Pregnancy outcomes for women with pre-existing renal disease and the role of a dedicated joint maternal medicine and renal clinic: A retrospective cohort study.

OBJECTIVE: To reaffirm the value of a joint obstetric and renal clinic on obstetric outcomes in patients with high-risk pregnancies due to chronic kidney disease (CKD). METHODS: This was a retrospective cohort study of patients who attended the clinic between 2005 and December 2021. The hospital is a regional tertiary unit for renal medicine and a maternal medicine hub. The data included all women with pre-existing renal conditions who were cared for in a dedicated renal and obstetric clinic. Datasets were extracted from hospital notes, the renal database, clinical data and maternity electronic health records. The data analyzed included pre-existing renal conditions, biochemical parameters related to the renal condition, pregnancy outcomes included miscarriages, gestation, mode of delivery, postpartum hemorrhage (PPH), loss, birth weight and neonatal admission. RESULTS: The results were as follows: Lupus nephritis: four term deliveries; three had pre-eclampsia; two PPH and two miscarriages. Four estimated glomerular filtration rates (eGFRs) returned to baseline levels within 12 months. With regard to IgA nephropathy there were five live births, four term deliveries, two pre-eclampsia (PE) and five cesarean sections (CS). All eGFRs returned to baseline within 12 months. With regard to patients with adult polycystic kidney disease (APKD), there were six live births, two had pre-eclampsia and there were five term vaginal deliveries. CONCLUSION: Patients with lupus nephritis, APKD, and IgA demonstrated a higher incidence of adverse pregnancy outcomes as compared with our local pregnant population. Our findings reflect those of larger studies and support the role of combined renal/obstetric clinics. More research and larger scale studies are needed into specific CKD conditions and their outcomes.

Epidemiology of Salmonella enterica subspecies enterica serotypes, isolated from imported, farmed and feral poultry in the Cayman Islands.

Non-typhoidal Salmonellae (NTS) are common foodborne pathogens throughout the world causing acute gastroenteritis. Compared to North America and Europe, there is little information on NTS in the Caribbean. Here we investigated the prevalence and characteristics of NTS present in the local poultry of the Cayman Islands to determine the public health risk. In total, we collected 156 samples. These were made up of boot swabs of 31 broiler farms and 31 layer farms (62 samples), paper bedding from 45 imported chick boxes, and 49 pooled cecum samples from feral chickens, each sample representing 10 individual chickens. Salmonella was isolated using the ISO 6579 protocol and isolates were characterized using Whole Genome Sequencing (WGS) analysis. Eighteen Salmonella isolates were obtained and comprised six S. enterica subspecies enterica serotypes and one subspecies houtenae serotype. Serotypes were: S. Kentucky (n = 9), S. Saintpaul (n = 5), S. Javiana (n = 1), S. Senftenberg (n = 1), S. Poona (n = 1) and S. Agona (n = 1). S. Kentucky strains were all ST152 and clonally related to poultry strains from the United states. S. Saintpaul ST50 strains showed clonality to North American strains. Over half of the strains (n = 11) contained resistance genes to at least two antibiotic groups and five strains were MDR, mainly those from imported day-old chicks. The blaCMY-2 gene was found in S. Kentucky from day-old chicks. Strains from feral poultry had no acquired AMR genes. While serotypes from feral poultry have been identified in human infections, they pose minimal risk due to their low virulence.

Reducing laboratory costs through rational testing in suspected pre-eclampsia.

