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Introduction: For pregnant women, vaccination with inactivated influenza vaccine (IIV) and tetanus, diphtheria, acellular pertussis vaccine (Tdap) is recommended. In Peru, uptake is nonetheless low. A study was conducted to identify factors affecting maternal vaccination coverage. The study's primary objectives were to describe the knowledge, attitudes, and practices regarding maternal immunization among pregnant/postpartum women and health care professionals (HCPs). The secondary objective was to determine the vaccination coverage and the impact of Ministry of Health (MOH) recommendations. Methods: An observational multicenter, cross-sectional survey study was conducted from February 1, 2021 to June 30, 2021 in five cities in Peru. Two surveys were conducted to assess knowledge, attitudes, and practices concerning maternal immunization: one among pregnant/postpartum women and one among HCPs. Results: Participants were 668 pregnant/postpartum women with a mean age of 29.6 years and 219 HCPs—mostly midwives (46.6%) and obstetricians/gynecologists (44.7%). Of the pregnant/postpartum women, 66.9% knew that, in general, vaccinations are given for prevention, and 98.5% believed vaccines are important. Nonetheless, 69.6% of pregnant/postpartum women had poor or moderate knowledge of maternal vaccination. Disease knowledge of influenza (89.1%) and tetanus (87.0%) was high, while knowledge of pertussis (37.7%) was low. Women agreed/strongly agreed that they would get vaccinated with Tdap if a doctor (96.3%), midwife (88.9%), or nurse (72.0%) recommended it. Of the HCPs, 81.3% routinely recommended Tdap vaccination for pregnant women. Conclusions: To enhance vaccine acceptance in pregnant women in Peru, we must improve knowledge of the diseases, MOH recommendations, and benefits of the offered vaccinations. HCPs could provide this vaccination knowledge and information along with their vaccination recommendation as the pregnant/postpartum women indicated they would take the vaccines if recommended by their HCPs. Our findings are important for the successful implementation of maternal immunization programs in Peru. Plain Language Summary: [ABSTRACT FROM AUTHOR]

Streptococcus pneumoniae upper respiratory infections and pneumonia are often treated with macrolides, but recently macrolide resistance is becoming an increasingly important problem. The 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in the National Immunization Program of Peru in 2015. This study aimed to evaluate the temporal evolution of macrolide resistance in S. pneumoniae isolates collected in five cross-sectional studies conducted before and after this vaccine introduction, from 2006 to 2019 in Lima, Peru. A total of 521 and 242 S. pneumoniae isolates recovered from nasopharyngeal swabs from healthy carrier children < 2 years old (2 carriage studies) and samples from normally sterile body areas from pediatric patients with invasive pneumococcal disease (IPD) (3 IPD studies), respectively, were included in this study. Phenotypic macrolide resistance was detected using the Kirby-Bauer method and/or MIC test. We found a significant increase in macrolide resistance over time, from 33.5% to 50.0% in carriage studies, and from 24.8% to 37.5% and 70.8% in IPD studies. Macrolide resistance genes [ erm (B) and mef (A/E)] were screened using PCR. In carriage studies, we detected a significant decrease in the frequency of mef (A/E) genes among macrolide-resistant S. pneumoniae strains (from 66.7% to 50.0%) after introduction of PCV13. The most common mechanism of macrolide-resistant among IPD strains was the presence of erm (B) (96.0%, 95.2% and 85.1% in the 3 IPD studies respectively). Macrolide resistance was more common in serotype 19A strains (80% and 90% among carriage and IPD strains, respectively) vs. non-serotype 19A (35.5% and 34.4% among carriage and IPD strains, respectively). In conclusion, S. pneumoniae macrolide resistance rates are very high among Peruvian children. Future studies are needed in order to evaluate macrolide resistance trends among pneumococcal strains, especially now after the COVID-19 pandemic, since azithromycin was vastly used as empiric treatment of COVID-19 in Peru. [ABSTRACT FROM AUTHOR]

Background: The inappropriate use of antibiotics significantly contributes to the development of antibiotic resistance. There is limited information about the use of antibiotics among parents from rural areas in Peru. This study aimed to describe the knowledge, attitudes and practices towards antibiotics among parents of children < 5 years of age from rural communities in Peru; to explore the association between knowledge and attitudes towards antibiotics and to explore determinants of low knowledge and self-medicating his/her child with antibiotics.Methods: Cross-sectional study in six rural primary health centres in Peru using a self-administered survey. Crude and adjusted Prevalence Ratios (PR), and 95% Confidence Intervals (95% CI) were calculated to explore determinants of low knowledge and of having self-medicated his/her child with antibiotics. Linear regression was used to explore the association between knowledge and attitudes.Results: A total of 231 parents were included. The largest gap in knowledge was among 183 parents (79%) who did not know that antibiotics cannot cure viral infections. The largest gap in attitudes was among 185 participants (80%) that did not disagree with "If I want my child to receive antibiotics, I would not be satisfied if the doctor refuses to prescribe them". More than half of parents (n = 120, 52%) reported having self-medicated his/her child with antibiotics. A positive correlation was found between knowledge and attitudes (Coefficient 0.53, 95% CI 0.38-0.68) after adjusting for the age and the education of the parent. Parents who were < 20 years old were more likely to have low knowledge about antibiotics (crude PR 2.39, 95% CI 1.32-4.34) compared to those aged > 40 years. Parents who had self-medicated his/her child with antibiotics (n = 120, 52%) were more likely to have purchased antibiotics without prescription (aPR 2.70, 95% CI 1.74-4.19) and to have received antibiotics after the recommendation of a pharmacist (aPR 1.79, 95% CI 1.13-2.82).Conclusions: Knowledge about antibiotics among parents from rural settings in Peru is limited and highlights the need for educational interventions. Public health policies to limit the acquisition of antibiotics without prescription should be implemented. [ABSTRACT FROM AUTHOR]

Background : Antibiotic-resistant Escherichia coli can colonize the intestinal tract of healthy children, causing concern when antibiotic resistance is related to the presence of transferable mechanisms, such as extended-spectrum 13-lactamases (ESBLs). Materials and Methods: Fecal samples from 41 healthy children from two villages of rural Peru were cultured on ceftriaxone-disks. ESBL production was confirmed with double disk synergy. In all ESBL-produced isolates, antibiotic susceptibility to 12 antibacterial agents was established by disk diffusion, while clonal relationships were determined by repetitive extragenic palindromic-polymerase chain reaction (REP-PCR). Presence of ST131 was determined using PCR. Results:Ceftriaxone-resistant microorganisms were recovered from 39 samples belonging to 22 out of41 children (53.7°/o). Of these, 80 ceftriaxone-resistant and two ceftriaxoneintermediate E. coli from inside ceftriaxone-halos were confirmed as ESBL-producers. All isolates were multidrug-resistant. In 79/80 (98.8%) ceftriaxone-resistant isolates, the presence of blacrx-M was detected alone (58 isolates, or together with other D-lactamase (blarEM 17 isolates; blaoxA-1-like, 3 isolates; blarEM + blao>

Introduction: Rotavirus (RV) infection is the leading cause of severe diarrhea in children worldwide. It is responsible for around 25% of gastroenteritis (GE) cases, 33% of hospitalized GE cases, and an annual mortality rate of 113.4/100,000 in children < 5 years of age in Peru. RV infant vaccination is recommended by the World Health Organization and provides the best public health strategy to manage the disease. Universal RV vaccination was introduced in Peru in 2009. Methods: Trends in GE ambulatory visits, hospitalizations, and deaths in children < 5 years of age are described in the pre-vaccination (2004–2008) versus post-vaccination (2010–2018) periods. Time-trend analysis was performed (using generalized linear regression models) to assess the impact of vaccination nationwide and by region after adjusting for variables. Results: Between 2009 and 2011, vaccination coverage increased to over 80% in Peru. In infants < 1 year of age, GE ambulatory cases, hospitalizations, and deaths decreased in the post-vaccination period by 40.3%, 46.2%, and 55.5%, respectively (and in children < 5 years of age, by 34.4%, 41.9%, and 54.3%, respectively) compared with the pre-vaccination period. Results of the multivariate time-trend analysis also found significant decreases in the post-vaccination period of 10.7% (GE ambulatory cases), 17.2% (GE hospitalizations), and 37.3% (GE mortality) in children < 5 years of age. Data analyzed by region varied, with Costa and Sierra regions generally in line with the national findings; however, some findings were less robust for Selva due to fewer available data. Conclusion: After 9 years of RV vaccination in Peru, there appears to be a statistically significant positive impact of vaccination, in terms of reducing GE-related mortality, hospitalizations, and ambulatory visits in infants and young children. For policymakers to understand regional differences and future vaccination needs, continued improvement in surveillance is needed. [ABSTRACT FROM AUTHOR]

