Appropriate antibiotic use in dentistry: a review of the literature and clinical recommendations.

This article reviews the latest evidence on the use of antibiotics in dentistry, beginning with the risks of antibiotic use, which include Clostridioides difficile infection and antimicrobial resistance. The article then reviews the clinical practice guidelines for antibiotic prophylaxis for patients with prosthetic joints or at high risk for infective endocarditis. In the absence of established guidelines, the discussion also examines the published evidence on best practices for antibiotic prophylaxis with regard to other medical conditions (eg, kidney disease, cancer, or immunosuppression), dental extractions, minor oral surgical procedures, and implant placement, offering sample prescriptions for these situations. In addition, the current clinical practice guideline for antibiotic use in patients with endodontic infections is reviewed. Due to the alarming rates of antibiotic-resistant bacterial infections and increasing antimicrobial resistance, it is imperative that dentists use evidence-based guidelines and recommendations when prescribing antibiotics to prevent and treat oral infections.

Assessment of the current knowledge about infective endocarditis prevention among dental hygienists in Italy: A national survey.

OBJECTIVES: To date, there is a lack of data regarding the acceptance of the guidelines for infective endocarditis (IE) prevention among dentists in Italy, and similarly, there are no data on the understanding and compliance of those among dental hygienists (DH). Thus, we tried to assess the ability of DH to recognize and manage categories of patients at high risk of EI, to identify which dental procedures are at increased risk and to assess the level of knowledge of doses and how antibiotic prophylaxis should be administered in specific cases. METHODS: An anonymous questionnaire was prepared and made accessible online by sharing a Google Forms® link; general personal data and educational background information were collected to obtain a profile of the participants. RESULTS: A total of 362 DH answered to our web-based survey, showing a prevalent female percentage (86.7%) and the most represented age group of 30-39 years old (43.1%). Regarding the gender differences, there were not overall statistically significant differences; similarly, we did not find any differences regarding the overall number of wrong questions if considering the different ages of the participant and the year of graduation. Graduates in Northern Italy have mistaken fewer questions than graduates in other geographical areas. CONCLUSION: To the best of our knowledge, this is the largest survey about the knowledge of IE for DH ever performed. Because the overprescription of antibiotics contributes to the development of drug resistance, antibiotic stewardship should be at the forefront of patient care. Our data reflect the need for placing a greater emphasis on IE prophylaxis education in training and during continuing professional development events for DH.

Recent infective endocarditis research findings suggest dentists prescribe prophylactic antibiotics for patients having a bicuspid aortic valve or mitral valve prolapse.

BACKGROUND: The scientific validity of the European Society of Cardiology's (ESC) infective endocarditis (IE) guidelines limiting provision of prophylactic antibiotics (AP) only to patients having cardiac anomalies (e.g., prosthetic valves) believed to place them at "high risk" of adverse events when undergoing high risk dental procedures (HRDP) is unclear. MATERIAL AND METHODS: A systematic review of studies conducted between 2017 and 2022 and catalogued in the PubMed database was undertaken to ascertain if this edict was associated with changes in IE incidence, development of infection in unprotected cardiac anomalies, developing infection and resultant adverse clinical outcomes. RESULTS: Retrieved were 19 published manuscripts, however of these, 16 were excluded because they did not bare upon the issues of concern. Among the three studies eligible for review were those in the Netherlands, Spain, and England. The results of the Dutch study denoted a significant increase in the incidence of IE cases over the projected historical trend (rate ratio: 1327, 95% CI 1.205-1.462; p<0.001) after the introduction of the ESC guidelines. The findings from the Spanish study evidenced the uniquely high in-hospital IE associated fatality rates suffered by patients having bicuspid aortic valves (BAV); 5.6% or mitral valve prolapse (MVP); 10%. The British study provided evidence that the incidence of fatal IE infection was significantly greater among an "intermediate risk" cohort of patients, (a group likely including those with BAC and MVP for which the ESC guidelines don't recommend AP), than among "high risk" patients (P = 0.002). CONCLUSIONS: Patients having either a BAV or MVP are at significant risk of developing IE and suffering serious sequelae including death. The ESC guidelines must reclassify these specific cardiac anomalies into the "high risk" category so that AP are recognized as being needed prior to provision of HRDP.

