Antibiotic resistance of urinary tract infection recurrences in a large U.S. integrated health care system.

BACKGROUND: Data on antibiotic resistance of uropathogens for UTI recurrences are lacking. METHODS: In a retrospective cohort of adults at Kaiser Permanente Southern California with culture-confirmed index uncomplicated UTI (uUTI) between 01/2016 and 12/2020, we examined the number and characteristics of subsequent culture-confirmed UTIs through 2021. RESULTS: We identified 148,994 individuals with a culture-confirmed index uUTI (88% female, 44% Hispanic, mean age 51 years [s.d. 19]), of whom 19% developed a subsequent culture-confirmed UTI after a median 300 days (IQR: 126-627). The proportion of UTI due to E. coli was highest for index uUTI (79%) and decreased to 73% for sixth UTI (UTI 6) (p-for trend <0.001), while the proportion due to Klebsiella spp increased from index UTI (7%) to UTI 6 (11%) (p-for-trend <0.001). Non-susceptibility to ≥1 and ≥3 antibiotic classes was observed in 57% and 13% of index uUTIs, respectively, and was higher for subsequent UTIs (65% and 20%, respectively, for UTI 6). Most commonly observed antibiotic non-susceptibility patterns included penicillins alone (12%), and penicillins, trimethoprim-sulfamethoxazole plus ≥1 additional antibiotic class (9%). CONCLUSIONS: Antibiotic non-susceptibility is common in UTIs and increases with subsequent UTIs. Continuous monitoring of UTI recurrences and susceptibility patterns are needed to guide treatment decisions.

Excess resource use and cost of drug-resistant infections for six key pathogens in Europe: a systematic review and Bayesian meta-analysis.

BACKGROUND: Quantifying the resource use and cost of antimicrobial resistance establishes the magnitude of the problem and drives action. OBJECTIVES: Assessment of resource use and cost associated with infections with six key drug-resistant pathogens in Europe. METHODS: A systematic review and Bayesian meta-analysis. DATA SOURCES: MEDLINE (Ovid), Embase (Ovid), Econlit databases, and grey literature for the period 1 January 1990, to 21 June 2022. STUDY ELIGIBILITY CRITERIA: Resource use and cost outcomes (including excess length of stay, overall costs, and other excess in or outpatient costs) were compared between patients with defined antibiotic-resistant infections caused by carbapenem-resistant (CR) Pseudomonas aeruginosa and Acinetobacter baumannii, CR or third-generation cephalosporin Escherichia coli (3GCREC) and Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant Enterococcus faecium, and patients with drug-susceptible or no infection. PARTICIPANTS: All patients diagnosed with drug-resistant bloodstream infections (BSIs). INTERVENTIONS: NA. ASSESSMENT OF RISK OF BIAS: An adapted version of the Joanna Briggs Institute assessment tool, incorporating case-control, cohort, and economic assessment frameworks. METHODS OF DATA SYNTHESIS: Hierarchical Bayesian meta-analyses were used to assess pathogen-specific resource use estimates. RESULTS: Of 5969 screened publications, 37 were included in the review. Data were sparse and heterogeneous. Most studies estimated the attributable burden by, comparing resistant and susceptible pathogens (32/37). Four studies analysed the excess cost of hospitalization attributable to 3GCREC BSIs, ranging from -€ 2465.50 to € 6402.81. Eight studies presented adjusted excess length of hospital stay estimates for methicillin-resistant S. aureus and 3GCREC BSIs (4 each) allowing for Bayesian hierarchical analysis, estimating means of 1.26 (95% credible interval [CrI], -0.72 to 4.17) and 1.78 (95% CrI, -0.02 to 3.38) days, respectively. CONCLUSIONS: Evidence on most cost and resource use outcomes and across most pathogen-resistance combinations was severely lacking. Given the importance of this evidence for rational policymaking, further research is urgently needed.

The Pitfalls of Abnormal Laboratory Value Interpretation in Vaccine Clinical Trials: The Example of Asymptomatic Transient Neutropenia.

