Comorbid Infections Research Articles

Characteristics of Primary Thrombotic Microangiopathy in Patients with and without Human Immunodeficiency Virus: Thirteen Year Experience at the University of Maryland

Background: Thrombotic microangiopathy (TMA) is a syndrome characterized by thrombocytopenia and microangiopathic hemolytic anemia. TMAs can be primary or secondary to variety of clinical conditions: pregnancy, malignancy, autoimmune diseases and medications. Human immunodeficiency virus (HIV) infection is associated with thrombotic thrombocytopenic purpura (TTP), although the pathophysiology and clinical presentation has not been well-defined.Methods: In an urban center with a 3% prevalence of HIV infection, we retrospectively reviewed the charts of patients who underwent therapeutic plasma exchange (TPE) for TTP from January 2000 to December 2013 after IRB approval. The aim of our study is to describe and analyze the clinical differences seen in primary TMA with or without HIV infection. Differences of laboratory data between the 2 groups were assessed using the t -test.Results: Of 188 patients requiring TPE over 13 years at our urban tertiary medical center, 31 (17%) were HIV-positive and 154 (83%) were HIV negative. HIV-positive patients had median age of 43 years (range, 26-65), 30 (96%) black, 23 (74%) female, 23 (74%) with primary TMA. HIV-negative patients had a median age of 46 years (range, 16-82) 92 (59%) black and 104 (66%) female, 54 (35%) with primary TMA. Fifteen of 31 HIV-positive patients (48%) presented with comorbid infections caused by bacterial, viral, fungal and opportunistic organisms, whereas only 29 of the 157 (18%) HIV-negative patients presented with concomitant infection.The following comparisons were made between HIV-positive (n=23) and negative (n=54) patients with primary TMA. Laboratory data revealed that hemoglobin was lower (mean Hb: 7.0 vs 8.1 g/dL, P=0.03) and renal failure was more severe (mean creatinine 2.3 vs 1.6, P=0.04) in HIV-positive patients compared with HIV-negative. There was no statistically difference between 2 groups in LDH and platelet counts. ADAMTS13 level was available in 6/23 HIV positive and 18/54 HIV-negative primary TMA patients. The level <10% was seen in 11 HIV-negative patients. ADAMTS13 level of HIV-positive patients ranged from 14 to 74 (Sample collection was delayed in 3/6 patients). All HIV-positive cases showed immunosuppression, with a mean CD4 count of 124 cells/ µL, ranging from 2 to 444 cells/ µL. Regarding treatment, HIV-negative patients required an average of 23% more TPE sessions (18 vs. 15) than HIV-positive patients. Steroids, intravenous immune gamma-globulin and rituximab were used in both groups. Mortality and complications were similar in both groups.Discussion: The frequency of 1 in 5 patients with TMA also having HIV at the University of Maryland is one of the highest frequencies reported in the literature outside of South Africa. Our study suggests that HIV-positive patients might have a thrombotic microangiopathy triggered by an infection more commonly than patients without HIV. The absence of ADAMTS13 deficiency was notable in our HIV-positive patients. However, delayed sample collection in 3/6 patients might limit the significance of this data. The etiology of TMA in HIV infection remains unclear. Prior studies have suggested that a HIV-specific mechanism such as B cell dysregulation as a result of T cell depletion; cytokine production and HIV infection of endothelial cells play a role. The limited number of patients seen individual centers precludes controlled clinical trials to study the efficacy of treatment for this serious disease. Future prospective collaborative research studies are needed to expand our knowledge of TMA in HIV-positive populations. DisclosuresNo relevant conflicts of interest to declare.

