities, each infection presented a different cytokine profile. IL-2 levels were comparable among the arbovirus groups (though higher in DENV and patients with ZIKV infection than in controls). IL-6 was elevated predominantly in CHIKV and ZIKV; IL-10 was highest in DENV; and TNF-α and IFN-γ were significantly elevated in DENV and ZIKV (with DENV levels exceeding those in MAYV). Analysis of cytokine dynamics showed that levels of all five cytokines generally peaked early (days 1–4 post-symptom onset) and declined thereafter, with the timing and magnitude of peak responses varying by virus. Conclusion Each arboviral infection analyzed presented a distinct cytokine profile, with elevated IL-6 levels in CHIKV and ZIKV. IL-2, IL-10, TNF-α, and IFN-γ levels were elevated among the flaviviruses studied, with a delayed increase in IL-2 observed in ZIKV patients. Clinical trial number Not applicable.

Arboviral diseases are one of the most common causes of acute febrile illness (AFI) and a significant health problem in South America. In Peru, laboratory etiologic identification of these infections occurs in less than 50% of cases, leading to underdiagnoses of important emerging arboviruses. To assess the prevalence of the Dengue (DENV), Oropouche (OROV), Chikungunya (CHIKV), Mayaro (MAYV) and Zika (ZIKV) viruses in patients with acute febrile illness from Puerto Maldonado (Peru). Serum samples were obtained from patients with AFI during January 2016 to March 2016. A total of 139 specimens were analyzed for the presence of DENV, OROV, CHIKV, MAYV, and ZIKV using polymerase chain reaction (PCR). CHIKV in 9.4% and OROV in 8.6% were the most prevalent arboviruses, followed by DENV and ZIKV, with a prevalence of 6.5% and 5%, respectively. Among all patients, the most common symptoms accompanying fever were headaches 79.9%, muscle pain 65.5% and joint pain 63.3%. During this short 3-month period, 4 arboviruses were detected by PCR, CHIKV and OROV being the most common arboviruses in Puerto Maldonado (Peru). Thus, it is crucial to include OROV detection in the national health surveillance. Furthermore, the etiologic clinical diagnosis of arboviral infections is not possible due to the low specificity of symptoms; therefore an increase of cases confirmed by molecular diagnostic methods will enhance arboviral surveillance in Peru.

The Chikungunya virus (CHIKV) is an emerging arthropod-borne virus (arbovirus) that causes undifferentiated acute febrile illness. Cases of CHIKV may be under-reported in Peru, given the various difficulties in diagnosing it, such as lack of diagnostic tests in remote areas, the passive nature of epidemiological surveillance, and co-circulation of other arthropod-borne pathogens. Therefore, a study was conducted in the high jungle of northern Peru to determine the prevalence of CHIKV among febrile patients and describe their clinical characteristics. A cross-sectional study was conducted in the province of Jaen, Cajamarca, located in the high jungle of northern Peru. Patients attending primary healthcare centers within Cajamarca's Regional Health Directorate were enrolled. The study took place from June 2020 through June 2021. Patients were eligible if they sought outpatient healthcare for a clinical diagnosis of acute febrile illness (AFI). Serum samples were collected from all patients, and the diagnosis of CHIKV was determined using real-time RT-PCR, as well as the detection of IgM antibodies by ELISA. A logistic regression model was employed to identify the risk factors for CHIKV, and the odds ratios (ORs) were calculated, along with their corresponding 95% confidence intervals (95% CI). A total of 1 047 patients with AFI were included during the study period. CHIKV was identified in 130 patients of 1 047 (12.4%). Among the CHIKV positive cases, 84 of 130 (64.6%) were diagnosed by RT-PCR, 42 of 130 (32.3%) by IgM ELISA detection, and 4 of 130 (3.1%) by both assays. The majority of patients with CHIKV infection fell within the 18-39 years age group (50.0%), followed by the 40-59 years age group (23.9%) and those with 60 years or older (10.8%). The most common clinical symptoms observed in patients with CHIKV infection were headache (85.4%), myalgias (72.3%), and arthralgias (64.6%). The highest number of positive CHIKV cases occurred in May (23.1%), followed by March (20.0%) and February (13.8%) of 2021. The study reports a considerable frequency of CHIKV infections among patients with AFI from the high jungle of northern Peru. These findings highlight the importance of recognizing CHIKV as an ongoing pathogen with continuous transmission in various areas of Peru. It is crucial to enhance epidemiological surveillance by implementing reliable diagnostic techniques, as the clinical symptoms of CHIKV infection can be nonspecific.