Hematological and clinical chemistry measurements are an integral part of vaccine safety monitoring. While adopting a conservative approach is important to exclude potential risks for patients, the rationale and methodology underlying the assessment of given adverse events have to be well grounded to avoid raising unfounded concerns. Using asymptomatic transient neutropenia as an example, this paper aims to address the complexity of interpreting abnormal hematological values in vaccine clinical trials and to evaluate the validity of using neutrophil count cut-off points to assess neutropenia in the context of safety monitoring. The validity of the neutrophil count cut-off point methodology was assessed in terms of content validity (i.e., the extent to which a single neutrophil count below the cut-off point corresponds to a clinically significant adverse event), criterion validity (i.e., the extent to which a neutrophil count below a given cut-off point correlates with another manifestation of neutropenia, namely bacteremia), and construct validity (i.e., the exactness of the assumption that a neutrophil count below a given cut-off point corresponds to a reactogenic event caused by the vaccination). We argue that, because of within-individual physiological fluctuations, variations according to population demographics, and poor predictive potential with regard to neutropenia-associated infection, the application of the cut-off point methodology to neutropenia safety monitoring presents major limitations. Based on this assessment, we conclude that hematological laboratory values must be evaluated on a case-by-case basis by investigators to determine their clinical significance.

Safety of MenACWY-CRM vaccine exposure during pregnancy.

BACKGROUND: Although the meningococcal conjugate MenACWY-CRM vaccine is not approved for use in pregnant women, unintentional exposure during pregnancy can occur, especially during early pregnancy among women of child-bearing age. This study provides safety information about inadvertent MenACWY-CRM vaccination during pregnancy. METHODS: The evaluated population consisted of pregnant female members of Kaiser Permanente Southern California who inadvertently received MenACWY-CRM at 11-21 years of age during 09/30/2011-06/30/2013 within 28 days prior to conception or during pregnancy. Chart abstraction was conducted to identify pregnancy and birth outcomes, including spontaneous and induced abortions, preterm births, low weight births, and major congenital malformations (MCMs). RESULTS: There were 92 women who received MenACWY-CRM during the pregnancy exposure period, mainly during the first trimester (76.1%). Hispanics represented the largest race/ethnicity category (68.5%). Among the known pregnancy outcomes (n = 66; excluding induced abortions and unknown pregnancy outcomes), the prevalence of spontaneous abortions was 18.2% (n = 12). Among live born infants (n = 55; from 54 pregnancies), 14.5% (n = 8) were born preterm (<37 weeks gestation) and 9.1% (n = 5) had a low birthweight (<2500 g). The prevalence rate of MCMs among live born infants (n = 55) was 1.8% (n = 1). CONCLUSIONS: This study provides baseline prevalence estimates of spontaneous abortions, preterm births, low weight births, and MCMs among women inadvertently exposed to MenACWY-CRM during the pregnancy period. These estimates appear to be comparable with U.S. background prevalence estimates.

Incidence and economic burden of acute otitis media in children aged up to 5years in three Middle Eastern countries and Pakistan: A multinational, retrospective, observational study.

Epidemiological data on acute otitis media (AOM), an infectious disease frequently affecting children, are lacking in some countries. This study was undertaken to assess the incidence of AOM in children ≤5years in Saudi Arabia, Oman, Pakistan, and Turkey, as well as the economic burden from a parent/caregiver perspective. Medical records of 4043 children (Saudi Arabia=1023, Oman=998, Pakistan=1022, Turkey=1000) were retrospectively reviewed and the incidence of AOM episodes calculated from suspected and confirmed cases. Using a standardized Health Economics Questionnaire, parents recorded resource use and expenses incurred per AOM episode [in local currency and converted to US dollars (USD)]. The overall incidence of AOM episodes per 1000 person-years was: Saudi Arabia, 207 [95% confidence interval (CI): 178-238]; Oman, 105 (95% CI: 85-127); Pakistan, 138 (95% CI: 116-163); and Turkey, 99 (95% CI: 79-123). The mean total out-of-pocket healthcare expense incurred by parents/caregivers per episode was: Saudi Arabia USD67.1 [standard deviation (SD)=93.0], Oman USD16.1 (SD=16.4), Pakistan USD22.1 (SD=20.5), and Turkey USD33.6 (SD=44.9). The incidence of AOM episodes varied across all four countries, probably due to different diagnostic and management practices. Nevertheless, our results confirm that AOM causes a substantial burden to public health, reinforcing the need for cost-effective prevention strategies.

The variable clinicopathological categories and role of human papillomavirus in cervical adenocarcinoma: A hospital based nation-wide multi-center retrospective study across China.