The current electronic laboratory order set at Epsom and St Helier University Hospitals NHS Trust for suspected pre-eclampsia includes a full blood count, urea and electrolytes, liver function, gamma-glutamyltransferase and uric acid. Local and national guidelines do not recommend the use of gamma-glutamyltransferase or uric acid for the investigation or monitoring of pre-eclampsia, as they are poor predictors of maternal and neonatal outcomes. We aimed to remove the automatic inclusion of gamma-glutamyltransferase and uric acid from the electronic laboratory order set for suspected pre-eclampsia. Stakeholders were approached to gain an understanding of whether gamma-glutamyltransferase and uric acid were being used in the clinical assessment of suspected pre-eclampsia. Obstetric consultants and maternity staff confirmed that they do not use uric acid in their clinical assessment, despite the laboratory phoning with abnormal results. In addition, an isolated gamma-glutamyltransferase rise is of no particular significance and is not part of the National Institute for Health and Care Excellence (NICE) diagnostic criteria for pre-eclampsia. The baseline number of gamma-glutamyltransferase and uric acid requests from the maternity department was identified over 2 months. The hospital information technology service was then asked to remove gamma-glutamyltransferase and uric acid from the electronic laboratory order set. The number of gamma-glutamyltransferase and uric acid requests from the maternity department following the intervention was identified over 2 months. A significant reduction in both gamma-glutamyltransferase and uric acid requests were noted. In addition, the midwives within the maternity assessment unit noted a significant reduction in phone calls from the laboratory to escalate abnormal blood results. This has saved the trust money and reduced staff time answering phone calls regarding abnormal blood results. A repeat assessment at 8 months following the removal of gamma-glutamyltransferase and uric acid demonstrated sustainability of the project.

Mapping Protective Regions on a Three-Dimensional Model of the Moraxella catarrhalis Vaccine Antigen Oligopeptide Permease A.

A vaccine against Moraxella catarrhalis would reduce tremendous morbidity, mortality, and financial burden by preventing otitis media in children and exacerbations of chronic obstructive pulmonary disease (COPD) in adults. Oligopeptide permease A (OppA) is a candidate vaccine antigen that is (i) a nutritional virulence factor expressed on the bacterial cell surface during infection, (ii) widely conserved among strains, (iii) highly immunogenic, and (iv) a protective antigen based on its capacity to induce protective responses in immunized animals. In the present study, we show that the antibodies to OppA following vaccination mediate accelerated clearance in animals after pulmonary challenge. To identify regions of OppA that bind protective antibodies, truncated constructs of OppA were engineered and studied to map regions of OppA with surface-accessible epitopes that bind high-avidity antibodies following vaccination. Protective epitopes were located in the N and C termini of the protein. Immunization of mice with constructs corresponding to these regions (T5 and T8) induced protective responses. Studies of overlapping peptide libraries of constructs T5 and T8 with OppA immune serum identified two discrete regions on each construct. These potentially protective regions were mapped on a three-dimensional computational model of OppA, where regions with solvent-accessible amino acids were identified as three potentially protective epitopes. In all, these studies revealed two regions with three specific epitopes in OppA that induce potentially protective antibody responses following vaccination. Detection of antibodies to these regions could serve to guide vaccine formulation and as a diagnostic tool for monitoring development of protective responses during clinical trials.

Association between insulin resistance and preeclampsia in obese non-diabetic women receiving metformin.

OBJECTIVES: To examine whether the reduced incidence of preeclampsia in non-diabetic obese pregnant women treated with metformin is mediated by changes in insulin resistance. METHODS: This was a secondary analysis of obese pregnant women in a randomised trial (MOP trial). Fasting plasma glucose and insulin were measured in 384 of the 400 women who participated in the MOP trial. Homeostasis model assessment of insulin resistance (HOMA-IR) was compared in the metformin and placebo groups and in those that developed preeclampsia versus those that did not develop preeclampsia. RESULTS: At 28 weeks, median HOMA-IR was significantly lower in the metformin group. Logistic regression analysis demonstrated that there was a significant contribution in the prediction of preeclampsia from maternal history of chronic hypertension and gestational weight gain, but not HOMA-IR either at randomisation (p = 0.514) or at 28 weeks (p = 0.643). CONCLUSIONS: Reduced incidence of preeclampsia in non-diabetic obese pregnant women treated with metformin is unlikely to be due to changes in insulin resistance.