Comorbid infections in patients with rheumatoid arthritis

The problem of comorbid infections (CI) in modern rheumatology remains important. The reasons behind it include the presence of an autoimmune rheumatic disease and the need to use immunosuppressant drugs. We discuss some problems of CI under EULAR recommendations (2013) for the management of rheumatoid arthritis (RA). The incidence rates of comorbid infections in patients treated with different disease- modifying anti-rheumatic and biological drugs are analyzed. The significance of measures for preventing CI in management of RA patients is demonstrated. The significance of vaccination (first of all, with anti-influenza and pneumococcal vaccines) of RA patients to reduce the incidence rate of lower respiratory tract infections and the risk of infection-related mortality is emphasized. Vaccination is recommended even if suboptimal outcome is expected.

Co-Morbid Infections in Hansen's Disease Patients in the United States: Considerations for Treatment

120 patients attending a Hansen's disease public health satellite clinic were evaluated for selected latent co-morbidities, consisting of strongyloidiasis, Chagas disease, hepatitis B, HIV, and tuberculosis, and potential exacerbation by immunosuppressive therapy. Implications for treatment of Hansen's disease are discussed.

Relevance of lipopolysaccharide levels in HIV-associated neurocognitive impairment: the Neuradapt study

Contributory factors to HIV-associated neurocognitive disorders (HAND) have been shown to include age, co-morbid infections, medication toxicity, virological, genetic and vascular mechanisms, as well as microbial translocation of lipopolysaccharide (LPS), which is suspected to trigger monocyte activation and increase trafficking of infected cells into the brain. In this study, our aim was to assess the degree of neurocognitive impairment in a group of randomly selected HIV-infected patients and investigate potential risk factors, including LPS plasma levels. Furthermore, we evaluated the relevance of LPS as a potential marker for screening patients with mild neurocognitive impairment. LPS plasma levels were compared among patients with HAND and those with no HAND. As LPS has also been shown to be elevated in hepatitis C co-infection, the analysis was stratified according to the presence or not of hepatitis C virus (HCV) co-infection. Differences between groups were evaluated using chi-square tests and Kruskal-Wallis non-parametric tests. Stepwise logistic regression was performed to identify independent risk factors for HAND in the subgroups of HCV-positive and negative patients. A p value <0.05 was considered significant. Analyses were conducted using SPSS® software. From December 2007 to July 2009, 179 patients were tested (mean age 44, 73 % male, 87 % on treatment, 30 % HCV co-infected, median CD4 504/ml and 67 % with viral load below 40 copies/ml). HAND was identified in 40/179 patients (22 %), the majority displaying asymptomatic neurocognitive impairment or mild neurocognitive disorder. Univariate analysis showed that age, illicit drug use, hepatitis C co-infection, prior AIDS-defining events, CD4/CD8 ratio and LPS plasma levels were significantly associated with HAND. The median LPS level was 98.2 pg/ml in the non-HAND group versus 116.1 pg/ml in the HAND group (p < 0.014). No differences were found in LPS values between subgroups of impairment. There was a clear association between LPS levels and HAND in the HCV-positive group (p = 0.036), while there was none in the HCV-negative group (p = 0.502). No difference in degree of hepatic fibrosis was found between the HAND and non-HAND groups. In conclusion, LPS levels were associated with HAND in the HCV-positive group, while, in the HCV-negative group, age and pro-viral DNA were the only variables independently associated with HAND. There was no difference in degree of liver disease as predicted by score of fibrosis between HAND and non-HAND groups. The role of HCV co-infection and higher LPS levels in the pathogenesis of HAND in patients with viral suppression on treatment requires further investigation.

Ramsay Hunt syndrome associated with tocilizumab therapy in rheumatoid arthritis: a case report

Ramsay Hunt syndrome associated with tocilizumab therapy in rheumatoid arthritis: a case report

Patterns of Comorbid Infections and Associated Suicidal Ideations among Individuals Attending HIV/AIDS Clinic in Benin City