Background Oligosaccharides are the third most abundant component in human milk. They are a potential protective agent against neonatal sepsis. Objectives We aimed to explore the association between human milk oligosaccharides (HMOs) and late-onset sepsis in very-low-birth-weight infants, and to describe the composition and characteristics of HMOs in Peruvian mothers of these infants. Methods This is a secondary data analysis of a randomized clinical trial. We conducted a retrospective cohort study of mothers and their very-low-birth-weight (<1500 g) infants with ≥1 milk sample and follow-up data for >30 d. HMOs were measured by high performance liquid chromatography (HPLC). We used factor analysis and the Mantel–Cox test to explore the association between HMOs and late-onset neonatal sepsis. Results We included 153 mother–infant pairs and 208 milk samples. Overall, the frequency of the secretor phenotype was 93%. Secretors and nonsecretors were defined by the presence and near-absence of α1-2-fucosylated HMOs, respectively. The most abundant oligosaccharides were 2'-fucosyllactose, lacto-N-fucopentaose (LNFP) I, and difucosyllacto-N-tetraose in secretors and lacto-N-tetraose and LNFP II in nonsecretors. Secretors had higher amounts of total oligosaccharides than nonsecretors (11.45 g/L; IQR: 0.773 g/L compared with 8.04 g/L; IQR: 0.449 g/L). Mature milk samples were more diverse in terms of HMOs than colostrum (Simpson's Reciprocal Diversity Index). We found an association of factor 3 in colostrum with a reduced risk of late-onset sepsis (HR: 0.63; 95% CI: 0.41, 0.97). Fucosyl-disialyllacto-N-hexose (FDSLNH) was the only oligosaccharide correlated to factor 3. Conclusions These findings suggest that concentrations of different HMOs vary from one individual to another according to their lactation period and secretor status. We also found that FDSLNH might protect infants with very low birth weight from late-onset neonatal sepsis. Confirming this association could prove 1 more mechanism by which human milk protects infants against infections and open the door to clinical applications of HMOs. This trial was registered at clinicaltrials.gov as NCT01525316. [ABSTRACT FROM AUTHOR]

Gastroenteritis in children is a serious condition in many parts of the world. Salmonella enterica is one of the causes of the disease. In this study, 280 fecal samples from children with diarrhea in four hospitals in Lima, Peru, were collected between September 2012 and March 2013. Salmonella was detected in 26 of the samples. Serotyping demonstrated that 25 of the isolates were S. enterica Infantis, and one isolate was S. enterica Typhimurium. Repetitive extragenic palindromic–polymerase chain reaction analysis suggests that all S. Infantis belong to the same clone. All but one of the S. Infantis isolates exhibited an extended-spectrum β-lactamase phenotype as they harbored bla CTX-M 65 . Two strains also carried bla TEM-1 . Nine of the isolates were resistant to azithromycin and two to ciprofloxacin. This study demonstrates that a multidrug-resistant S. Infantis clone carrying bla CTX-M 65 was circulating among children in Lima, Peru. The development of molecular epidemiology studies in Salmonella -causing diarrhea or other pathologies in Lima and in other areas will be useful to determine the permanence, geographical spread, and clinical implications of this clone. [ABSTRACT FROM AUTHOR]

Objective: To determine the effect of a fish protein isolate (FPi), administered over 6 months, on the growth of children aged 6-36 months, measured by Z-scores of height-for-age (HAZ) and weight-for-height (WHZ), compared with the standard meal without FPi; and to determine the safety and acceptability of FPi daily consumption.Design: Cluster-randomized community-based controlled trial. For 6 months, the centres received either FPi replacing 50 % of total proteins in the diet or standard protein. HAZ and WHZ were used to determine the effect on growth. Acceptability was determined by daily consumption, measured by weighing the servings before and after consumption.Setting: Day care centres and community nutritional centres in northern Lima, Peru.Subjects: Children (n 441) aged 6-36 months.Results: Four centres were randomized to the intervention with FPi, five centres were randomized to the standard control diet. More than 36 900 meals were prepared and administered in a supervised manner. Both groups received the same amounts of energy and proteins daily (proteins about 12-15 % of total energy). Growth of children who received the FPi diet was similar to that of children with the standard diet. Consumption was similar in the FPi and control groups (70 v. 80 % of amount offered, respectively). The protein was safe and well tolerated. No adverse events were reported. However, the cost of the intervention with FPi was 20-40 % lower v. the standard diet with animal protein derived from beef, chicken, eggs or liver.Conclusions: The FPi was well accepted and there was no significant difference in growth between both groups. FPi is a potential source of animal protein at lower cost. [ABSTRACT FROM AUTHOR]

Enteroaggregative Escherichia coli (EAEC) causes acute and persistent diarrhea among children, HIV-infected patients, and travelers to developing countries. We have searched for 18 genes-encoding virulence factors associated with aggregative adherence, dispersion, biofilm, toxins, serine protease autotransporters of Enterobacteriaceae (SPATEs) and siderophores, analyzed in 172 well-characterized EAEC strains (aggR +) isolated from stool samples of 97 children with diarrhea and 75 healthy controls from a passive surveillance diarrhea cohort study in Peru. Eighty-one different genetic profiles were identified, 37 were found only associated with diarrhea and 25 with control samples. The most frequent genetic profile was aggC + aatA + aap + shf + fyuA +, present in 19 strains, including diarrhea and controls. The profile set1A + set1B + pic + was associated with diarrhea (P < 0.05). Of all genes evaluated, the most frequent were aatA (CVD 342) present in 159 strains (92.4%) and fyuA in 157 (91.3%). When EAEC strains were analyzed as a single pathogen (excluding co-infections), only pic was associated with diarrhea (P < 0.05) and with prolonged diarrhea (diarrhea ≥ 7 days) (P < 0.05). In summary, this is the first report on the prevalence of a large set of EAEC virulence genes and its association with diarrhea in Peruvian children. More studies are needed to elucidate the exact role of each virulence factor. [ABSTRACT FROM AUTHOR]

EPEC is an attaching and effacing diarrheal pathogen that carries a large pathogenicity island, locus for enterocyte effacement (LEE). Recently, the pathogenicity island PAI O-122 was described among non-LEE effectors and found to be associated with diarrhea among atypical EPEC strains. It is unknown if incomplete PAI O-122 could be associated with diarrhea duration and severity. To identify these virulence determinants we analyzed 379 EPEC strains isolated from Peruvian children. EPEC was diagnosed by PCR(eae+, stx-) and classified as typical(t-EPEC) or atypical(a-EPEC). To characterize PAI O-122 we amplified three modules by PCR: Module 1( pagC ), Module 2( senA , nleB and nleE ) and Module 3( lifA/efa-1 ). To characterize the large ORF lifA/efa-1 we amplified the regions known as efa-N, efa-M and efa-C. Clinical information was obtained from the cohort study. A total of 379 EPEC strains were able to analyze PAI O-122 genes, 128 (10.4%) EPEC strains were isolated from 1235 diarrhea episodes and 251(9.2%) from 2734 healthy controls. t-EPEC strains were isolated from 14.8% (19/128) of children with diarrhea and 25/251(10.0%) from healthy controls. The most frequent PAI O-122 genes were nleE (37.7%), senA (34.6%) and nleB (37.5%), with similar prevalence among diarrhea and control samples. However, lifA/efa-1 was more common among diarrhea cases than healthy control cases (30.5% vs. 21.1%, p < 0.05). The presence of complete PAI O-122 was associated with diarrhea episodes of higher severity among single pathogen infection (33.3% vs. 1.8%, p < 0.05) mainly due to the presence of a complete lifA/efa- 1 gene. In summary, the gene lifA/efa-1 is significantly associated with diarrheal episodes of higher severity, suggesting to be an important virulent factor. [ABSTRACT FROM AUTHOR]