We investigated HPV in adenocarcinoma presenting and managed as cervical adenocarcinoma (CADC) at seven major representative regional cancer centres across China. From 1,051 CADC cases diagnosed locally in 2005-2010, 881 had available paraffin embedded tissue. Initial review excluded 154 cases as other diagnoses or inappropriate specimens. In 718 eligible cases consensus panel pathology diagnosis was made using an algorithm incorporating p16 and progesterone receptor immunohistochemistry (IHC). Classification of cervical adenocarcinoma categories was subject to substantial pathological disagreement. High-risk human papillomaviruses (HR-HPV) DNA was studied by the sensitive SPF10 PCR-DEIA-LiPA25 version 1 for L1 genes and type-specific HR-HPV E6/7 gene PCR's. HR-HPV prevalence in whole tissue samples in eligible tested CADC was 74.5%: 100.0% in neuro-endocrine carcinoma (NEC), 82.2% in classical cervical adenocarcinoma (ADC-CX), 40.0% in adenocarcinoma-not otherwise specified (ADC-NOS) and 33.3% in endometrioid adenocarcinoma (ADC-ENDO). Higher mean age at diagnosis correlated with histological categories showing low HPV prevalence (Linear regression: ß= -13.794, p < 0.001). HPV-16 and 18 were associated with early development of CADC and a lower mean age correlated with carcinogenic risk of associated HPV (ß = -0.1829, p < 0.001). HPV-16 or HPV-18 was found in 88.2% of all HPV positive cases including multiple-infections. HPV-18 was the commonest HPV type in NEC (58.3%), ASC (40.2%) and ADC-CX (40.9%). The proportion of HPV-unrelated CADC and in different final histological categories varied geographically and by age. Although HPV negativity was predominantly associated with special categories of CADC, some HPV-negative usual adenocarcinomas indistinguishable by adjudicated microscopic diagnosis from ADC-CX were found and varied in frequency across China.

Epidemiology of community-acquired pneumonia and implications for vaccination of children living in developing and newly industrialized countries: A systematic literature review.

This systematic review evaluated the epidemiology of community-acquired pneumonia in children <6 y of age within 90 developing and newly industrialized countries. Literature searches (1990-2011), based on MEDLINE, EMBASE, Cochrane, CAB Global Health, WHO, UNICEF, country-specific websites, conferences, health-technology-assessment agencies, and the reference lists of included studies, yielded 8,734 records; 62 of 340 studies were included in this review. The highest incidence rate among included studies was 0.51 episodes/child-year, for children <5 y of age in Bangladesh. The highest prevalence was in Chinese children <6 months of age (37.88%). The main bacterial pathogens were Streptococcus pneumoniae, Haemophilus influenzae and Mycoplasma pneumoniae and the main viral pathogens were respiratory syncytial virus, adenovirus and rhinovirus. Community-acquired pneumonia remains associated with high rates of morbidity and mortality. Improved and efficient surveillance and documentation of the epidemiology and burden of community-acquired pneumonia across various geographical regions is warranted.

Epidemiology of otitis media in children from developing countries: A systematic review.

OBJECTIVE: This systematic review examined the epidemiology of otitis media (OM) in children <6 years within 90 developing and newly industrialised countries. METHODS: Literature searches (1992-2011), based on MEDLINE, EMBASE, WHO, Index Medicus, country-specific websites, conferences, and the reference lists of included studies, yielded 11,413 records; 59 of 344 studies analysed were included in this review. RESULTS: The majority of the identified studies provided only a single timepoint for OM. In children <6 years of age, OM prevalence was found to be 9.2% in Nigeria, 10% in Egypt, 6.7% in China, 9.2% in India, 9.1% in Iran and 5.1-7.8% in Russia. Few studies examined the etiology of OM and the antibacterial resistance. The most common bacterial pathogens were S. pneumoniae, H. influenzae and S. aureus. A high resistance to penicillin was reported in Nigeria and Turkey. CONCLUSIONS: Despite the variability between the identified studies, this review indicates that OM and its various sub-types remain a significant burden in different settings. However, the heterogeneity of studies and a general lack of reliable data made generalisation very difficult.

Human papillomavirus prevalence and type-distribution in women with cervical lesions: a cross-sectional study in Sri Lanka.

BACKGROUND: Cervical cancer ranks second among all cancers reported in Sri Lankan women. This study assessed the prevalence and type-distribution of human papillomavirus (HPV) among Sri Lankan women with invasive cervical cancer (ICC) and pre-cancerous lesions. METHODS: 114 women aged 21 years and above, hospitalized in the National Cancer Institute, Sri Lanka with a diagnosis of ICC or cervical intraepithelial neoplasia (CIN) 2/3 were prospectively enrolled between October 2009 and September 2010 (110430/NCT01221987). The cervical biopsy or excision specimens collected during routine clinical procedures were subjected to histopathological review. DNA was extracted from samples with a confirmed histological diagnosis and was amplified using polymerase chain reaction and HPV DNA was detected using Enzyme Immuno Assay. HPV positive samples were typed using reverse hybridization Line Probe Assay. RESULTS: Of the cervical samples collected, 93.0% (106/114) had a histologically confirmed diagnosis of either ICC (98/106) or CIN 2/3 (8/106). Among all ICC cases, squamous cell carcinoma was diagnosed in the majority of women (81.6% [80/98]). HPV prevalence among ICC cases was 84.7% (83/98). The HPV types most commonly detected in ICC cases with single HPV infection (98.8% [82/83]) were HPV-16 (67.3%) and HPV-18 (9.2%). Infection with multiple HPV types was recorded in a single case (co-infection of HPV-16 and HPV-59). CONCLUSIONS: HPV was prevalent in most women with ICC in Sri Lanka; HPV-16 and HPV-18 were the predominantly detected HPV types. An effective prophylactic vaccine against the most prevalent HPV types may help to reduce the burden of ICC disease.