Background Several literatures have documented patterns of comorbid infections among HIV/AIDS patients. Also, these patients have been found to have significant rates of suicidality. However, most of these studies have been conducted outside our population. Aim The main aim of this study was to investigate the pattern of comorbid infections among HIV/AIDS patients in our local population and to relate this to presence of suicidal ideations. Method This study involved 150 consecutive adult patients attending the HIV clinic at the University of Benin Teaching Hospital, (UBTH). They were assessed for suicidal ideations using the Beck Depression Inventory (item 9) and presence of comorbid infections was ascertained from their medical records with the help of the attending physicians. A questionnaire was administered to collect socio-demographic data. Consent was obtained from the patients and hospital authorities. Data was analysed using SPSS- 16. Results 119 females and 31 males participated. Mean age of females was 35.16 ± 9.526 and males were 37.20 ± 9.908. The types and frequencies of comorbid infections were: Vaginal Candidiasis 1 (0.78%), Herpes zoster 7 (4.9%), Oral thrash 2 (1.4%), Pelvic Inflammatory Disease 1 (0.7%), Pulmonary Tuberculosis 30 (21%), Tuberculosis Adenitis 2 (1.4%) and Genital warts 3 (2.1%). 63 (42%) of the participants had suicidal ideations and this was found to be significantly higher among those who had comorbid infections (X2=20.695, p=0.001). The most common comorbid infection was pulmonary tuberculosis (21%) and this was significantly more associated with suicidal ideations (X2=30.552, p=0.002). Suicidal ideations were found higher among female participants (X2=9.88, p=0.002) but there was no difference in rates of comorbid infections between both sexes. Conclusion There is significant presence of comorbid infections (especially Tuberculosis) among patients with HIV/AIDS and this is associated with increased rates of suicidality. Thus, a multi- disciplinary management should be in place in the care of HIV/AIDS patients.

Vaccination in rheumatology: the present and prospects

In modern rheumatology, comorbid infections (CIs) have a great impact on morbidity and mortality, in systemic connective tissue diseases in particular. In this connection, much attention is given to the intense introduction of different vaccines into rheumatological care. Much evidence suggests that immunization has no negative influence on the course of the underlying rheumatic disease (RD). The efficiency and safety of vaccination to prevent respiratory tract infections as the most important CIs are demonstrated. The fundamentals of the EULAR vaccination guidelines and the key areas of future investigations into this problem are presented.

Comorbid Infections of Pediatric Inflammatory Skin Diseases

Comorbid Infections of Pediatric Inflammatory Skin Diseases

Two children with differing outcomes after treatment for pulmonary tuberculosis diagnosed after allogeneic hematopoietic stem cell transplantation

Tuberculosis (TB) is a rare infectious complication after hematopoietic stem cell transplantation (HSCT), but may be more significant in areas where the disease is endemic. Here, we present the clinical course of 2 children with acute lymphoblastic leukemia who were diagnosed with pulmonary TB after allogeneic HSCT. Both patients were treated for either probable or possible invasive fungal infection, as well as TB. One patient, diagnosed with TB 3 months after HSCT, showed remittent fever and symptoms that progressed to acute respiratory distress syndrome and death, despite 3 modifications to the anti-TB regimen. In contrast, another patient who was diagnosed with TB 8 months after transplantation, responded well to anti-TB medication and completed 1 year of treatment with resolution of lung lesions. Co-morbid opportunistic infections, profound host immunosuppression early after transplantation, and potential risk of multi-drug resistant-TB may act as major barriers to effective treatment of TB after HSCT despite appropriate anti-TB medication.

A prospective large-scale study of methods for the detection of latent Mycobacterium tuberculosis infection in refugee children

BackgroundDiagnosis of latent tuberculosis infection (LTBI) is a cornerstone of the health assessment of resettled high incidence populations, particularly in children. Two blood-based interferon γ release assays (IGRAs), T-SPOT.TB and...