A Cation-Binding Surface Protein as a Vaccine Antigen To Prevent Moraxella catarrhalis Otitis Media and Infections in Chronic Obstructive Pulmonary Disease.

Moraxella catarrhalis is an exclusively human respiratory tract pathogen that is a common cause of otitis media in children and respiratory tract infections in adults with chronic obstructive pulmonary disease. A vaccine to prevent these infections would have a major impact on reducing the substantial global morbidity and mortality in these populations. Through a genome mining approach, we identified AfeA, an ∼32-kDa substrate binding protein of an ABC transport system, as an excellent candidate vaccine antigen. Recombinant AfeA was expressed and purified and binds ferric, ferrous, manganese, and zinc ions, as demonstrated by thermal shift assays. It is a highly conserved protein that is present in all strains of M. catarrhalis Immunization with recombinant purified AfeA induces high-titer antibodies that recognize the native M. catarrhalis protein. AfeA expresses abundant epitopes on the bacterial surface and induces protective responses in the mouse pulmonary clearance model following aerosol challenge with M. catarrhalis Finally, AfeA is expressed during human respiratory tract infection of adults with chronic obstructive pulmonary disease (COPD). Based on these observations, AfeA is an excellent vaccine antigen to be included in a vaccine to prevent infections caused by M. catarrhalis.

ATP-Binding Cassette (ABC) Transporters of the Human Respiratory Tract Pathogen, Moraxella catarrhalis: Role in Virulence.

Moraxella catarrhalis is a human respiratory tract pathogen that causes otitis media (middle ear infections) in children and respiratory tract infections in adults with chronic obstructive pulmonary disease. In view of the huge global burden of disease caused by M. catarrhalis, the development of vaccines to prevent these infections and better approaches to treatment have become priorities. In previous work, we used a genome mining approach that identified three substrate binding proteins (SBPs) of ATP-binding cassette (ABC) transporters as promising candidate vaccine antigens. In the present study, we performed a comprehensive assessment of 19 SBPs of 15 ABC transporter systems in the M. catarrhalis genome by engineering knockout mutants and studying their role in assays that assess mechanisms of infection. The capacity of M. catarrhalis to survive and grow in the nutrient-limited and hostile environment of the human respiratory tract, including intracellular growth, account in part for its virulence. The results show that ABC transporters that mediate uptake of peptides, amino acids, cations and anions play important roles in pathogenesis by enabling M. catarrhalis to 1) grow in nutrient-limited conditions, 2) invade and survive in human respiratory epithelial cells and 3) persist in the lungs in a murine pulmonary clearance model. The knockout mutants of SBPs and ABC transporters showed different patterns of activity in the assay systems, supporting the conclusion that different SBPs and ABC transporters function at different stages in the pathogenesis of infection. These results indicate that ABC transporters are nutritional virulence factors, functioning to enable the survival of M catarrhalis in the diverse microenvironments of the respiratory tract. Based on the role of ABC transporters as virulence factors of M. catarrhalis, these molecules represent potential drug targets to eradicate the organism from the human respiratory tract.

Spontaneous pregnancies following discontinuation of IVF/ICSI treatment: an internet-based survey.

The objective was to determine the likelihood of conceiving spontaneously following cessation of IVF/ICSI; how long does it take and what factors are associated with conception? The design was an internet-based survey. All registered users of www.ivf-infertility.com received an electronic questionnaire addressing issues relating to the duration and cause of infertility, number of IVF/ICSI cycles and outcome, whether they conceived following cessation of IVF/ICSI and the time taken to conceive and outcome. Four hundred and eighty four patients responded of whom 403 met the study criteria. The overall cumulative live birth rate over a 6-year period following cessation of IVF/ICSI was 29%. Eighty-two percent of conceptions occurred within 2 years. Positive factors associated with spontaneous conception were unexplained infertility (p = 0.02), ovulation dysfunction (p = 0.01), infertility less than four years prior to IVF/ICSI (p = 0.045) and 2 years or less since discontinuation of IVF/ICSI (p < 0.001) and up to four attempts at IVF/ICSI (p = 0.02). In conclusion, 29% of couples conceived spontaneously over a 6-year period following the cessation of IVF/ICSI. The findings of this study can be used to counsel and reassure women following IVF/ICSI.