Background At the end of 2019, a novel coronavirus denominated SARS-CoV-2 rapidly spread through the world causing the pandemic coronavirus disease known as COVID-19. The difference in the inflammatory response against SARS-CoV-2 infection among people living at different altitudes is a variable not yet studied. Methods A descriptive cross-sectional study was performed in two Peruvian cities at different altitudes for comparison: Lima and Huaraz. Five important proinflammatory cytokines were measured including: IL-6, IL-2, IL-10, IFN- γ and TNF-α using ELISA assays. Results A total of 35 COVID-19 patients and 10 healthy subjects were recruited from each study site. The mean levels of IL-6 (p < 0.03) and TNF-α (p < 0.01) were significantly different among the study groups. In the case of IL-6, patients from Lima had a mean level of 16.2 pg/ml (healthy) and 48.3 pg/ml (COVID-19), meanwhile, patients from Huaraz had levels of 67.3 pg/ml (healthy) and 97.9 pg/ml (COVID-19). Regarding TNF-α, patients from Lima had a mean level of 25.9 pg/ml (healthy) and 61.6 pg/ml (COVID-19), meanwhile, patients from Huaraz had levels of 89.0 pg/ml (healthy) and 120.6 pg/ml (COVID-19). The levels of IL-2, IL-10 and IFN-γ were not significantly different in the study groups. Conclusion Patients with COVID-19 residing at high-altitude tend to have higher levels of inflammatory cytokines compared to patients living at sea level, particularly IL-6 and TNF-α. A better understanding of the inflammatory response in different populations can contribute to the implementation of therapeutic and preventive approaches. Further studies evaluating more patients, a greater variety of cytokines and their clinical impact are required.

The rapid expansion of the novel SARS-CoV-2 virus has raised serious public health concerns due to the possibility of misdiagnosis in regions where arboviral diseases are endemic. We performed the first study in northern Peru to describe the detection of SARS-CoV-2 IgM antibodies in febrile patients with a suspected diagnosis of dengue and chikungunya fever. A consecutive cross-sectional study was performed in febrile patients attending primary healthcare centers from April 2020 through March 2021. Patients enrolled underwent serum sample collection for the molecular and serological detection of DENV and CHIKV. Also, serological detection of IgM antibodies against SARS-CoV-2 was performed. 464 patients were included during the study period, of which (40.51%) were positive for one pathogen, meanwhile (6.90%) presented co-infections between 2 or more pathogens. The majority of patients with monoinfections were positive for SARS-CoV-2 IgM with (73.40%), followed by DENV 18.09% and CHIKV (8.51%). The most frequent co-infection was DENV + SARS-CoV-2 with (65.63%), followed by DENV + CHIKV and DENV + CHIKV + SARS-CoV-2, both with (12.50%). The presence of polyarthralgias in hands (43.75%, p<0.01) and feet (31.25%, p = 0.05) were more frequently reported in patients with CHIKV monoinfection. Also, conjunctivitis was more common in patients positive for SARS-CoV-2 IgM (11.45%, p<0.01). The rest of the symptoms were similar among all the study groups. SARS-CoV-2 IgM antibodies were frequently detected in acute sera from febrile patients with a clinical suspicion of arboviral disease. The presence of polyarthralgias in hands and feet may be suggestive of CHIKV infection. These results reaffirm the need to consider SARS-CoV-2 infection as a main differential diagnosis of acute febrile illness in arboviruses endemic areas, as well as to consider co-infections between these pathogens.