Infective Endocarditis Among High-risk Individuals Before and After the Cessation of Antibiotic Prophylaxis in Dentistry: A National Cohort Study.

BACKGROUND: A few years after the publication of the British guidelines, national recommendations were published by the Swedish Medical Products Agency in October 2012, promoting the cessation of antibiotic prophylaxis in dentistry for the prevention of infective endocarditis (IE). The aim of this study was to evaluate whether the incidence of oral streptococcal IE increased among high-risk individuals after October 2012. METHODS: This nationwide cohort study included all adult individuals (>17 years) living in Sweden from January 2008 to January 2018, with a diagnose code or surgical procedure code indicating high risk of IE. Cox proportional hazard models were performed to calculate adjusted ratios of oral streptococcal IE before and after October 2012 between high-risk individuals and references. RESULTS: This study found no increased incidence of oral streptococcal IE among high-risk individuals during the 5 years after the cessation, compared with before. Hazard rate ratios were 15.4 (95% confidence interval [CI]: 8.3-28.5) before and 20.7 (95% CI: 10.0-42.7) after October 2012 for prevalent high-risk individuals. Corresponding ratios for incident high-risk individuals were 66.8 (95% CI: 28.7-155.6) and 44.6 (95% CI: 22.9-86.9). Point estimates for interaction with time period were 1.4 (95% CI: .6-3.5) and 0.8 (95% CI: .5-1.3) for prevalent and incident high-risk individuals, respectively. CONCLUSION: The results suggest that the current Swedish recommendation not to administer antibiotic prophylaxis for the prevention of IE in dentistry has not led to an increased incidence of oral streptococcal IE among high-risk individuals.

Antibiotic prescription after tooth extraction in adults: a retrospective cohort study in Austria.

BACKGROUND: Broad spectrum antibiotics are often used for the prophylaxis of infectious endocarditis and treatment of odontogenic infections, but there are limited data related to antibiotic use and adherence to prescription guidelines.  METHODS: Data from patients with tooth extraction between 2014 and 2018 were selected from a database of a regional health insurance fund. We created three data sets, one based on all tooth extractions, one on multiple teeth extractions, and one including only single tooth extraction. After data collection, descriptive analysis was carried out. The differences in prescription pattern of antibiotic medicine were tested by χ2 test, Student´s t-test or ANOVA. RESULTS: From 43,863 patients with tooth extraction, 53% were female, and 3,983 patients (9.1%) filled a prescription for antibiotic medicine. From 43,863 patients, 157 patients (0.4%) had endocarditis risk, but only 8 patients of these (5.1%) filled an antibiotic prescription. In total, 9,234 patients had multiple and 34,437 patients had only one tooth extraction. Patients with more than one tooth extraction received more often antibiotic treatment (10.7%) compared to those with single tooth extractions (χ2 = 36; p < 0,001). Patients with more than one tooth extraction were older, however, younger patients received antibiotics more frequently (t = 28,774, p = 0.001). There was no relationship with endocarditis risk status. Clindamycin and amoxicillin/clavulanic acid were the most frequently prescribed antibiotic medicines. CONCLUSIONS: In this retrospective cohort study, dentists did not discriminate prophylactic antibiotic prescription with regard to endocarditis risk status. A factor influencing prescribing behaviour of antibiotic medicines was the number of extracted teeth.

Dentists' knowledge and practices about infective endocarditis antibiotics prophylaxis among children in aseer region, Southwestern Saudi Arabia.