Sulfate-binding protein, CysP, is a candidate vaccine antigen of Moraxella catarrhalis.

Moraxella catarrhalis causes otitis media in children and respiratory tract infections in adults with chronic obstructive pulmonary disease (COPD). A vaccine to prevent M. catarrhalis infections would have an enormous impact globally in preventing morbidity caused by M. catarrhalis in these populations. Using a genome mining approach we have identified a sulfate binding protein, CysP, of an ATP binding cassette (ABC) transporter system as a novel candidate vaccine antigen. CysP expresses epitopes on the bacterial surface and is highly conserved among strains. Immunization with CysP induces potentially protective immune responses in a murine pulmonary clearance model. In view of these features that indicate CysP is a promising vaccine antigen, we conducted further studies to elucidate its function. These studies demonstrated that CysP binds sulfate and thiosulfate ions, plays a nutritional role for the organism and functions in intracellular survival of M. catarrhalis in human respiratory epithelial cells. The observations that CysP has features of a vaccine antigen and also plays an important role in growth and survival of the organism indicate that CysP is an excellent candidate vaccine antigen to prevent M. catarrhalis otitis media and infections in adults with COPD.

Role of the oligopeptide permease ABC Transporter of Moraxella catarrhalis in nutrient acquisition and persistence in the respiratory tract.

Moraxella catarrhalis is a strict human pathogen that causes otitis media in children and exacerbations of chronic obstructive pulmonary disease in adults, resulting in significant worldwide morbidity and mortality. M. catarrhalis has a growth requirement for arginine; thus, acquiring arginine is important for fitness and survival. M. catarrhalis has a putative oligopeptide permease ABC transport operon (opp) consisting of five genes (oppB, oppC, oppD, oppF, and oppA), encoding two permeases, two ATPases, and a substrate binding protein. Thermal shift assays showed that the purified recombinant substrate binding protein OppA binds to peptides 3 to 16 amino acid residues in length regardless of the amino acid composition. A mutant in which the oppBCDFA gene cluster is knocked out showed impaired growth in minimal medium where the only source of arginine came from a peptide 5 to 10 amino acid residues in length. Whether methylated arginine supports growth of M. catarrhalis is important in understanding fitness in the respiratory tract because methylated arginine is abundant in host tissues. No growth of wild-type M. catarrhalis was observed in minimal medium in which arginine was present only in methylated form, indicating that the bacterium requires l-arginine. An oppA knockout mutant showed marked impairment in its capacity to persist in the respiratory tract compared to the wild type in a mouse pulmonary clearance model. We conclude that the Opp system mediates both uptake of peptides and fitness in the respiratory tract.

Substrate binding protein SBP2 of a putative ABC transporter as a novel vaccine antigen of Moraxella catarrhalis.

Moraxella catarrhalis is a common respiratory tract pathogen that causes otitis media in children and infections in adults with chronic obstructive pulmonary disease. Since the introduction of the pneumococcal conjugate vaccines with/without protein D of nontypeable Haemophilus influenzae, M. catarrhalis has become a high-priority pathogen in otitis media. For the development of antibacterial vaccines and therapies, substrate binding proteins of ATP-binding cassette transporters are important targets. In this study, we identified and characterized a substrate binding protein, SBP2, of M. catarrhalis. Among 30 clinical isolates tested, the sbp2 gene sequence was highly conserved. In 2 different analyses (whole-cell enzyme-linked immunosorbent assay and flow cytometry), polyclonal antibodies raised to recombinant SBP2 demonstrated that SBP2 expresses epitopes on the bacterial surface of the wild type but not the sbp2 mutant. Mice immunized with recombinant SBP2 showed significantly enhanced clearance of M. catarrhalis from the lung compared to that in the control group at both 25-µg and 50-µg doses (P < 0.001). We conclude that SBP2 is a novel, attractive candidate as a vaccine antigen against M. catarrhalis.