Associations Between Helicobacter pylori Infection, Co‐Morbid Infections, Gastrointestinal Symptoms, and Circulating Cytokines in African Children

Refugee children have complex medical needs and often have multiple infections. The relationship between infection, gastrointestinal symptoms, and systemic inflammation is poorly understood. We investigated these parameters in refugee children with a high prevalence of Helicobacter pylori, helminth, and malaria infection. African refugee children were recruited at resettlement health screening. Data were collected on demography, gastrointestinal symptoms, co-morbid infection, and serum for peripheral cytokine levels. Helicobacter pylori infection was diagnosed by a fecal-based immunoassay. Data from 163 children were analyzed, of which 84.0% were positive for H. pylori. Infected children were significantly older (9.2 years +/- 3.7 vs 7.1 years +/- 3.9, p = .01). Half the cohort (84/163, 51.5%) described gastrointestinal symptoms but these were not strongly associated with co-morbid infections. Helicobacter pylori-infected children had significantly lower circulating log-interleukin-8 (IL-8) (odds ratio 0.61, 95% confidence interval (CI) 0.40, 0.94, p = .025). Helminth infections were common (75/163, 46%) and associated with elevated log-IL-5 (beta: 0.42, 95% CI 0.077, 0.76). Children with malaria (15/163, 9.2%) had elevated log-tumor necrosis factor-alpha (TNFalpha) and log-IL-10 (beta: 0.67, 95% CI 0.34, 1.0 and beta: 1.3, 95% CI 0.67, 1.9, respectively). IL-10 : IL-12 ratios were increased in H. pylori-infected children with malaria or helminth infections. Symptoms were generally not associated with levels of circulating peripheral cytokines irrespective of co-morbid infection diagnosis. There is a high prevalence of asymptomatic H. pylori infection in recently resettled African refugee children. Gastrointestinal symptoms were not predictive of H. pylori nor of helminth infections. Serum cytokines, particularly IL-5, IL-10, and TNFalpha, were significantly elevated in children with malaria and helminth infections but not in those with H. pylori infection.

Neuromuscular diseases associated with HIV‐1 infection

Neuromuscular disorders are common in human immunodeficiency virus (HIV); they occur at all stages of disease and affect all parts of the peripheral nervous system. These disorders have diverse etiologies including HIV itself, immune suppression and dysregulation, comorbid illnesses and infections, and side effects of medications. In this article, we review the following HIV-associated conditions: distal symmetric polyneuropathy; inflammatory demyelinating polyneuropathy; mononeuropathy; mononeuropathy multiplex; autonomic neuropathy; progressive polyradiculopathy due to cytomegalovirus; herpes zoster; myopathy; and other, rarer disorders.

An insight into the relationships between hepcidin, anemia, infections and inflammatory cytokines in pediatric refugees: a cross-sectional study.

BackgroundHepcidin, a key regulator of iron homeostasis, is increased in response to inflammation and some infections, but the in vivo role of hepcidin, particularly in children with iron deficiency anemia (IDA) is unclear. We investigated the relationships between hepcidin, cytokines and iron status in a pediatric population with a high prevalence of both anemia and co-morbid infections.Methodology/Principal FindingsAfrican refugee children <16 years were consecutively recruited at the initial post-resettlement health check with 181 children meeting inclusion criteria. Data on hematological parameters, cytokine levels and co-morbid infections (Helicobacter pylori, helminth and malaria) were obtained and urinary hepcidin assays performed. The primary outcome measure was urinary hepcidin levels in children with and without iron deficiency (ID) and/or ID anaemia (IDA). The secondary outcome measures included were the relationship between co-morbid infections and (i) ID and IDA, (ii) urinary hepcidin levels and (iii) cytokine levels. IDA was present in 25/181 (13.8%). Children with IDA had significantly lower hepcidin levels (IDA median hepcidin 0.14 nmol/mmol Cr (interquartile range 0.05–0.061) versus non-IDA 2.96 nmol/mmol Cr, (IQR 0.95–6.72), p<0.001). Hemoglobin, log-ferritin, iron, mean cell volume (MCV) and transferrin saturation were positively associated with log-hepcidin levels (log-ferritin beta coefficient (β): 1.30, 95% CI 1.02 to 1.57) and transferrin was inversely associated (β: −0.12, 95% CI −0.15 to −0.08). Cytokine levels (including IL-6) and co-morbid infections were not associated with IDA or hepcidin levels.Conclusions/SignificanceThis is the largest pediatric study of the in vivo associations between hepcidin, iron status and cytokines. Gastro-intestinal infections (H. pylori and helminths) did not elevate urinary hepcidin or IL-6 levels in refugee children, nor were they associated with IDA. Longitudinal and mechanistic studies of IDA will further elucidate the role of hepcidin in paediatric iron regulation.

