George A. Syrogiannopoulos

Antibiotic therapy for pediatric community-acquired pneumonia: do we know when, what and for how long to treat?

Community-acquired pneumonia (CAP) is a common cause of morbidity among children in developed countries and accounts for an incidence of 10-40 cases per 1000 children in the first 5 years of life. Given the clinical, social and economic importance of CAP, there is general agreement that prompt and adequate therapy is essential to reduce the impact of the disease. The aim of this discussion paper is to consider critically the available data concerning the treatment of uncomplicated pediatric CAP and to consider when, how and for how long it should be treated. This review has identified the various reasons that make it difficult to establish a rational approach to the treatment of pediatric CAP, including the definition of CAP, the absence of a pediatric CAP severity score, the difficulty of identifying the etiology, limited pharmacokinetic (PK)/pharmacodynamic (PD) studies, the high resistance of the most frequent respiratory pathogens to the most widely used anti-infectious agents and the lack of information concerning the changes in CAP epidemiology following the introduction of new vaccines against respiratory pathogens. More research is clearly required in various areas, such as the etiology of CAP and the reasons for its complications, the better definition of first- and second-line antibiotic therapies (including the doses and duration of parenteral and oral antibiotic treatment), the role of antiviral treatment and on how to follow-up patients with CAP. Finally, further efforts are needed to increase vaccination coverage against respiratory pathogens and to conduct prospective studies of their impact.Community-acquired pneumonia (CAP) is a common cause of morbidity among children in developed countries and accounts for an incidence of 10–40 cases per 1000 children in the first 5 years of life. Given the clinical, social and economic importance of CAP, there is general agreement that prompt and adequate therapy is essential to reduce the impact of the disease. The aim of this discussion paper is to consider critically the available data concerning the treatment of uncomplicated pediatric CAP and to consider when, how and for how long it should be treated. This review has identified the various reasons that make it difficult to establish a rational approach to the treatment of pediatric CAP, including the definition of CAP, the absence of a pediatric CAP severity score, the difficulty of identifying the etiology, limited pharmacokinetic (PK)/pharmacodynamic (PD) studies, the high resistance of the most frequent respiratory pathogens to the most widely used anti-infectious agents and the lack of information concerning the changes in CAP epidemiology following the introduction of new vaccines against respiratory pathogens. More research is clearly required in various areas, such as the etiology of CAP and the reasons for its complications, the better definition of first- and second-line antibiotic therapies (including the doses and duration of parenteral and oral antibiotic treatment), the role of antiviral treatment and on how to follow-up patients with CAP. Finally, further efforts are needed to increase vaccination coverage against respiratory pathogens and to conduct prospective studies of their impact.

Descriptive Study on Parents' Knowledge, Attitudes and Practices on Antibiotic Use and Misuse in Children with Upper Respiratory Tract Infections in Cyprus

Upper respiratory tract infections (URTIs) are common in children and represent a significant cause of antibiotic abuse which contributes to the development of antibiotic resistance. A survey was conducted in Cyprus in 2006 to assess parents’ and pediatricians’ Knowledge, Attitude and Practices (KAP) concerning the role of antibiotics in children with URTIs. A school-based stratified geographic clustering sampling was used and a pre-tested KAP questionnaire was distributed. A different questionnaire was distributed to paediatricians. Demographic factors associated with antibiotic misuse were identified by backward logistic regression analysis. The parental overall response rate was 69.3%. Parents (N = 1,462) follow pediatricians advice and rarely administer antibiotics acquired over the counter. Although a third expects an antibiotic prescription for URTI symptoms, most deny pressuring their doctors. Low parental education was the most important independent risk factor positively related to antibiotic misuse (OR = 2.88, 95%CI 2.02 to 4.12, p < 0.001). Pediatricians (N = 33) denied prescribing antibiotics after parental pressure but admit that parents ask for antibiotics and believe they expect antibiotic prescriptions even when not needed. In conclusion, Cypriotic parents trust their primary care providers. Although it appears that antibiotic misuse is not driven by parental pressure, the pediatricians’ view differs.

Dynamics of Streptococcus pneumoniae nasopharyngeal carriage with high heptavalent pneumococcal conjugate vaccine coverage in Central Greece.