The importance of visceral fat mass in obese pregnant women and relation with pregnancy outcomes.

BACKGROUND: Maternal obesity is a well established risk factor for gestational diabetes but it is not known if the pattern of maternal fat distribution predicts adverse pregnancy outcomes. METHODS: Body composition was assessed by bioimpedance using Inbody 720® in 302 consecutive obese pregnant women attending a weight management clinic. The relation of visceral fat mass and total percentage body fat with the development of gestational diabetes and perinatal outcomes was evaluated. RESULTS: Women developing gestational diabetes (Group 1; n = 72) were older, had higher body mass indices and greater central obesity (waist:hip ratio, visceral fat mass) compared with those remaining normoglycaemic. Visceral fat mass, but not percentage body fat, correlated with fasting glucose in all patients (r = 0.2, p < 0.001) and particularly those in Group 1 (r = 0.35, p = 0.002). Visceral fat mass, but not percentage body fat, also correlated strongly with glycaemia, particularly in Group 1 (r = 0.47, p < 0.0001). Visceral fat mass also showed a weak but significant correlation with baby weight (r = 0.17, p = 0.01). DISCUSSION: Central obesity, as assessed by early pregnancy waist:hip ratio and particularly by visceral fat mass, is a predictor of gestational diabetes in addition to classical risk factors and may help identify those obese patients at increased risk of complications.

Immigration, Work, and Health: A Literature Review of Immigration Between Mexico and the United States.

Understanding the influence someone's job or career has on their health goes beyond the physical, emotional and social hazards, risks and conditions that they face at work. One's job or career also exerts a significant influence over other aspects of life that contribute or detract from their health and that of their family. Work is the major incentive for Latin American migration to the United States. Latino immigrants experience increasingly poorer outcomes for physical health and chronic diseases the longer they remain in the U.S. The strong link between work and immigration suggests that, for many Latin Americans, immigration can be understood as a career path which puts them, and their family members, in situations that can change their physical, emotional, and social health as a condition of their employment. Given the large number of Latin Americans who emigrate for work, it is essential that the unique physical, mental and social impacts of emigration are accounted for when working with clients impacted by emigration at the individual, family and community level as well as those social workers practicing at the system level. This paper is a literature review that explores the impact that emigrating for work has on the health of those that emigrate and their family members that stay behind.

Role of the zinc uptake ABC transporter of Moraxella catarrhalis in persistence in the respiratory tract.

Moraxella catarrhalis is a human respiratory tract pathogen that causes otitis media in children and lower respiratory tract infections in adults with chronic obstructive pulmonary disease. We have identified and characterized a zinc uptake ABC transporter that is present in all strains of M. catarrhalis tested. A mutant in which the znu gene cluster is knocked out shows markedly impaired growth compared to the wild type in medium that contains trace zinc; growth is restored to wild-type levels by supplementing medium with zinc but not with other divalent cations. Thermal-shift assays showed that the purified recombinant substrate binding protein ZnuA binds zinc but does not bind other divalent cations. Invasion assays with human respiratory epithelial cells demonstrated that the zinc ABC transporter of M. catarrhalis is critical for invasion of respiratory epithelial cells, an observation that is especially relevant because an intracellular reservoir of M. catarrhalis is present in the human respiratory tract and this reservoir is important for persistence. The znu knockout mutant showed marked impairment in its capacity to persist in the respiratory tract compared to the wild type in a mouse pulmonary clearance model. We conclude that the zinc uptake ABC transporter mediates uptake of zinc in environments with very low zinc concentrations and is critical for full virulence of M. catarrhalis in the respiratory tract in facilitating intracellular invasion of epithelial cells and persistence in the respiratory tract.