BACKGROUND: Infective endocarditis (IE) is a disease endangering human lives. Therefore, several prophylactic measures are required to improve the protection of endocarditis-prone patients from bacteremia resulting from various dental actions. These measures range from developing the dental hygiene to trials of different antimicrobial agents. OBJECTIVES: To examine the knowledge and practices of dentists in Aseer Region, Saudi Arabia, regarding antibiotic prophylaxis against IE. DESIGN: Cross-sectional study. SETTING: Aseer Region, Saudi Arabia. PATIENTS AND METHODS: The participants were interviewed at their workplaces and the data collection sheet was constructed based on the guidelines of the American Heart Association/American College of Cardiology (AHA/ACC, 2017). MAIN OUTCOME MEASURES: The examination of the data gathered was calculated using Statistical Package for Social Sciences (SPSS, version 25) such as to test the significance of variation in dentists' mean knowledge scores as per their personal characteristics. An output with P values <0.05 was statistically significant. SAMPLE SIZE: 182 Dentists. RESULTS: Dentists' mean knowledge score was 17.5 ± 3.7 (out of 24). The least correct responses regarding dental procedures that require prophylactic antibiotics were "root canal treatment" (30.8%). Regarding cardiac conditions that require prophylactic antibiotics, dentists' least correct responses were "heart failure" (50%). Dentists' mean knowledge scores differed significantly according to their age groups (P = 0.032), nationality (P = 0.002), education/qualification (P = 0.002). Mean knowledge scores differed significantly according to dentists' years of experience (P = 0.018) and sources of information (P < 0.001). Amoxicillin was the most regularly recommended antibiotic (90.7%), while 86.8% correctly stated 30--60 min. before the procedure as the time for prophylactic antibiotic administration. CONCLUSIONS: The knowledge of dentists in Aseer Region regarding the use of preventive drugs for the control and prevention of IE is suboptimal. The inclusion of the latest AHA guidelines into the dentistry curricula is highly recommended. LIMITATIONS: Outcome are simultaneously assessed.

A Challenge of COVID-19: Associated Infective Endocarditis with Streptococcus gordonii in a Young Immunocompetent Patient.

The COVID-19 pandemic is a new challenge for the diagnosis and treatment of infective endocarditis (IE). Fever and other unspecific symptoms of coronaviral infection could be misleading or masking its manifestations. We present the case of a young patient admitted for persistent fever, profuse sweating, headache, articular pain, myalgias, and weight loss. She reported regression taste and smell disorders compared to a month earlier when diagnosed with moderate COVID-19 pneumonia. While the RT-PCR SARS-COV-2 test was positive, she was admitted to a COVID-19 ward. Investigations of febrile syndrome revealed two positive blood cultures with Streptococcus gordonii and the presence of vegetations on the aortic valve, supporting a certain diagnosis of IE. After six weeks of antibiotic treatment, the patient had clinical and biologic favorable outcomes. Streptococcus gordonii is a common commensal related to the dental biofilm, although there were no caries in our patient. The influence of COVID-19 infection on the human microbiome by modifying the virulence of some commensal germs may be a risk factor for IE pathogenesis on native valves and requires the vigilance of clinicians for suspicion of this disease.

Review of Guidelines for Dental Antibiotic Prophylaxis for Prevention of Endocarditis and Prosthetic Joint Infections and Need for Dental Stewardship.

Dentists prescribe 10% of all outpatient antibiotic prescriptions, writing more than 25.7 million prescriptions per year. Many are for prophylaxis in patients with prosthetic joint replacements; the American Dental Society states that "in general," prophylactic antibiotics are not recommended to prevent prosthetic joint infections. Orthopedic surgeons are concerned with the risk of implant infections following a dental procedure and, therefore, see high value and low risk in recommending prophylaxis. Patients are "stuck in the middle," with conflicting recommendations from orthopedic surgeons (OS) and dentists. Unnecessary prophylaxis and fear of lawsuits amongst private practice dentists and OS has not been addressed. We review The American Heart Association/American College of Cardiology, American Dental Association, and American Association of Orthopedic Surgeons' guidelines on dental antibiotic prophylaxis for the prevention of endocarditis and prosthetic joint infections. We provide experience on how to engage private-practice dentists and OS in dental stewardship using a community-based program.

The Cost-Effectiveness of Antibiotic Prophylaxis for Patients at Risk of Infective Endocarditis.

BACKGROUND: In March 2008, the National Institute for Health and Care Excellence recommended stopping antibiotic prophylaxis (AP) for those at risk of infective endocarditis (IE) undergoing dental procedures in the United Kingdom, citing a lack of evidence of efficacy and cost-effectiveness. We have performed a new economic evaluation of AP on the basis of contemporary estimates of efficacy, adverse events, and resource implications. METHODS: A decision analytic cost-effectiveness model was used. Health service costs and benefits (measured as quality-adjusted life-years) were estimated. Rates of IE before and after the National Institute for Health and Care Excellence guidance were available to estimate prophylactic efficacy. AP adverse event rates were derived from recent UK data, and resource implications were based on English Hospital Episode Statistics. RESULTS: AP was less costly and more effective than no AP for all patients at risk of IE. The results are sensitive to AP efficacy, but efficacy would have to be substantially lower for AP not to be cost-effective. AP was even more cost-effective in patients at high risk of IE. Only a marginal reduction in annual IE rates (1.44 cases in high-risk and 33 cases in all at-risk patients) would be required for AP to be considered cost-effective at £20 000 ($26 600) per quality-adjusted life-year. Annual cost savings of £5.5 to £8.2 million ($7.3-$10.9 million) and health gains >2600 quality-adjusted life-years could be achieved from reinstating AP in England. CONCLUSIONS: AP is cost-effective for preventing IE, particularly in those at high risk. These findings support the cost-effectiveness of guidelines recommending AP use in high-risk individuals.