Diarrhea remains the third leading cause of death in children under ive years, despite recent advances in the management and prevention of this disease. It is caused by multiple pathogens, however, the prevalence of each varies by age group, geographical area and the scenario where cases (community vs hospital) are recorded. The most relevant pathogens in public health are those associated with the highest burden of disease, severity, complications and mortality. In our country, norovirus, Campylobacter and diarrheagenic E. coli are the most prevalent pathogens at the community level in children. In this paper we review the local epidemiology and potential areas of development in ive selected pathogens: rotavirus, norovirus, Shiga toxin-producing E. coli (STEC), Shigella and Salmonella. Of these, rotavirus is the most important in the pediatric population and the main agent responsible for child mortality from diarrhea. The introduction of rotavirus vaccination in Peru will have a signiicant impact on disease burden and mortality from diarrhea. However, surveillance studies are needed to determine the impact of vaccination and changes in the epidemiology of diarrhea in Peru following the introduction of new vaccines, as well as antibiotic resistance surveillance of clinical relevant bacteria. [ABSTRACT FROM AUTHOR]

Objectives. To describe physicians' preferences of antibiotic use in children less than 5 years in health centers of primary level in three periurban districts in Lima, Perú. Material and methods. A structured survey was applied to 218 general practitioners from three health networks of Lima. The survey included six typical clinical cases in children under 5 years with questions about antibiotic use: the cases were common cold, pharyngitis, pneumonia, bronchial obstructive syndrome, watery diarrhea and dysentery. Results. 81.6% of the physicians responded that more than a quarter of the patients they attended were children under five years. 15.6% of the general physicians would use an antibiotic for common cold treatment. For dysentery treatment 90.4% would use antibiotics, the frequently used were Trimethoprim-Sulfamethoxazole (TMP-SMX) and Furazolidone. 86.2% of physicians would recommend an antibiotic for pharyngitis. In a watery diarrhea case 32.7% of the doctors would use. In the case of bronchospasm, 73% of the doctors would recommend an antibiotic. 96.3% would recommend antibiotics for pneumonia. The perception of the degree of mother's satisfaction increased the risk of inappropriate prescription of antibiotics OR: 1.6, p=0.031, 95% CI: 1.1-2.6). Conclusions. There is tendency to overuse antibiotics for diagnoses such as pharyngitis and bronchospasm, as well as in cases of watery diarrhea and common cold, the reason could be that a large number of children under five years are treated by general practitioners without training in pediatric care. [ABSTRACT FROM AUTHOR]

Objectives. To determine the frequency and clinical features of central nervous system infections caused by enterovirus in children treated at the Hospital Nacional Cayetano Heredia in Lima, Peru. Materials and methods. A prospective, descriptive study was performed from April 2008 to March 2010. Patients aged 1 month -- 14 years with clinical diagnosis of encephalitis or aseptic meningitis were included. We investigated the presence of enterovirus, herpes simplex virus 1 (HSV-1), herpes simplex virus 2 (HSV-2) and varicella-zoster virus (VZV) by polymerase chain reaction (PCR). Results. 97 patients were included, out of which 69 % had acute encephalitis and 31 % acute meningitis. Enteroviruses were identified in 52,6% of all acute non-bacterial central nervous system infections; corresponding to 83,3 % of meningitis and 38,8 % of encephalitis. There were no cases of infection due to HSV-1, HSV-2 or VZV. Enterovirus infections reached 82,9 % in the warm months (November-January) and 28,6 % in the colder months (May-July). Conclusions. Enteroviruses are the principal etiologic agents in acute aseptic meningitis and encephalitis in pediatric patients in Lima, Peru. Enteroviruses have a seasonal epidemiological pattern with a clear increase in the number of cases during the summer months. It is useful to have this rapid diagnostic method available as an aid in the management of acute central nervous system infections. [ABSTRACT FROM AUTHOR]

Introduction. Diarrheagenic E. coli (DEC) are a major cause of diarrhea in children in developing countries. However, they are not part of routine diagnosis in clinical laboratories. Objectives. To determine the DEC prevalence in Peruvian children and to describe the genetic variability of these strains. Materials and methods. A total of 8 003 E. coli strains previously isolated from eight different studies of diarrhea in children, mainly from peri-urban areas of Lima, were analyzed. Diagnosis of DEC was done with Multiplex real-time PCR using genes for each of the 6 DEC groups. Conventional PCR was performed for the detection of additional virulence genes. Results. Globally, the mean prevalence in diarrhea samples (n=4,243) was: enteroaggregative E. coli (EAEC) 9.9%, enteropathogenic E. coli (EPEC) 8.5%, enterotoxigenic E. coli (ETEC) 6.9%, diffusely adherent E. coli (DAEC) 4.8%, Shiga toxin-producing E. coli (STEC) 0.8% and enteroinvasive E. coli (EIEC) 0.6%. The relative frequency of each pathogen varies according to the age and the type of study. The main pathotypes in control samples (n=3,760) were EPEC (10.9%) and EAEC (10.4%). An important variability in the virulence genes frequency and molecular resistance mechanisms for each pathotype was found, without differences between diarrhea and control groups. Conclusions. DEC are a major cause of diarrhea in Peruvian children. These pathogens are highly heterogeneous. Additional studies are required to determine the prevalence in rural areas of Peru and in severe diarrhea cases. [ABSTRACT FROM AUTHOR]

Objective. To determine the epidemiology of invasive pneumococcal disease (IPD) and the antibiotic susceptibility and serotype distribution of S. pneumoniae in pediatric patients in Lima, Peru. Methods. A 2-year, multicenter, passive surveillance study conducted from May 2006-April 2008 in 11 public hospitals and five private laboratories in Lima, Peru, in patients less than 16 years of age with sterile site cultures yielding S. pneumoniae. Antibiotic susceptibility was performed by Etest (AB Biodisk, Solna, Switzerland). Strains were serotyped by the Quellung reaction. Results. In all, 101 IPD episodes were studied, 68.3% of which were among children less than 24 months of age. Diagnoses were: pneumonia (47.5%), meningitis (38.6%), and sepsis (7.9%). The overall case fatality rate was 22.0%; case fatality rate in meningitis was 32.4%. While 80.0% of fatal cases were in those less than 24 months of age, only 50.7% of non-fatal cases (P < 0.05) were in this age group. Resistance rates were high for trimethoprim/sulfamethoxazole (76.2%), erythromycin (24.8%), and penicillin (22.8%). The most common serotypes were 14, 6B, 19F, 23F, and 5, which accounted for 69.7% of all strains and 87.0% of penicillin non-susceptible strains. Conclusion. IPD in hospitalized children in Lima is associated with high antimicrobial resistance levels and elevated case fatality rate, especially in young children. This baseline data will be useful for evaluating the effects of vaccine introduction. [ABSTRACT FROM AUTHOR]

Summary: Norovirus was detected in 17.4% of 224 diarrhoeal samples from children younger than 24 months of age in Lima, in whom all common pathogens had been excluded (pathogen negative). Norovirus was identified more frequently in children older than 12 months of age than in younger children (34% vs 8%, P <0.001). Among norovirus-positive samples, genogroup II was the predominant group (92%). Compared with rotavirus, norovirus episodes tended to be of shorter duration and less severe. The role of norovirus as a cause of diarrhoea and the ascertainment of its severity in developing countries needs further confirmation by future epidemiological studies. [ABSTRACT FROM AUTHOR]