Development and implementation of Baltimore Healthy Eating Zones: a youth-targeted intervention to improve the urban food environment.

Poor accessibility to affordable healthy foods is associated with higher rates of obesity and diet-related chronic diseases. We present our process evaluation of a youth-targeted environmental intervention (Baltimore Healthy Eating Zones) that aimed to increase the availability of healthy foods and promote these foods through signage, taste tests and other interactive activities in low-income Baltimore City. Trained peer educators reinforced program messages. Dose, fidelity and reach-as measured by food stocking, posting of print materials, distribution of giveaways and number of interactions with community members-were collected in six recreation centers and 21 nearby corner stores and carryouts. Participating stores stocked promoted foods and promotional print materials with moderate fidelity. Interactive sessions were implemented with high reach and dose among both adults and youth aged 10-14 years, with more than 4000 interactions. Recreation centers appear to be a promising location to interact with low-income youth and reinforce exposure to messages.

Microalbuminuria in HIV disease.

BACKGROUND/AIMS: Microalbuminuria is a marker for early kidney disease and cardiovascular risk. The purposes of this study were to determine the prevalence of microalbuminuria in an HIV-infected clinic population, to test the predictive value of a single urine albumin/creatinine ratio (ACR) to identify persistent microalbuminuria and to examine covariates of microalbuminuria. METHODS: We conducted a prospective cohort study of HIV-infected subjects (n = 182) without proteinuria (urine protein/creatinine ratio ≥0.5 g/g), elevated serum creatinine, diabetes, or chronic inflammatory conditions. Subjects completed three research visits within 9 months. Microalbuminuria was defined as the geometric mean ACR of 25-355 mg/g for females and 17-250 mg/g for males. RESULTS: The prevalence of microalbuminuria was 14%. The negative predictive value of a single urine ACR determination was 98%, whereas the positive predictive value was only 74%. Microalbuminuria was similar among Black (15%) and non-Black (14%) subjects (p = 0.8). Subjects with microalbuminuria were more likely to have hypertension (p = 0.02) and metabolic syndrome (p = 0.03). While duration of HIV infection and the level of HIV viremia were similar between groups, those with microalbuminuria were more likely to have a CD4 count <200 cells/µl (p = 0.0003). In a multivariate logistic regression analysis, the only significant independent predictors of microalbuminuria were low CD4 count (p = 0.018) and current ritonavir exposure (p = 0.04). CONCLUSION: The prevalence of microalbuminuria in an HIV-infected clinic population was similar to earlier reports, and was associated with hypertension and impaired immune function. A single normal ACR determination effectively excludes microalbuminuria, whereas an elevated ACR requires confirmation.

Pregnancy outcomes after metformin treatment for gestational diabetes: a case-control study.

BACKGROUND: There is increasing evidence that metformin is safe and effective in the treatment of gestational diabetes (GDM), although it has not yet been widely accepted for routine practice. We compared pregnancy outcomes in women with gestational GDM treated with metformin or dietary measures alone. METHODS: Women with GDM (324) not adequately controlled by diet received metformin according to protocol based on their home glucose results. Pregnancy outcomes in these women were compared with 175 GDM women treated with diet alone and matched for age and ethnicity. RESULTS: The percentage of macrosomic babies (birth weight [BW] centile >90th centile) and small for gestational age (SGA) (BW <10th centile) in the metformin group was significantly reduced compared with the diet group (12.7% versus 20%; P < 0.05 [macrosomia]; 7.7% versus 14.3% [SGA] P < 0.05). CONCLUSIONS: Metformin treatment had a favourable impact on the rates of macrosomia and SGA despite more severe glucose intolerance at baseline.

Infertility treatment: when is it time to give up? An Internet-based survey.