In order to study whether the use of the heptavalent pneumococcal conjugate vaccine (PCV7) led to a shift in the Streptococcus pneumoniae serotypes distribution and whether it modified the resistance to antibiotics, 2649 nasopharyngeal samples were obtained between 2005 and 2009, from children attending day-care centers in Central Greece. The percentage of attendees vaccinated with ≥1 dose of PCV7 increased from 12.9% (2005) to 95.5% (2009). Non-PCV7 serotypes replaced those belonging to PCV7. In 2009, 19F was virtually the only PCV7 serotype that continued to circulate. A significant increase in the frequency of penicillin-intermediate (oral penicillin V breakpoints) isolates coincided with a marked reduction in isolates with high resistance to penicillin. Several non-PCV7 serotypes colonized the children, but their frequency varied substantially from year to year. Each one of 14 specific non-PCV7 serotypes, i.e. 6A, 11A, 15B, 23A, 10A, 16F, 38, 22F, 15C, 19A, 35F, 24F, 6C, and 7F, accounted for ≥2% of pneumococcal isolates in at least 2 annual surveillances. An increase in non-PCV7 serotypes with antibiotic resistance, beyond 6A and 19A, occurred. Intermediate resistance to penicillin was observed in serotype 23B, 15B, 15C, 15A, 35F, 6C, and 24F pneumococci. Their exact role in invasive and non-invasive disease remains to be seen in the years ahead.

Fusidic acid and clindamycin resistance in community-associated, methicillin-resistant Staphylococcus aureus infections in children of Central Greece

IntroductionIn Greece, fusidic acid and clindamycin are commonly used for the empiric therapy of suspected staphylococcal infections.MethodsThe medical records of children examined at the outpatient clinics or admitted to the pediatric wards of the University General Hospital of Larissa, Central Greece, with community-associated staphylococcal infections from January 2003 to December 2009 were reviewed.ResultsOf 309 children (0-14 years old), 21 (6.8%) had invasive infections and 288 (93.2%) skin and soft tissue infections (SSTIs). Thirty-five patients were ≤30 days of age. The proportion of staphylococcal infections caused by a community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) isolate increased from 51.5% (69 of 134) in 2003-2006 to 63.4% (111 of 175) in 2007-2009 (P = 0.037). Among the CA-MRSA isolates, 88.9% were resistant to fusidic acid, 77.6% to tetracycline, and 21.1% to clindamycin. Clindamycin resistance increased from 0% (2003) to 31.2% (2009) among the CA-MRSA isolates (P = 0.011). Over the 7-year period, an increase in multidrug-resistant CA-MRSA isolates was observed (P = 0.004). One hundred and thirty-one (93.6%) of the 140 tested MRSA isolates were Panton-Valentine leukocidin-positive. Multilocus sequence typing of 72 CA-MRSA isolates revealed that they belonged to ST80 (n = 61), ST30 (n = 6), ST377 (n = 3), ST22 (n = 1), and ST152 (n = 1). Resistance to fusidic acid was observed in ST80 (58/61), ST30 (1/6), and ST22 (1/1) isolates.ConclusionIn areas with high rate of infections caused by multidrug-resistant CA-MRSA isolates, predominantly belonging to the European ST80 clone, fusidic acid and clindamycin should be used cautiously as empiric therapy in patients with suspected severe staphylococcal infections.

Bacterial bronchitis caused by Streptococcus pneumoniae and nontypable Haemophilus influenzae in children: the impact of vaccination.

BACKGROUND Protracted bacterial bronchitis is a major cause of persistent cough in childhood. The organisms most commonly isolated are nontypable Haemophilus influenzae and Streptococcus pneumoniae . There are no studies addressing typing of these organisms when recovered from the lower airways. METHODS Isolates of these two organisms (identified in BAL samples from children undergoing routine investigation of a chronic cough thought to be attributable to a protracted bacterial bronchitis) were subject to typing. Samples were collected in Sheffield, England, and Athens, Greece. The majority of the children from Sheffield had received pneumococcal-conjugate vaccines 7 or 13 (PCV-7 or PCV-13) conjugate vaccine but only a minority of Greek children had received PCV-7. RESULTS All 18 S pneumoniae isolates from Greek BAL samples are serotypes contained in PCV-13 while 10 are contained in PCV-7. In contrast, 28 of the 39 samples from Sheffield contained serotypes that are not included in PCV-13. All 26 of the nontypable H influenzae samples obtained in Sheffield produced distinct multilocus variable-number tandem repeat analysis profiles. There was a significant difference between children from Athens and Sheffield in the distribution of serotypes contained or not contained in the pneumococcal vaccine ( P = .04). More specifically, immunization with pneumococcal vaccine was related with isolation of S pneumoniae serotypes not included in the vaccine (OR, 0.021; CI, 0.003-0.115; P < .001). CONCLUSIONS The data suggest that both vaccine and nonvaccine S pneumoniae serotypes may play a role in protracted bacterial bronchitis and provide some hints that serotype replacement may occur in response to the introduction of conjugate vaccines.