• The frequency of pneumococcal nasopharyngeal carriage has decreased after PCV13 introduction. • The frequency of PCV13 serotypes has decreased after PCV13 introduction compared to the pre-PCV7 period. • Antimicrobial resistance in Streptococcus pneumoniae has increased after PCV13 compared to the pre-PCV7 period. To determinate the frequency of Streptococcus pneumoniae nasopharyngeal carriers, serotypes and antimicrobial resistance in healthy children in Lima, Peru, post-PCV13 introduction and to compare the results with a similar study conducted between 2006 and 2008 before PCV7 introduction (pre-PCV7). A cross-sectional multicenter study was conducted between January 2018 and August 2019 in 1000 healthy children under two years of age. We use standard microbiological methods to determinate S. pneumoniae from nasopharyngeal swab, Kirby Bauer and minimum inhibitory concentration methods to determinate antimicrobial susceptibility and whole genomic sequencing to determinate pneumococcal serotypes. The pneumococcal carriage rate was 20.8 % vs. 31.1 % in pre-PCV7 (p < 0.001). The most frequent serotypes were 15C, 19A and 6C (12.4 %, 10.9 % and 10.9 % respectively). The carriage of PCV13 serotypes after PCV13 introduction decreased from 59.1 % (before PCV7 introduction) to 18.7 % (p < 0.001). Penicillin resistance was 75.5 %, TMP/SMX 75.5 % and azithromycin 50.0 %, using disk diffusion. Penicillin resistance rates using MIC breakpoint for meningitis (MIC ≥ 0.12) increased from 60.4 % to 74.5 % (p = 0.001). The introduction of PCV13 in the immunization program in Peru has decreased the pneumococcal nasopharyngeal carriage and the frequency of PCV13 serotypes; however, there has been an increase in non-PCV13 serotypes and antimicrobial resistance. [ABSTRACT FROM AUTHOR]

The main aim of this study was to establish the resistance levels to antimicrobial agents, in 222 non-pathogenic E. Coli strains of fecal origin in Peru. The proportion of resistance found to the evaluated antimicrobials was ampicillin (62.6%), cotrimoxazole (48,6%), tetracycline (43,0%) and chloramphenicol (15,8%). We emphasize the high resistance levels found for quinolones: 32% for nalidixic acid (NAL) and 12% for ciprofloxacin (CIP). These high levels of quinolone-resistance in non-pathogenic strains isolated from children in this age group highlight the extensive use and the impact of the intake of this kind of antimicrobials in the community, showing the potential risk of the loss of their utility in the area. [ABSTRACT FROM AUTHOR]

The study described in this article evaluated sources of contamination of children's food and drinking water in rural households in the highlands of Peru. Samples from children's meals, drinking water, kitchen utensils, and caregivers' and children's hands were analyzed for total coliforms and E. coli counts using Petrifilm EC. Thermotolerant coliforms in water were measured using DelAgua test kits while diarrheagenic E. coli was identified using polymerase chain reaction methods (PCR). Thermotolerant coliforms were found in 48% of all water samples. E. coli was found on 23% of hands, 16% of utensils, and 4% of meals. Kitchen cloths were the item most frequently contaminated with total coliforms (89%) and E. coli (42%). Diarrheagenic E. coli was found in 33% of drinking water, 27% of meals, and on 23% of kitchen utensils. These findings indicate a need to develop hygiene interventions that focus on specific kitchen utensils and hand washing practices, to reduce the contamination of food, water, and the kitchen environment in these rural settings. [ABSTRACT FROM AUTHOR]

Objective. To describe the use of antibiotics in Peruvian children under 1 year in a setting where they are available without a prescription. Methods. Data were analyzed from a cohort study between September 2006 and December 2007 of 1 023 children < 2 months old in periurban Lima, Peru, followed until they were 1 year old. Results. Seven hundred seventy of 1 023 (75.3%) children took 2 085 courses of antibiotics. There were two courses per child per year (range 0-12). Higher rates of antibiotic use were found in children 3-6 months old (37.2%). Antibiotics were given to children for 8.2% of common colds, 58.6% of all pharyngitis, 66.0% of bronchitis, 40.7% of diarrheas, 22.8% of dermatitis, and 12.0% of bronchial obstructions. A physician's prescription was the most common reason for antibiotic use (90.8%). Medication use without a prescription was found in 6.9% of children, and in 63.9% of them it was preceded by a physician's prescription. Conclusions. Infants are often exposed to antibiotics in this setting. Overuse of antibiotics is common for diagnoses such as pharyngitis, bronchitis, bronchial obstruction, and diarrhea but is typically inappropriate (83.1% of courses) based on the most common etiologies for this age group. Interventions to improve the use of antibiotics should focus on physicians, since a physician's prescription was the most common reason for antibiotic use. [ABSTRACT FROM AUTHOR]

Introduction. Diffusely adherent E. coli (DAEC) is the sixth recognized group of diarrheagenic E. coli. However, its association with diarrhea remains controversial. Variability in the adherence patterns of clinical strains is unknown. Objectives. To compare the adherence patterns between strains isolated from children with and without diarrhea. Materials and methods. A total of 31 DAEC strains were analyzed, 25 from children with diarrhea and 6 from asymptomatic (control) children, isolated from a cohort study of children under one year of age in the southern districts of Lima. DAEC were identified by PCR (daaD gene). The pattern and adherence score in HEp-2 cell culture were evaluated, Actin polimerization was determined by fluorescence actin staining (fAS) and motility was evaluated by conventional microbiology methods. Results. Diffuse adherence pattern was found in 88% of diarrhea samples and in the total of control strains. The number of bacteria adhered per cell was significantly lower in diarrhea samples (p<0.05). However, actin polymerization was greater in diarrhea samples (60% vs. 17%). Motility test was positive in 60% of the diarrhea samples and in all control samples. Conclusions. Our findings suggest a difference between adherence patterns, actin polymerization and motility between DAEC strains corresponding to diarrhea and control groups. The significance of these results must be confirmed with a bigger number of strains and determining the presence of virulence genes in the strains. [ABSTRACT FROM AUTHOR]

Species of the Acinetobacter calcoaceticus-Acinetobacter baumannii complex are important human pathogens which can be recovered from animals and food, potential sources for their dissemination. The aim of the present study was to characterise the Acinetobacter isolates recovered from market meat samples in Peru. From July through August 2012, 138 meat samples from six traditional markets in Lima were cultured in Lysogeny and Selenite broths followed by screening of Gram-negative bacteria in selective media. Bacterial isolates were identified by MALDI-TOF MS and DNA-based methods and assessed for their clonal relatedness and antimicrobial susceptibility. Twelve Acinetobacter isolates were recovered from calf samples. All but one strain were identified as members of the clinically-relevant Acinetobacter calcoaceticus-Acinetobacter baumannii complex: 9 strains as Acinetobacter pittii , 1 strain as A. baumannii , and 1 strain as the recently described novel species A. dijkshoorniae. The remaining strain could not be identified at the species level unambiguously but all studies suggested close relatedness to A. bereziniae. All isolates were well susceptible to antibiotics. Based on macrorestriction analysis, six isolates were further selected and some of them were associated with novel MLST profiles. The presence of pathogenic Acinetobacter species in human consumption meat might pose a risk to public health as potential reservoirs for their further spread into the human population. Nevertheless, the Acinetobacter isolates from meat found in this study were not multidrug resistant and their prevalence was low. To our knowledge, this is also the first time that the A. dijkshoorniae species is reported in Peru. • 12 Acinetobacter spp. isolates were recovered in meat samples from 2 markets in Peru. • All but 1 strain were identified as species of the clinically-relevant ACB complex. • All isolates were highly susceptible to antimicrobial agents. • Market meat stands as a potential source of pathogenic Acinetobacter species. • The novel species A. dijkshoorniae was reported in Peru for the first time. [ABSTRACT FROM AUTHOR]

In pediatric patients, the antibiotic use is affected by parental beliefs and practices; especially in countries where it is possible to acquire them without prescription. This study aims to describe the knowledge, attitudes, and practices on antibiotic use among parents of children from urban and peri-urban health care centers in Lima. A cross-sectional study was performed at 1 urban and 2 peri-urban health care centers selected in Lima, Perú. Parents of children below the age of 3 years answered a knowledge-attitudes-practices-validated questionnaire about antibiotic use and were categorized as high, moderate, and low knowledge regarding antibiotics. We analyzed potential determinants for low knowledge and having medicated their children with unprescribed antibiotics using bivariate and multivariate analyses. A total of 224 parents were enrolled, and 8% were categorized as low knowledge. Half of the parents could not recognize that antibiotics cannot cure viral infections, 59.4% disagreed with "antibiotics speed up recovery from a cold," and 53.2% stored antibiotics at home. Remarkably 23.5% of parents reported having medicated their children with antibiotics without prescription, which was associated with belonging to the peri-urban health care center, use of antibiotics by their children in the last 12 months, and having purchased antibiotics without physicians' prescription. An alarming overuse of antibiotics without prescription was described among children below the age of 3 years. Educational interventions, addressing parental attitudes and practices, and health policies should be developed to limit inappropriate antibiotic use especially in peri-urban communities. [ABSTRACT FROM AUTHOR]