INTRODUCTION: Many factors have been suggested that influence a couple's decision to stop infertility treatment despite not achieving their goal of having a baby. This Internet-based questionnaire study aims to shed light on these reasons by surveying patients who have received treatment from a variety of different centres. METHODS: Registered users of an independent infertility website were invited to participate in the survey by filling in a structured questionnaire. RESULTS: Eighty users completed the questionnaire. Fifty-eight percent of patients received treatment in just one centre. Seventy-eight percent of the patients paid for the treatment themselves. Forty-two percent of couples intended to have only one treatment cycle and 60% of couples reported undergoing more cycles than they had originally intended. Ten percent of patients regretted not stopping their treatment earlier. The most common reasons why patients opted against further treatment cycles were financial constraints (46%), emotional burden (35%), poor response to treatment (29%) and poor egg quality (19%). CONCLUSIONS: The decision to stop treatment despite poor outcomes is a difficult one and unique to the couple. The findings of this study are consistent with the widely held belief that in vitro fertilization is a stressful, expensive process, given that almost all women cited these as reasons to stop treatment.

Characterization and evaluation of the Moraxella catarrhalis oligopeptide permease A as a mucosal vaccine antigen.

Moraxella catarrhalis is a common cause of otitis media in children and of lower respiratory tract infections in adults with chronic obstructive pulmonary disease; therefore, these two groups would benefit from a vaccine to prevent M. catarrhalis infections. A genome mining approach for vaccine antigens identified oligopeptide permease protein A (OppA), an oligopeptide binding protein of an apparent oligopeptide transport system. Analysis of the oppA gene by PCR and sequence analysis revealed that OppA is highly conserved among clinical isolates of M. catarrhalis. Recombinant OppA was expressed as a lipoprotein and purified, and an oppA knockout mutant was constructed. Antiserum raised to recombinant purified OppA recognized epitopes on the bacterial surface of the wild type but not the OppA knockout mutant. Antibodies raised to purified recombinant OppA recognized native OppA in multiple strains. Intranasal immunization of mice induced systemic and mucosal antibodies to OppA and resulted in enhanced clearance of M. catarrhalis in a mouse pulmonary clearance model. OppA is a highly conserved, immunogenic protein that expresses epitopes on the bacterial surface and that induces potentially protective immune responses in a mouse model. OppA should be evaluated further as a vaccine antigen for M. catarrhalis.

Antibiotic resistance in sputum isolates of Streptococcus pneumoniae in chronic obstructive pulmonary disease is related to antibiotic exposure.

Streptococcus pneumoniae (S. pneumoniae) is recovered from sputum of patients with chronic obstructive pulmonary disease (COPD) during stable disease and exacerbations. In patients with community acquired pneumonia, antibiotic exposure in the prior 3-6 months is associated with recovery of antibiotic resistant isolates of S. pneumoniae. Whether the same relationship is seen in COPD is not known. From April 1994 to June 2004, 127 adults with COPD were enrolled in a prospective longitudinal study. Sputum isolates of S. pneumoniae were characterized with susceptibility testing and pulsed-field gel electrophoresis (PFGE). The relationship between antibiotic use in the previous 3 and 6 months with either new acquisition of a resistant pneumococcal isolate or development of resistance (4-fold increase in MIC) in a pre-existing colonizing pneumococcal strain was determined. A total of 194 pneumococcal isolates were recovered from 38 patients. Among 71 newly acquired and 4 resistance-emergent strains analyzed further, rates of resistance to penicillin (MIC ≥2), erythromycin (MIC ≥1), tetracycline (MIC ≥8) and trimethoprim/sulfamethoxazole (MIC ≥4) were 8%, 24%, 17% and 16% respectively. Flouroquinolone resistance was not seen. Among strains isolated from patients exposed to a macrolide within 6 months, 53.6% displayed erythromycin resistance vs. 14% of strains without such exposure (p = 0.00085). Similar associations were not seen for other antibiotics. Macrolide use in the previous 6 months is associated with macrolide resistance in sputum isolates of S. pneumoniae. Recent antibiotic exposure may help in determining appropriate antibiotic treatment in these patients.