[Management of biofilm-associated infections: what can we expect from recent research on biofilm lifestyles?]. / Infections associées aux biofilms: quelles perspectives thérapeutiques issues de la recherche fondamentale?

Biofilms are surface-associated microbial communities present in all environments. Although biofilms play important ecological roles, they also lead to negative or deleterious effects in industrial and medical settings. In the latter, high levels of antibiotic tolerance of bacterial biofilms developing on medical devices and during chronic infections determine the physiopathology of many healthcare-associated infections. Original approaches have been developed to avoid bacterial adhesion or biofilm development targetting specific mechanisms or pathways. We herein review recent data about biofilm lifestyle understanding and ways to fight against related infections.

[Is infective endocarditis prophylaxis always recommended?]. / La prophylaxie de l'endocardite infectieuse est-elle toujours recommandée?

Infective endocarditis prophylaxis is a preventive strategy that has been recommended in various countries for more than 50 years. It is based on the plausible assumption that infectious endocarditis is, at least partially, avoidable. Traditionally, prophylaxis has consisted in the administration of an antibiotic agent in subjects with high-risk heart disease, or before high-risk interventions. More than 20 years ago, the indications of antibiotic prophylaxis were reduced and limited to high-risk patients and interventions, essentially valve replacement, or dental procedures with mucosal involvement, while the recommendations for overall non-antibiotic preventive measures, as well as recommendations for earlier diagnosis, have been reinforced.

Quality appraisal of antibiotic prophylaxis guidelines to prevent infective endocarditis following dental procedures: a systematic review.

OBJECTIVE: To assess the quality of clinical practice guidelines (CPGs) for the use of antimicrobial prophylaxis to prevent infective endocarditis in indicated dental procedures. STUDY DESIGN: We searched on Medline/OVID, CINAHL/EBSCO, and EMBASE from January 2011 to January 2022. We included de novo guidelines and excluded adapted or adopted guidelines, and guidelines published before 2011. The guidelines were independently appraised by 4 reviewers using the Appraisal of Guidelines for Research & Evaluation II (AGREE II) Instrument. RESULTS: Four eligible CPGs were appraised: the European Society of Cardiology, the American Heart Association, the National Institute of Health and Care Excellence (NICE), and the Japanese Circulation Society (JCS). Their AGREE II first overall assessments (OA1) were 63%, 58%, 92%, and 71%, respectively. Both NICE and JCS scored the highest in OA1 (>70%), Domain 3 Rigor of Development (85%, 65%), and Domain 5 Applicability (76%, 48%), respectively. The second overall assessment (OA2) of using the CPGs in daily practice was not significantly variable (recommended for use with modifications). CONCLUSION: Three out of 4 CPGs support that the benefits of prevention of infective endocarditis outweigh the risks of antibiotic resistance.

Infective endocarditis in patients with rheumatic heart disease: a single-centre retrospective comparative study.