Emphysematous cystitis: a review of 135 cases

To review recently published data on emphysematous cystitis (EC), a potentially life-threatening condition characterized by air within the bladder wall, and that most typically affects middle-aged diabetic women. All articles published in English between 1956 and 2006 were identified using a Medline search for keywords "emphysematous cystitis", and "cystitis emphysematosa." Epidemiological, clinical, diagnostic, pathological and therapeutic data were evaluated, including risk factors such as the presence of diabetes mellitus or other comorbid emphysematous infections of the urinary tract. In all, 102 published papers, including 135 cases of EC, were reviewed; the median patient age was 66 years, 64% were women and 67% had diabetes mellitus. Most cases were diagnosed using plain films of the abdomen (84%), although more recently, computed tomography was the primary imaging method. Escherichia coli was the most commonly isolated organism. Most patients were treated with medical management alone (90%), while 10% of infections were treated with a combination of medicine and surgery. The overall death rate was 7%. EC is the most common and typically the least severe gas-forming infection of the urinary tract. Prompt diagnosis and treatment is warranted to prevent the potential morbidity and mortality of this infectious condition.

Multiplex PCR-based DNA array for simultaneous detection of three human herpesviruses, EVB, CMV and KSHV

Human lymphotropic herpesviruses, Epstein–Barr virus (EBV), cytomegalovirus (CMV) and Kaposi's sarcoma-associated herpesvirus (KSHV) are responsible for a wide variety of human diseases. Due to an increase in diseased states associated with immunosuppression, more instances of co-morbid infections with these herpesviruses have resulted in viral reactivations that have caused numerous fatalities. Therefore, the development of rapid and accurate method to detect these viruses in immunocompromised patients is vital for immediate treatment with antiviral prophylactic drugs. In this study, we developed a new multiplex PCR method coupled to DNA array hybridization, which can simultaneously detect all three human herpesviruses in one single cell sample. Multiplex PCR primers were designed to amplify specific regions of the EBV (EBER1), CMV (IE) and KSHV (LANA) viral genomes. Pre-clinical application of this method revealed that this approach is capable of detecting as few as 1 copy of the viral genomes for KSHV and CMV and 100 copies of the genome for EBV. Furthermore, this highly sensitive test showed no cross-reactivity among the three viruses and is capable of detecting both KSHV and EBV viral genomes simultaneously in the lymphoblastoid cells that have been double infected with both viruses. Thus, this array-based approach serves as a rapid and reliable diagnostic tool for clinical applications.

The Infection Risk of Intrathecal Drug Infusion Pumps after Multiple Refill Procedures

The objective of this study was to evaluate the long-term infection risk from refilling intrathecal drug delivery devices. We studied 25 patients (14 females and 11 males) with intrathecal infusion pumps placed for spasticity (23 patients) and chronic pain (two patients). In this study group there were 890 refill procedures (mean 35.6±20.5; range 8-72 times) performed on an outpatient basis by four different physicians. All refill procedures were performed in a sterile and standardized fashion as suggested by the manufacturer, using manufacturer's approved kits for the refills. During the study period, five patients had recurrent infection of the urinary tract and three patients had recurrent infections of the respiratory tract. At the last pump refill of each patient, residual drug, extracted from the pump reservoir, was sent to a laboratory for aerobic and anaerobic cultures. All cultures, in all pumps, were negative for aerobic and anaerobic bacteria. We conclude that periodic refills of intrathecal implanted pumps do not seem to be a risk factor for infection if standard sterile refill procedures are performed. In this study, it was clear that comorbid infections from other parts of the body do not present as a risk for device contamination.