Background: The Pneumococcal conjugate vaccine (PCV) has decreased cases of invasive pneumococcal disease (IPD) worldwide. However, the impact of PCVs introduction may be affected by the serotype distribution in a specific context., Methods: Cross-sectional multicenter passive surveillance study of IPD cases in pediatric patients hospitalized in Lima, Peru between 2016 and 2019 (after PCV13 introduction) to determine the serotype distribution and antimicrobial resistance of Streptococcus pneumoniae. Serotyping was performed by a sequential multiplex PCR and confirmed by whole genome sequencing., Results: Eighty-five S. pneumoniae isolates were recovered (4.07/100,000 among children <60 months of age). Serotype 19A was the most common (49.4%). Children infected with serotype 19A in comparison with children infected with other serotypes were younger, had a lower rate of meningitis and higher rates of pneumonia, complicated pneumonia and antimicrobial resistance; 28.6% of patients with serotype 19A have received at least one dose of PCV13 vs. 62.8% of patients with other serotypes. Using MIC-breakpoints, 81.2% (56/69) of non-meningitis strains and 31.2% (5/16) of meningitis strains were susceptible to penicillin; 18.8% (3/16) of meningitis strains had intermediate resistance to ceftriaxone. Resistance to azithromycin was 78.8% (67/85). Serotype 19A frequency increased over time in the same study population, from 4.2% (4/96) in 2006-2008, to 8.6% (5/58) in 2009-2011, to 49.4% (42/85) in the current study (2016-2019) (p < 0.001)., Conclusions: After PCV13 introduction in Peru, serotype 19A remains the most prevalent; however, the vaccination coverage is still not optimal. Therefore, additonal surveillance studies are needed to determine the remaining IPD burden., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Importance: Previous studies have suggested that oral lactoferrin enhances diversity in the gut microbiota in infants while inhibiting the growth of opportunistic pathogens. However, the effect of lactoferrin on infant gut microbiota over time has yet to be thoroughly studied. Our study suggests that lactoferrin oral treatment in infants aged 12-18 months does not affect gut microbiome diversity and composition over time. To our knowledge, this is the first study to report the effect of lactoferrin on infant gut microbiome composition over time and helps elucidate its impact on infant health and its therapeutic potential., Competing Interests: The authors declare no conflict of interest.

Enterotoxigenic Escherichia coli (ETEC) ranks among the most relevant diarrheagenic pathogens. Efforts to design vaccines to fight ETEC have been focused on colonizing factors (CFs) and atypical virulence factors (AVF). An effective vaccine must account for differences in the regional prevalence of these CFs and AVFs to be truly effective in a given area. In the present study, the presence of 16 CFs and 9 AVFs, as well as the heat-stable (ST) variants (STh or STp), was established by polymerase chain reaction in 205 Peruvian ETEC isolates (120 from diarrhea cases and 85 from healthy controls). Ninety-nine (48.3%) isolates were heat-labile, 63 (30.7%) ST, and 43 (21.0%) presented both toxins. Of ST isolates, 59 (28.8%) possessed STh, 30 (14.6%) STp, five (2.4%) both STh and STp, and 12 (5.8%) were not amplified for any variant tested. The presence of CFs was associated with diarrhea (P < 0.0001). The presence of eatA as well as concomitant presence of CSI, CS3, and CS21 and of C5 and C6 was statistically related to diarrhea cases. The present results suggests that, if effective, a vaccine considering CS6, CS20, and CS21, together with EtpA, would provide protection against 64.4% of the isolates analyzed, whereas the addition of CS12 and EAST1 would lead to 83.9% coverage. Large studies are needed to establish both the ideal candidates to be considered to develop a vaccine effective in the area, and continuous surveillance is needed to detect displacement of circulating isolates that may compromise future vaccines.

Background: The increasing prevalence of drug-resistant Neisseria gonorrhoeae (NG) infections has caused great concern. Ciprofloxacin remains the empiric antimicrobial recommended to treat NG infections in Peru disregarding the susceptibility profile of circulating NG strains. We report the prevalence of individuals infected with NG strains presenting mutations in the gyrA gene that confers ciprofloxacin resistance., Methods: We conducted a descriptive study assessing extragenital swab samples collected from a cohort of men who have sex with men and transgender women in Lima, Peru. Anal and pharyngeal NG positive swabs for Aptima Combo 2 assay (Hologic Inc., USA) were used for DNA extraction. We performed TaqMan real time PCR assays to detect a point mutation at codon Ser91 of the gyrase A ( gyr A) gene., Results: From 156 individuals who had at least one positive sample for NG reported by the Aptima assay, 80 individuals had at least one amplified DNA for the gyrA gene. We found that 67 of them (84.0%) were infected with a gyrA -mutated NG strain at the Ser91 codon., Conclusions: We report a high prevalence of gyrA mutation conferring ciprofloxacin resistance among individuals with extragenital NG infection. Empirical treatment of NG needs to be urgently updated in Peru in concordance with international guidelines.

Class 1 and Class 2 integrons are mobilizable elements able to carry a variety of antibiotic resistance determinants. In the present study, Class 1 and 2 integrons present in 355 pathogenic Escherichia coli (285 diarrheagenic, of these 129 were enteropathogenic, 90 enteroaggregative, 66 enterotoxigenic, and 70 bacteremic) isolated from healthy and ill children under age 5 from periurban areas of Lima, Peru, were characterized. The presence of integrase 1 and 2 was established by polymerase chain reaction (PCR), and variable regions were grouped by PCR-restriction fragment length polymorphism and subsequent sequencing. Antimicrobial resistance was established by disk diffusion. Ninety-seven isolates (27.3%) presented integrase 1, and 16 (4.5%) presented integrase 2 (P < 0.0001); in addition, seven (2.0%) isolates, six diarrheagenic and one bacteremic, presented both integrase genes. The presence of integrase 1 was more frequent among bacteremic isolates (P = 0.0004). Variable regions were amplified in 76/120 (63.3%) isolates with up to 14 gene arrangements. The most prevalent gene cassettes were those encoding dihydrofolate reductases as well as aminoglycoside modifying enzymes. Of note, Class 1 integrons tended to be associated with the presence of extended-spectrum β-lactamases (ESBLs). A variety of Class 1 and 2 integrons were detected in diarrheagenic and bacteremic E. coli, demonstrating the heterogeneity of variable regions circulating in the area. The association of integrons with ESBLs is worrisome and has an impact on the development of multidrug resistance.

Objectives: To provide original data on Pneumocystis primary infection in non-immunosuppressed infants from Peru., Methods: A cross sectional study was performed. Infants less than seven months old, without any underlying medical conditions attending the "well baby" outpatient clinic at one hospital in Lima, Peru were prospectively enrolled during a 15-month period from November 2016 to February 2018. All had a nasopharyngeal aspirate (NPA) for detection of P. jirovecii DNA using a PCR assay, regardless of respiratory symptoms. P. jirovecii DNA detection was considered to represent pulmonary colonization contemporaneous with Pneumocystis primary infection. Associations between infants' clinical and demographic characteristics and results of P. jirovecii DNA detection were analyzed., Results: P. jirovecii DNA was detected in 45 of 146 infants (30.8%) and detection was not associated with concurrent respiratory symptoms in 40 of 45 infants. Infants with P. jirovecii had a lower mean age when compared to infants not colonized (p <0.05). The highest frequency of P. jirovecii was observed in 2-3-month-old infants (p < 0.01) and in the cooler winter and spring seasons (p <0.01). Multivariable analysis showed that infants living in a home with ≤ 1 bedroom were more likely to be colonized; Odds Ratio =3.03 (95%CI 1.31-7.00; p = 0.01)., Conclusion: Pneumocystis primary infection in this single site in Lima, Peru, was most frequently observed in 2-3-month-old infants, in winter and spring seasons, and with higher detection rates being associated with household conditions favoring close inter-individual contacts and potential transmission of P. jirovecii., (Copyright © 2021 SFMM. All rights reserved.)