AIMS: We reviewed the baseline characteristics and outcomes of patients with infective endocarditis (IE) and compared those with and without rheumatic heart disease (RHD). METHODS: We retrospectively reviewed patients ≥15 years with IE treated at Auckland City Hospital between January 2016 and December 2018 and excluded device-related IE and complex congenital heart disease. RHD status was based on echocardiographic features or previous history of rheumatic fever with valvular disease. Microbiologic and echocardiographic results, treatment modalities and complications were recorded. Demographics and outcomes were compared based on RHD status. RESULTS: There were 155 patients with IE. Twenty-two had RHD. The mean age at admission was 45 years for RHD patients, which was 19 years younger than for non-RHD patients. There were significantly more Pacific patients with RHD (55% vs 14%). Previous IE and prosthetic valve endocarditis (PVE) were more common in RHD patients (27% vs 5%, and 77% vs 29%, respectively). After a median follow-up of 29 months, there was no significant difference in all-cause mortality between the two groups. However, 25/155 patients (16%) had died from IE-related causes (septic or cardiogenic shock post cardiac surgery, or embolic complications), with a significantly higher mortality in patients with RHD (7/22 (32%) patients, HR: 2.5) on univariate analysis. On multivariable analysis, PVE, heart failure, Staphylococcus aureus infection, diabetes, stroke and cardiac abscess were all associated with increased mortality, whereas RHD was not independently associated with increased mortality. CONCLUSIONS: In this retrospective single-centre audit, patients with RHD experienced IE at a younger age, had a higher incidence of prosthetic valve endocarditis and a prior history of IE. Although there was no difference in all-cause mortality, mortality in patients with RHD was almost exclusively secondary to complications of IE. This highlights the need for prevention strategies against endocarditis in the RHD population, including use of antibiotic prophylaxis¬, accessible dental health care and a high clinical suspicion for IE in RHD by healthcare providers.

A Rare Case of Emphysematous Endocarditis Caused by Escherichia coli.

Infective endocarditis (IE) is an infection of the heart endocardium with significant morbidity and mortality. Gram negative infection, particularly emphysematous IE, is an extremely rare and life-threatening disease. We report a 59-year-old diabetic female patient who was admitted to a secondary care hospital in Rustaq, Oman, in 2017 with the diagnosis of pneumonia for which she was started on antibiotics. Shortly afterwards, she developed facial and mouth deviation and became more tachypneic. Computed tomography of the brain demonstrated bilateral multiple small infarcts. Pulmonary angiography computed tomography was performed which ruled out pulmonary embolism. Nonetheless, it revealed an air-containing lesion around the mitral valve. Transthoracic echocardiography demonstrated a hyperechoic mobile lesion related to the mitral valve. Blood culture grew Escherichia coli and the diagnosis of E. coli emphysematous IE was made based on modified Duke criteria. The patient's clinical condition deteriorated and she suffered cardiac arrest leading to her death. The recommended treatment for non-HACEK IE includes an extended antibiotic course and surgery for selected patients.

Infective endocarditis treated in a secondary hospital: epidemiological, clinical, microbiological characteristics and prognosis, with special reference to patients transferred to a third level hospital.

OBJECTIVE: To analyse the clinical and epidemiological characteristics and mortality-related factors of patients admitted to a secondary hospital with Infective Endocarditis (IE). METHODS: Observational study of a cohort of patients who have been diagnosed with IE in a secondary hospital and evaluated in accordance with a pre-established protocol. RESULTS: A total of 101 cases were evaluated (years 2000-2017), with an average age of 64 years and a male-to-female ratio of 2:1. 76% of the cases had an age-adjusted Charlson comorbidity index of >6, with 21% having had a dental procedure and 36% with a history of heart valve disease. The most common microorganism was methicillin-susceptible S. aureus (36%), with bacterial focus of unknown origin in 54%. The diagnostic delay time was 12 days in patients who were transferred, compared to 8 days in patients who were not transferred (p=0.07); the median surgery indication delay time was 5 days (IQR 13.5). The in-hospital mortality rate was 34.6% and the prognostic factors independently associated with mortality were: cerebrovascular events (OR 98.7%, 95% CI, 70.9-164.4); heart failure (OR 27.3, 95% CI, 10.2-149.1); and unsuitable antibiotic treatment (OR 7.2, 95% CI, 1.5-10.5). The mortality rate of the patients who were transferred and who therefore underwent surgery was 20% (5/25). CONCLUSIONS: The onset of cerebrovascular events, heart failure and unsuitable antibiotic treatment are independently and significantly associated with in-hospital mortality. The mortality rate was higher than the published average (35%); the diagnostic delay was greater in patients for whom surgery was indicated.

Brain abscess due to Aggregatibacter aphrophilus in association with atrial septal defect：Case report and literature review.