Hepatitis B and C viral load changes following initiation of highly active antiretroviral therapy (HAART) in patients with advanced HIV infection

Chronic infection with either hepatitis B (HBV) or hepatitis C virus (HCV) is frequently present in patients seropositive for human immunodeficiency virus (HIV) because of shared routes of transmission. With the advent of highly active antiretroviral therapy (HAART) regimens capable of controlling HIV replication and dramatically prolonging the survival of HIV-infected patients, the impact of co-morbid infections such as HBV and HCV has come into focus. Several studies have monitored HBV or HCV viral loads following initiation of HAART, with disparate results. The effects of HAART on hepatitis B and C plasma viral loads ( n=9 and 32, respectively) and on liver enzyme levels were studied in a large cohort of prospectively studied subjects with advanced stage HIV disease. Comparing the mean pre- and post-HAART levels, there was an estimated increase of (a) 1.40 log 10 from 4.83 to 6.24 log 10 for HBV plasma viral load ( P=0.07), (b) 0.74 log 10 from 6.38 to 7.12 log 10 for HCV plasma viral load ( P=0.001), and (c) 19.4 U/L from 37.4 to 56.8 U/L for serum alanine aminotransferase ( P<0.001). While the number of subjects co-infected with HIV and HBV was limited, these data collected in a population of advanced stage HIV-infected patients raises questions regarding the interactions of these viruses with each other and the host immune system and has implications regarding the order in which antiviral therapies are initiated.

Hepatitis B and C viral load changes following initiation of highly active antiretroviral therapy (HAART) in patients with advanced HIV infection*1

Chronic infection with either hepatitis B (HBV) or hepatitis C virus (HCV) is frequently present in patients seropositive for human immunodeficiency virus (HIV) because of shared routes of transmission. With the advent of highly active antiretroviral therapy (HAART) regimens capable of controlling HIV replication and dramatically prolonging the survival of HIV-infected patients, the impact of co-morbid infections such as HBV and HCV has come into focus. Several studies have monitored HBV or HCV viral loads following initiation of HAART, with disparate results. The effects of HAART on hepatitis B and C plasma viral loads ( n =9 and 32, respectively) and on liver enzyme levels were studied in a large cohort of prospectively studied subjects with advanced stage HIV disease. Comparing the mean pre- and post-HAART levels, there was an estimated increase of (a) 1.40 log 10 from 4.83 to 6.24 log 10 for HBV plasma viral load ( P =0.07), (b) 0.74 log 10 from 6.38 to 7.12 log 10 for HCV plasma viral load ( P =0.001), and (c) 19.4 U/L from 37.4 to 56.8 U/L for serum alanine aminotransferase ( P <0.001). While the number of subjects co-infected with HIV and HBV was limited, these data collected in a population of advanced stage HIV-infected patients raises questions regarding the interactions of these viruses with each other and the host immune system and has implications regarding the order in which antiviral therapies are initiated.

Immune function is impaired in iron-deficient, homebound, older women

Aging is often associated with a dysregulation of immune function. Iron deficiency may further impair immunity in older adults. Published reports on iron deficiency and immune response in humans are inconsistent. Most studies are focused on young children in developing countries and are often confounded by comorbid conditions, infections, and nutrient deficiencies. Our objective was to determine the relation of iron status with immune function in homebound older women, who often have impairments in both iron status and immune response. The subjects were selected according to rigorous exclusion criteria for disease, infection, and deficiencies in key nutrients known to affect immunocompetence. Seventy-two homebound elderly women provided blood for comprehensive evaluation of iron status and cell-mediated and innate immunity. Women were classified as iron-deficient or iron-sufficient on the basis of multiple abnormal iron status test results. Groups were compared with respect to lymphocyte subsets, phagocytosis, oxidative burst capacity, and T cell proliferation upon stimulation with mitogens. In iron-deficient women, T cell proliferation upon stimulation with concanavalin A and phytohemagglutinin A was only 40-50% of that in iron-sufficient women. Phagocytosis did not differ significantly between the 2 groups, but respiratory burst was significantly less (by 28%) in iron-deficient women than in iron-sufficient women. Iron deficiency is associated with impairments in cell-mediated and innate immunity and may render older adults more vulnerable to infections. Further prospective studies using similar exclusion criteria for disease, infection, and concomitant nutrient deficiencies are needed for simultaneous examination of the effects of iron deficiency on immune response and morbidity.