The aim of the study was to determine the frequency of six genes encoding serine protease autotransporter proteins Enterobacteriaceae (SPATE) in diffusely adherent Escherichia coli (DAEC) isolates from children with (WD, n=63) and without diarrhea (WOD, n=41) from Lima, Peru. WOD were considered a control group. For the detection of the genes, 2 multiple PCRs were standardized: triple A (sigA, pet, espP) and triple B (sat, pic, espC). In both groups, the most frequent SPATE gene was Sat (39.7% of WD and 41.5% of WOD), followed by spP (20.6% and 9.7% in WD and WOD respectively). The other genes were detected in proportions lower than 10.0%, in the following order of frequency: pet, sigA, espC and pic, without significant differences between the groups. It was concluded that Sat is the most frequent SPATE in DAEC and that these strains may possess SPATE genes regardless of whether they are isolated in WD or WOD.

Data on features of Pneumocystis primary infection in infancy are still fragmented. To study Pneumocystis primary infection, 192 infants who were monitored for acute pulmonary disease or fever over a 40-month period were retrospectively investigated. P. jirovecii detection on archival nasopharyngeal aspirates was performed using a qPCR assay. Factors associated with P. jirovecii were assessed using univariate and multivariate analyses. P. jirovecii genotypes in infants and a control group of adults contemporaneously diagnosed with Pneumocystis pneumonia were identified using unilocus, bilocus, and multilocus sequence typing (MLST). P. jirovecii was detected in 35 infants (18.2%). The univariate analysis pointed out four factors: viral infection (P = .035, OR [IC 95], 2.2 [1.1-4.7]), lower respiratory tract infection (P = .032, OR [IC 95], 2.5 [1.1-5.9]), absence of hospital discharge after birth (P = .003, OR (IC 95), 0.1 (0.02-0.5]), and the 63-189-day group (P < .001, OR [IC 95], 42.2 [5.4-332]). The multivariate analysis confirmed these two latter factors (P = .02, OR [IC 95], 0.1 [0.02-0.72]; P = .005, OR [IC 95], 11.5 [2.1-63.5]). Thus, P. jirovecii acquisition mostly takes place in the community. A comparison of these data with those of previously published studies showed that median and interquartile range of positive-infant ages were close to those observed in Chile, Denmark, and Peru, highlighting similar characteristics. Common unilocus or bilocus genotypes were identified in infants and adults, whereas no MLST genotypes were shared. Therefore, a common reservoir made up of infected infants and adults is still hypothetical. Finally, primary infection is a worldwide phenomenon occurring at the same time in childhood regardless of geographical location, rather than an incidental event., (© The Author(s) 2019. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

The mechanisms of resistance to nitrofurans from 18 meat samples with Salmonella enterica (chicken: 15; beef: 2; pork: 1) collected in Lima (Peru) were analyzed. The isolates were serotyped and the susceptibility levels to furazolidone and nitrofurantoin [with and without the efflux pump inhibitor Phenyl-Arginine- β-naphthylamide (PAβN)], the presence of mutations in the snrA and cnr genes and the transferability of resistance by conjugation were established. Fifteen samples with S. infantis (13 from chicken samples), 2 with S. enteritidis and 1 with S. anatum were identified. All isolates except the S. anatum were resistant to both nitrofurans showing MICs (minimum inhibitory concentration) of furazolidone and nitrofurantoin of 32-64 μg/mL and 128-256 μg/mL, respectively. The addition of PAßN had no effect on the MIC levels. All nitrofuran-resistant isolates showed amino acid codon alterations at both snrA and cnr (S. infantis: snrA STOP-151; cnr STOP-137; S. enteritidis: snrA STOP-180; cnr STOP-179). No transferable mecha nisms of nitrofuran resistance were detected.

Stunting, defined as height-for-age Z score equal to or lower than -2, is associated with increased childhood mortality, cognitive impairment, and chronic diseases. The aim of the study was to investigate the relationship between linear growth, intestinal damage, and systemic inflammation in infants at risk of stunting. We followed up 78 infants aged 5-12 months living in rural areas of Peru for 6 months. Blood samples for biomarkers of intestinal damage (intestinal fatty-acid-binding protein [I-FABP] and zonulin) and systemic inflammation (interleukin-1β, interleukin-6, tumor necrosis factor α [TNF-α], soluble CD14, and lipopolysaccharide-binding protein [LBP]) and fecal samples for microbiome analysis were collected at baseline and closure of the study. The children's growth and health status were monitored through biweekly home visits by trained staff. Twenty-one percent of the children became stunted: compared with non-stunted children, they had worse nutritional parameters and higher levels of serum I-FABP at baseline. The likelihood of becoming stunted was strongly associated with an increase in sCD14 over time; LBP and TNF-α showed a trend toward increase in stunted children but not in controls. The fecal microbiota composition of stunted children had an increased beta diversity compared with that of healthy controls throughout the study. The relative abundance of Ruminococcus 1 and 2 , Clostridium sensu stricto , and Collinsella increased in children becoming stunted but not in controls, whereas Providencia abundance decreased. In conclusion, stunting in our population was preceded by an increase in markers of enterocyte turnover and differences in the fecal microbiota and was associated with increasing levels of systemic inflammation markers.

Background: Until recently, Zika virus (ZIKV) infections were considered mild and self-limiting. Since 2015, they have been associated with an increase in microcephaly and other birth defects in newborns. While this association has been observed in case reports and epidemiological studies, the nature and extent of the relationship between ZIKV and adverse pregnancy and pediatric health outcomes is not well understood. With the unique opportunity to prospectively explore the full spectrum of issues related to ZIKV exposure during pregnancy, we undertook a multi-country, prospective cohort study to evaluate the association between ZIKV and pregnancy, neonatal, and infant outcomes., Methods: At research sites in ZIKV endemic regions of Brazil (4 sites), Colombia, Guatemala, Nicaragua, Puerto Rico (2 sites), and Peru, up to 10,000 pregnant women will be recruited and consented in the first and early second trimesters of pregnancy and then followed through delivery up to 6 weeks post-partum; their infants will be followed until at least 1 year of age. Pregnant women with symptomatic ZIKV infection confirmed by presence of ZIKV RNA and/or IgM for ZIKV will also be enrolled, regardless of gestational age. Participants will be tested monthly for ZIKV infection; additional demographic, physical, laboratory and environmental data will be collected to assess the potential interaction of these variables with ZIKV infection. Delivery outcomes and detailed infant assessments, including physical and neurological outcomes, will be obtained., Discussion: With the emergence of ZIKV in the Americas and its association with adverse pregnancy outcomes in this region, a much better understanding of the spectrum of clinical outcomes associated with exposure to ZIKV during pregnancy is needed. This cohort study will provide information about maternal, fetal, and infant outcomes related to ZIKV infection, including congenital ZIKV syndrome, and manifestations that are not detectable at birth but may appear during the first year of life. In addition, the flexibility of the study design has provided an opportunity to modify study parameters in real time to provide rigorous research data to answer the most critical questions about the impact of congenital ZIKV exposure., Trial Registration: NCT02856984 . Registered August 5, 2016. Retrospectively registered.

Antibiotic resistance is a major global problem. The objective of this study was to determine antibiotic resistance in commensal strains isolated from healthy children from rural communities of Moyobamba and Urubamba in Peru. This cohort study identified 179 commensal E. coli strains from 93 children, followed for six months. Thirteen antibiotics were analyzed by diffusion disk. The highest rates of resistance were for cotrimoxazole (49.1%), ampicillin (48.0%), and nalidixic acid (31.8%). An 11.6% increase in resistance was found for nalidixic acid and 6.4% for cotrimoxazole in this period; while 34.0% of the isolates were multidrug-resistant. This study supports previous findings of multidrug resistance in commensal strains in rural communities and highlights the increased rates of resistance over time. We recommend studies in larger populations with a longer follow-up.