BACKGROUND: Aggregatibacter aphrophilus（A. aphrophilus）is one of the organisms of the HACEK group. Previously reported cases of brain abscesses caused by A. aphrophilus infection have occurred in children with a basis for congenital heart disease, or in adults with a basis for dental disease. Rare cases of brain abscess caused by A. aphrophilus have been reported in adults with congenital heart disease or in patients without dental disease history. Herein we present a rare case of brain abscess caused by A. aphrophilus, who was in association with atrial septal defect for more than 20 years, and had no dental disease and did not develop infective endocarditis. CASE PRESENTATION: A 51-year-old female was admitted due to progressively worsening headache and left limb weakness for more than 10 days. She denied the history of chronic diseases such as hypertension and diabetes, and no periodontal disease. While she had a history of atrial septal defect, a form of congenital heart disease with severe pulmonary hypertension for more than 20 years. After admission, echocardiographic illustrated congenital heart disease with severe pulmonary hypertension. CT and MRI showed brain abscess. Cerebrospinal fluid (CSF) results also confirmed the presence of intracranial infection. Empirical therapy with vancomycin 1.0 g i.v q12h and meropenem 2.0 g i.v q8h was initiated from the day of admission. On the fourth day after admission, brain abscess resection and decompressive craniectomy were performed, and the pus drained on operation were cultured and Gram-negative bacilli grew, which was identified as A.aphrophilus. Vancomycin was discontinued and meropenem was continued（2.0 g i.v q8h）for 5 weeks, followed by oral levofloxacin 0.5 qd for 4 weeks of out-patient antibiotics. The patient recovered fully within 9 weeks of treatment. CONCLUSIONS: This is the first case of A. aphrophilus to cause brain abscess in adult with a history of congenital heart disease for more than 20 years, who had no dental disease and did not develop infective endocarditis. We also highlight the value of bacterial 16 S rDNA PCR amplification and sequencing in identifying bacteria in abscesses which are culture-negative, and prompt surgical treatment，choosing effective antibiotics and appropriate course of treatment will get better clinical effect.

Synthesis of silver nanoparticles using gum Arabic: Evaluation of its inhibitory action on Streptococcus mutans causing dental caries and endocarditis.

BACKGROUND: Streptococcus mutans are an oral pathogen that causes dental caries, endocarditis, and systemic dysfunctions, an alternative antibacterial solution from silver nanoparticles (AgNPs) are investigated. METHODS: AgNPs were synthesized using the ethnobotanical product gum Arabic. It influenced the nanoparticles with medicinal value through their role as capping, stabilizing, or surface-attached components. The biophysical characteristics of the synthesized AgNPs were studied using UV-vis spectrum, XRD, EDAX, SEM, and TEM tools. The AgNPs were spherical with the average size less than 10 nm. By using the well diffusion and microdilution techniques, the impact of synthesized AgNPs was tested against S. mutans isolates. RESULTS: The smaller the size, the greater the antibacterial and antiviral potential the particles exhibit. The biophysical characteristics of AgNPs the presence of phenols, alcohols, amides, sulfoxide, flavanoids, terpenoids and steroids. The AgNPs exhibited a good antibacterial action against the oral pathogen S. mutans. The synthesized NPs at a dose level of 200 µg/mL exhibited an inhibition zone with 18.30 ± 0.5 nm diameter. The synthesised nanoparticles inhibited the genes responsible for biofilm formation of S. mutans over host tooth and gums (gtfB, gtfc, gtfD) and virulent protective factors (comDE, brpA and smu 360) and survival promoter genes (gyrA and spaP, gbpB). CONCLUSION: The potent antibiotic action over S. mutans seen with the synthesized NPs, paves the way for the development of novel dental care products. Also, the small-sized NPs promote its applicability in COVID-19 pandemic containment.

Successful resolution of cardiac mycetomas by combined liposomal Amphotericin B with Fluconazole treatment in premature neonates.

This manuscript reports on two very low birth weight premature infants with respiratory distress, receiving parenteral nutrition and broad-spectrum antibiotics for about 3 weeks, who developed Candida albicans sepsis associated with fungal mycoses and endocarditis, despite treatment with Amphotericin B and Caspofungin. On days 40 and 47, respectively, antifungal therapy was modified to liposomal Amphotericin B combined with Fluconazole 6 mg/kg/day for 4 weeks, resulting in complete resolution of the mycetomas. Our observations suggest that the combination of liposomal Amphotericin B with Fluconazole is able to result in complete resolution of cardiac mycetomas in preterm infants.