Treatment and prevention of otitis media.

To review and summarize recent advances in the treatment and prevention of otitis media (OM). A MEDLINE search (1996-March 2000) was performed to identify relevant primary and review articles. References from these articles were also reviewed if deemed important. English-language primary and review articles focusing on the treatment and prevention of acute otitis media (AOM) were included. Studies focusing exclusively on OM with effusion or serous OM and chronic suppurative OM were excluded. Information regarding prevention and drug therapy was reviewed, with an emphasis placed on advances made in the last two years. Recently, an expert panel of the Centers for Disease Control and Prevention recommended use of only three of 16 systemic antibiotics approved by the Food and Drug Administration for treatment of AOM: amoxicillin, cefuroxime axetil, and ceftriaxone. Controversy exists over the importance of key selection factors used by the expert panel in determining which antibiotics to recommend in a two-step treatment algorithm, that is, in vitro data, pharmacodynamic profiles, and necessity for coverage of drug-resistant Streptococcus pneumoniae at all steps of empiric treatment. Additional antibiotic and patient selection factors useful for individualizing therapy include clinical efficacy, adverse effects, frequency and duration of administration, taste, cost, comorbid infections, and ramifications should bacterial resistance develop to the chosen antibiotic. Presumed or past patient/caregiver adherence (especially when antibiotic failure has occurred) is also paramount in selecting antibiotic therapy. A three-step treatment algorithm for refractory AOM that employs amoxicillin, trimethoprim/sulfamethoxazole (TMP/SMX), or high-dose amoxicillin/clavulanate (depending on the prior dose of and adherence to amoxicillin therapy), and ceftriaxone or tympanocentesis at steps 1, 2, and 3, respectively, appears rational and cost-effective. The recent upsurge in antimicrobial resistance is highlighted, and recommendations are presented for the treatment of AOM and prevention of recurrent otitis media (rAOM). Amoxicillin remains the antibiotic of choice for initial empiric treatment of AOM, although the traditional dosage should be increased in patients at risk for drug-resistant S. pneumoniae. In cases refractory to high-dose amoxicillin, TMP/SMX should be prescribed if adherence to prior therapy seemed good or complete, or high-dose amoxicillin/clavulanate if adherence was incomplete or questionable. Ceftriaxone should be reserved as third-line treatment. The increasing prevalence of drug-resistant S. pneumoniae emphasizes the importance of alternative medical approaches for the prevention of OM, as well as judicious antibiotic use in established cases. Removal of modifiable risk factors should be first-line therapy for prevention of rAOM. We support the use of conjugate pneumococcal vaccine per guidelines for prevention of rAOM from the Advisory Committee on Immunization Practice of the Centers for Disease Control and Prevention, with consideration given to influenza vaccine for cases of rAOM that historically worsen during the flu season. Sulfisoxazole prophylaxis should be reserved for children who are immunocompromised, have concurrent disease states exacerbated by AOM, or meet the criteria of rAOM despite conjugate pneumococcal and influenza vaccination. Therapy should be intermittent, beginning at the first sign of an upper respiratory infection, and should continue for 10 days. The invasive nature and risks of anesthesia relegate myringotomy, tympanostomy tubes, and adenoidectomy to last-line therapies for rAOM.