To describe the frequency and severity of intraventricular hemorrhage and periventricular leukomalacia in low birth-weight neonates in three hospitals in Lima, Peru, 385 newborn babies weighing under 2,000 g at birth were evaluated between May 2012 and July 2014. Brain ultrasounds were obtained at 40 weeks' gestation, 3-5 days of life, and 3-4 weeks of life. Intraventricular hemorrhage occurred in 19.2% of neonates weighing under 1,500 g and was severe (grade III or with periventricular hemorrhagic infarction) in 9.6% of neonates under 1,500 g. Mortality in infants with intraventricular hemorrhage was 47.1%, while periventricular leukomalacia was found in 5.4% of neonates 1,500 g and under; both diagnoses were more frequent in lower-weight babies. The frequency of intraventricular hemorrhage is similar to that reported in other countries; however, severity and mortality are greater.

Background: Neonatal sepsis is a leading cause of child morbidity and mortality, especially in premature and low birth weight infants. Prompt antibiotic therapy is warranted, but its inappropriate use leads to bacterial resistance and adverse outcomes. Our objective is to describe the antibiotic use for late-onset sepsis in Peruvian premature infants., Methods: This study is a prospective study as a secondary analysis of a clinical trial in 3 neonatal care units in Peru. We included infants in the first 72 hours of life, with birth weight (BW) <2000 g. We described the antibiotic use as length of therapy (LOT) per 1000 patient days (PD) and antibiotic courses., Results: We included 408 neonates, with 12,204 PD of follow-up; 253 infants (62%) had a BW ≤1500 g. Total antibiotic use for late-onset sepsis was 2395 LOT (196 LOT/1000 PD). Two-hundred and seventy-one patients (66.4%) did not receive antibiotics for late-onset sepsis during their hospitalization. In total, 204 antibiotic courses were administered; 92 infants (22.5%) received 1 course, and 45 (11.0%) received 2-5 antibiotic courses. Mean duration of antibiotic course was 10.8 days (standard deviation: ±7.3). We found a significant association between a lower BW and increased antibiotic use per day (P < 0.001). The most commonly used antibiotics were vancomycin (143 LOT/1000 PD), carbapenems (115 LOT/1000 PD), aminoglycosides (72 LOT/1000 PD) and ampicillin (41 LOT/1000 PD)., Conclusions: Premature infants receive antibiotics for longer than recommended periods of time. Antibiotic overuse is greater in neonates with lower BW. Vancomycin is the most used antibiotic. There is an urgent need to develop antimicrobial stewardship programs in our setting.

Objective.: The objective of this study was to describe the presence of Enterobacteriaceae in meat samples collected in traditional markets of Lima and to establish the levels of antimicrobial resistance and the presence of extended spectrum beta-lactamases (BLEE) and AmpC in Escherichia coli., Materials and Methods.: A total of 138 meat samples, 64 (46.4%) chicken, 44 (31.9%) beef and 30 (21.7%) pork were collected. The isolated bacteria belonged to 17 different genera and, specifically, 14 were classified as Enterobacteriaceae. Sensitivity to ten antimicrobial agents was analyzed using the Kirby-Bauer disc diffusion method, BLEE and AmpC were determined by double disc and imipenem-ceftazidime induction tests, respectively., Results.: Antimicrobial resistance levels were high against trimethoprim-sulfamethoxazole, ampicillin, tetracycline, nalidixic acid, ciprofloxacin and chloramphenicol. There are significant differences in antibiotic resistance levels depending on the type of meat (chicken, beef and pork) (p <0.05). Multiple drug resistance (MDR) levels were particularly high in chicken and pork (98.2% and 86.4%, respectively). In addition, the presence of BLEE in Escherichia coli isolated from chicken meat was 59.4%., Conclusions.: Multiple drug resistance levels were high compared to antibiotics frequently used in humans; chicken and beef are highlighted as potential reservoirs of BLEE and pAmpC-producing Escherichia coli, respectively.

The presence of 25 virulence genes (VGs), genetic phylogroups, quinolone-resistance and Extended Spectrum β-lactamase (ESBL)-production was assessed in 65 Escherichia coli isolates from blood cultures in children <5 years in Peru. The most frequent VGs were fimA (89.2%), iutA (83.1%), agn43 (72.3%), iucA (67.7%), and fyuA (49.2%). The isolates belonged to D (47.7%), A (26.1%), B1 (21.5%), and B2 (4.6%) phylogroups. D + B2 isolates presented a high number of fimA, hly, papC, sat, and fyuA genes. Quinolone-susceptible (22 isolates - 33.8%) and ESBL-negative (31 isolates - 47.7%) isolates carried more VGs that their respective counterparts (5.7 vs. 4.7 and 5.3 vs. 4.4 respectively); the frequency of the fyuA, aat, aap, and hly genes significantly differed between quinolone-resistant and quinolone-susceptible isolates. Neonatal sepsis isolates tended to be more quinolone-resistant (P = 0.0697) and ESBL-producers (P = 0.0776). Early-onset neonatal sepsis isolates possessed a high number of VGs (5.2 VGs), especially in neonates of ≤1 day (5.9 VGs)., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Antibiotic resistance is increasing worldwide, being of special concern in low- and middle-income countries. The aim of this study was to determine the antimicrobial susceptibility and mechanisms of resistance in 205 enterotoxigenic Escherichia coli (ETEC) isolates from two cohort studies in children <24 months in Lima, Peru., Methods: ETEC were identified by an in-house multiplex real-time PCR. Susceptibility to 13 antimicrobial agents was tested by disk diffusion; mechanisms of resistance were evaluated by PCR., Results: ETEC isolates were resistant to ampicillin (64%), cotrimoxazole (52%), tetracycline (37%); 39% of the isolates were multidrug-resistant. Heat-stable toxin producing (ETEC-st) (48%) and heat-labile toxin producing ETEC (ETEC-lt) (40%) had higher rates of multidrug resistance than isolates producing both toxins (ETEC-lt-st) (21%), p<0.05. Only 10% of isolates were resistant to nalidixic acid and none to ciprofloxacin or cefotaxime. Ampicillin and sulfamethoxazole resistance were most often associated with blaTEM (69%) and sul2 genes (68%), respectively. Tetracycline resistance was associated with tet(A) (49%) and tet(B) (39%) genes. Azithromycin inhibitory diameters were ≤15 mm in 36% of isolates, with 5% of those presenting the mph(A) gene., Conclusions: ETEC from Peruvian children are often resistant to older, inexpensive antibiotics, while remaining susceptible to ciprofloxacin, cephalosporins and furazolidone. Fluoroquinolones and azithromycin remain the drugs of choice for ETEC infections in Peru. However, further development of resistance should be closely monitored., (Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: Lactoferrin (LF) is a broad-spectrum antimicrobial and immunomodulatory milk glycoprotein., Objective: To determine the effect of bovine LF on the prevention of the first episode of late-onset sepsis in Peruvian infants., Methods: We conducted a pilot randomized placebo-controlled double blind study in infants with a birth weight (BW) less than 2500g in 3 Neonatal Units in Lima. Patients were randomized to receive bovine LF 200mg/kg/d or placebo for 4 weeks., Results: One hundred and ninety neonates with a BW of 1591 ± 408 g and a gestational age of 32.1 ± 2.6 weeks were enrolled. Overall, 33 clinically defined first late-onset sepsis events occurred. The cumulative sepsis incidence in the LF group was 12/95 (12.6%) versus 21/95 (22.1%) in the placebo group, and 20% (8/40) versus 37.5% (15/40) for infants less than or equal to 1500 g. The hazard ratio of LF, after adjustment by BW, was 0.507 (95% CI: 0.249-1.034). There were 4 episodes of culture-proven sepsis in the LF group versus 4 in the placebo group. Considering that children did not received the intervention until the start of oral or tube feeding, we ran a secondary exploratory analysis using time since the start of the treatment; in this model, LF achieved significance. There were no serious adverse events attributable to the intervention., Conclusions: Overall sepsis occurred less frequently in the LF group than in the control group. Although the primary outcome did not reach statistical significance, the confidence interval is suggestive of an effect that justifies a larger trial.