Epidemiological features of Human Papillomavirus (HPV) infection among women living in Mainland China.

Cancer of the cervix is the third most common cancer in women worldwide, more than 85% of the cases occurring in developing countries such as China. In China, since a national cancer registry is already set up but with geographically limited data generated, the burden of cervical cancer is believed to be underestimated. High- risk human papillomavirus (HR-HPV) prevalence among women attending routine cervical cancer screening programs has been shown to correlate well with cervical cancer incidence rates based on independently obtained HPV prevalence data as well as findings for the worldwide cervical cancer burden. Therefore, reviewing data on HR-HPV prevalence in population-based screening studies and hospital-based case studies will be important in the context of better understanding the cervical cancer burden and for the evaluation of the potential impact of HPV vaccination in the country. With the advent of prophylactic vaccines, significant progress is likely to be made in cervical cancer prevention. This article reviews available data on the HPV epidemiology over a 12-year time period (2001-2012) in mainland China under different epidemiological aspects: by age group of study population, by ethnicity, by geographic area, as well as time period. The authors also review the potential acceptability of HPV vaccination among Chinese women.

A multi-center survey of age of sexual debut and sexual behavior in Chinese women: suggestions for optimal age of human papillomavirus vaccination in China.

OBJECTIVE: Cervical cancer is the second most common cancer among women worldwide, and over 85% of cervical cancers occur in developing countries such as China. Lack of resources for nationwide cervical cancer screening in China makes vaccination against oncogenic strains of HPV particularly important. Knowledge of age at sexual debut and sexual behavior is essential prior to implementation of a national vaccination program. METHODS AND MATERIALS: A cross-sectional epidemiologic survey was conducted across 21 urban and rural sites in China to assess age at sexual debut and sexual behavior. 98.6% of the 11,852 recruited women aged 15-59 years were included in the analysis. Data were collected using a short, nurse-administered questionnaire and analyzed using standard descriptive statistics and survival analysis. RESULTS: In urban areas, more than ten percent of the 15-19 year old age group were already sexually active at the time of interview; this number increased to nearly 44% in the 20-24 year old age group. Chinese young women with an occupation were more likely to be sexually active compared to female students of the same age, irrespective of area of residence. The crude median sexual debut age for the youngest age group was 17 years, earlier than the sexual debut age reported by older cohorts. Younger age cohorts had an earlier menarche age than older cohorts and were more likely to have more sexual partners than older women, and more likely to have partners with more than one female partner. CONCLUSION: There is a trend towards earlier sexual debut and riskier sexual behaviors in younger age groups of Chinese women. These findings suggest that HPV vaccination of women between the ages of 13 and 15 years, before the completion of national compulsory education, is likely to contribute to the prevention of HPV infection and cervical cancer in China.

Human papillomavirus type-distribution in cervical cancer in China: the importance of HPV 16 and 18.

Prophylactic vaccination against HPV 16 and 18 has the potential for effective prevention of high-grade precancer (cervical intraepithelial neoplasia [CIN)] 2/3) and ICC caused by these viruses (globally 50 and 70%, respectively) when employed in women prior to starting sexual activity. To provide data for decisions on HPV vaccination in China, we determined HPV type-distribution in ICC and CIN 2/3 from women of different regions within China. A multicenter study was conducted by randomized sampling of paraffin blocks of 664 ICC (630 squamous cell carcinoma [SCC]; 34 adenocarcinoma [ADC]), 569 CIN 2/3 cases from seven regions of China. Histological diagnosis was confirmed in 1,233 cases by consensus review. HPV DNA was detected using the SPF10 LiPA25 version 1 assay. HPV prevalence was 97.6% in SCC, 85.3% in adenocarcinoma, and 98.9% in CIN 2/3. HPV 16 (76.7%) and HPV 18 (7.8%) were the most common, together accounting for 84.5% of SCC, followed by HPV 31 (3.2%), HPV 52 (2.2%), and HPV 58 (2.2%). HPV positivity in SCC did not differ notably by region. However, SCC cases from women