The study was aimed to describe the serotype, mechanisms of antimicrobial resistance, and virulence determinants in Shigella spp. isolated from Peruvian children. Eighty three Shigella spp. were serogrouped and serotyped being established the antibiotic susceptibility. The presence of 12 virulence factors (VF) and integrase 1 and 2, along with commonly found antibiotic resistance genes was established by PCR. S. flexneri was the most relevant serogroup (55 isolates, 66%), with serotype 2a most frequently detected (27 of 55, 49%), followed by S. boydii and S. sonnei at 12 isolates each (14%) and S. dysenteriae (four isolates, 5%). Fifty isolates (60%) were multi-drug resistant (MDR) including 100% of S. sonnei and 64% of S. flexneri. Resistance levels were high to trimethoprim-sulfamethoxazole (86%), tetracycline (74%), ampicillin (67%), and chloramphenicol (65%). Six isolates showed decreased azithromycin susceptibility. No isolate was resistant to nalidixic acid, ciprofloxacin, nitrofurantoin, or ceftriaxone. The most frequent resistance genes were sul2 (95%), tet(B) (92%), cat (80%), dfrA1 (47%), blaOXA-1like (40%), with intl1 and intl2 detected in 51 and 52% of the isolates, respectively. Thirty-one different VF profiles were observed, being the ipaH (100%), sen (77%), virA and icsA (75%) genes the most frequently found. Differences in the prevalence of VF were observed between species with S. flexneri isolates, particularly serotype 2a, possessing high numbers of VF. In conclusion, this study highlights the high heterogeneity of Shigella VF and resistance genes, and prevalence of MDR organisms within this geographic region., (Copyright © 2015 Elsevier GmbH. All rights reserved.)

We evaluated the monthly distribution of rotavirus diarrhea in a cohort of children 12-24 months of age followed as part of a diarrhea clinical trial in a peri-urban community of Lima. We observed a peak of rotavirus diarrhea in the winter months and a decrease in rotavirus prevalence after the introduction of the rotavirus vaccine in Peru., (© The American Society of Tropical Medicine and Hygiene.)

Objective: There is little information about vaccine schedule compliance in very-low-birth-weight infants in developing countries. The aim of the study was to describe the compliance with the vaccine schedule among this population in Lima, Peru., Patients and Methods: We conducted a prospective cohort study in four hospitals in Lima in infants with a birth-weight of less than 1500 g, followed from birth up to 12 months of age every 2 weeks. The date and age at administration of each vaccine was recorded, Results: 222 infants were enrolled. The median birth-weight was 1250 g (range 550-1499 g) and the median gestational age was 30.0 weeks (range 23-37 weeks). The mean age for the first pentavalent (DPT, Hib, HepB) and oral polio vaccine administration was 4.3 ± 1.4 months in infants with a birth-weight of < 1000 g vs. 3.1 ± 1.0 in infants with a birth-weight 1000-1500 g (p < 0.001); 4.1 ± 0.9 vs. 3.3 ± 1.1 for rotavirus (p < 0.05); and 5.1 ± 2.1 vs. 4.3 ± 1.8 for the 7-valent pneumococcal conjugated vaccine. Only 35% had received the three doses of oral polio and pentavalent vaccine by seven months, although by nine months 81% had received these vaccines., Conclusions: Vaccination of very-low-birth-weight infants in Peru is significantly delayed, especially in infants with a birth-weight of < 1000 g and lower gestational age. Urgent educational interventions targeting physicians and nurses should be implemented in order to improve vaccination rates and timing in these high risk populations., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Conventionally, in Escherichia coli, phylogenetic groups A and B1 are associated with commensal strains while B2 and D are associated with extraintestinal strains. The aim of this study was to evaluate diarrheagenic (DEC) and commensal E. coli phylogeny and its association with antibiotic resistance and clinical characteristics of the diarrheal episode. Phylogenetic groups and antibiotic resistance of 369 E. coli strains (commensal strains and DEC from children with or without diarrhea) isolated from Peruvian children <1 year of age were determined by a Clermont triplex PCR and Kirby-Bauer method, respectively. The distribution of the 369 E. coli strains among the 4 phylogenetic groups was A (40%), D (31%), B1 (21%), and B2 (8%). DEC-control strains were more associated with group A while DEC-diarrhea strains were more associated with group D (P < 0.05). There was a tendency (P = 0.06) for higher proportion of persistent diarrhea (≥ 14 days) among severe groups (B2 and D) in comparison with nonsevere groups (A and B1). Strains belonging to group D presented significantly higher percentages of multidrug resistance than the rest of the groups (P > 0.01). In summary, DEC-diarrhea strains were more associated with group D than strains from healthy controls.

We conducted a prospective cohort study in four hospitals in Lima, Peru in infants with a birth weight ≤ 1,500 g followed from birth hospital discharge up to 1 year of age to determine the incidence of respiratory syncytial virus (RSV) hospitalizations. We enrolled 222 infants from March of 2009 to March of 2010: 48 infants with a birth weight < 1,000 g and 174 infants with a birth weight of 1,000-1,500 g (birth weight = 1,197 ± 224 g; gestational age = 30.1 ± 2.6 weeks). There were 936 episodes of respiratory infections; the incidence of respiratory infections during the first 1 year of life was 5.7 episodes/child-years. The incidence of RSV respiratory infections that required emergency room management was 103.9 per 1,000 child-years, and the incidence of RSV hospitalizations was 116.2 per 1,000 child-years (244.9 in infants with a birth weight < 1,000 g and 88.9 in infants 1,000-1,500 g; P < 0.05). The incidence of RSV respiratory infections that required emergency management or hospitalization is high among pre-mature infants in Lima., (© The American Society of Tropical Medicine and Hygiene.)

Childhood diarrhea is an important cause of malnutrition, which can be worsened when caretakers limit nutritional support. We queried 390 caregivers and their children in a peri-urban community in Lima, Peru regarding general perceptions of feeding and feeding practices during diarrhea. Overall, 22.1% of caregivers perceived feeding during diarrhea to be harmful. At baseline, 71.9% of caregivers would discontinue normal feeding or give less food. Most would withhold milk, eggs, and meats. Approximately 40% of caregivers would withhold vegetables and fruits. A pilot educational intervention was performed to improve feeding during diarrhea. At follow-up survey 3 months later, none of the caregivers would recommend withholding food. Only 23.2% would recommend discontinuing normal feeding and 1.8% perceived food to be damaging. Misperceptions of the role of feeding during diarrhea pose a significant health risk for children, but a simple educational intervention might have a major impact on these perceptions and practices., (© The American Society of Tropical Medicine and Hygiene.)

Objectives: To determine the pattern of antibiotic susceptibility of isolated Streptococcus pneumoniae strains of healthy nasopharyngeal carriers younger than 2 years in seven regions of Peru., Materials and Methods: Between 2007 and 2009, nasopharyngeal swab samples were collected among 2123 healthy children aged 2-24 months in growth and development medical practices (CRED) and vaccination offices of hospitals and health centers in Lima, Piura, Cusco, Abancay, Arequipa, Huancayo, and Iquitos. The resistance to ten antibiotics through disk diffusion sensitivity testing of isolated pneumococcus strains was determined., Results: 572 strains were isolated. High rates of resistance to co-trimoxazole (58%), penicillin (52.2% non-sensitive); tetracycline (29,1%); azithromycin (28,9%), and erythromycin (26,3%). Resistance to chloramphenicol was low (8.8%). Multiresistance was found at 29.5%. Resistance to azithromycin and penicillin was different in all seven regions (p<0,05), the highest percentage of non-sensitive strains being found in Arequipa (63,6%), whereas the lowest percentage was found in Cusco (23.4%)., Conclusions: High levels of resistance found to penicillin, co-trimoxasole and macrolides in isolated pneumococcus strains of healthy carriers in all studied regions, and their association to a previous use of antibiotics, represent a significant public health problem in our country. This emphasizes the need to implement nationwide strategies to reduce the irrational use of antibiotics, especially among children. It is necessary to complement data of resistance to penicillin with the determination of minimal inhibitory concentration to make proper therapeutic recommendations.