Original ResearchChest InfectionsBacterial Bronchitis Caused by Streptococcus pneumoniae and Nontypable Haemophilus influenzae in Children: The Impact of Vaccination

BACKGROUND Protracted bacterial bronchitis is a major cause of persistent cough in childhood. The organisms most commonly isolated are nontypable Haemophilus influenzae and Streptococcus pneumoniae . There are no studies addressing typing of these organisms when recovered from the lower airways. METHODS Isolates of these two organisms (identified in BAL samples from children undergoing routine investigation of a chronic cough thought to be attributable to a protracted bacterial bronchitis) were subject to typing. Samples were collected in Sheffield, England, and Athens, Greece. The majority of the children from Sheffield had received pneumococcal-conjugate vaccines 7 or 13 (PCV-7 or PCV-13) conjugate vaccine but only a minority of Greek children had received PCV-7. RESULTS All 18 S pneumoniae isolates from Greek BAL samples are serotypes contained in PCV-13 while 10 are contained in PCV-7. In contrast, 28 of the 39 samples from Sheffield contained serotypes that are not included in PCV-13. All 26 of the nontypable H influenzae samples obtained in Sheffield produced distinct multilocus variable-number tandem repeat analysis profiles. There was a significant difference between children from Athens and Sheffield in the distribution of serotypes contained or not contained in the pneumococcal vaccine ( P = .04). More specifically, immunization with pneumococcal vaccine was related with isolation of S pneumoniae serotypes not included in the vaccine (OR, 0.021; CI, 0.003-0.115; P < .001). CONCLUSIONS The data suggest that both vaccine and nonvaccine S pneumoniae serotypes may play a role in protracted bacterial bronchitis and provide some hints that serotype replacement may occur in response to the introduction of conjugate vaccines.

Seven-Year Surveillance of emm Types of Pediatric Group A Streptococcal Pharyngitis Isolates in Western Greece

Background An experimental 26-valent M protein Group A streptococcal (GAS) vaccine has entered clinical studies. Pharyngeal GAS emm type surveillances in different areas and time-periods enhance the understanding of the epidemiology of GAS pharyngitis. Moreover, these surveillances, combined with the data on GAS invasive disease, can play a significant role in the formulation of multivalent type-specific vaccines. Methods During a 7-year period (1999–2005), 2408 GAS isolates were recovered from consecutive children with pharyngitis in Western Greece. The overall macrolide resistance rate was 22.8%. Along the study period we noted a tendency towards significantly decreased rates of resistance, with the lowest rates occurring in 2002 (15.3%), 2003 (15%) and 2004 (16.7%). A random sample of isolates from each year, 338 (61.7%) of the 548 macrolide-resistant and 205 (11%) of the macrolide-susceptible, underwent molecular analysis, including emm typing. Results The 543 typed isolates had 28 different emm types. A statistically significant association was found between macrolide resistance and emm4, emm22 and emm77, whereas emm1, emm3, emm6, emm12, emm87 and emm89 were associated with macrolide susceptibility. A significant yearly fluctuation was observed in emm4, emm28 and emm77. The most common macrolide-resistant GAS were emm77 isolates harboring erm(A), either alone or in combination with mef(A), emm4 carrying mef(A), emm28 possessing erm(B), emm75 carrying mef(A), emm12 harboring mef(A) and emm22 carrying erm(A). We estimated that 82.8% of the isolates belonged to emm types included in the novel 26-valent M protein vaccine. The vaccine coverage rate was determined mainly by the increased frequency of nonvaccine emm4 isolates. Conclusions A limited number of emm types dominated among macrolide-susceptible and macrolide-resistant GAS isolates. We observed seasonal fluctuations, which were significant for emm4, emm28 and emm77. This type of data can serve as baseline information if the novel 26-valent M protein GAS vaccine is introduced into practice.

Black hairy tongue in a 2‐month‐old infant

Abstract:  Black hairy tongue (BHT) is an unusual condition in adults, and is characterised by marked accumulation of keratin on the filiform papillae of the dorsum of the tongue resulting in a hairlike appearance. The colour of the papillae may vary from brown to black. We describe a case of BHT in a 2‐month‐old infant. An extended review of the literature suggests that our case is the youngest ever reported. In conclusion, although BHT is considered benign, clinical, haematological and histological, evaluation is recommended to exclude several entities which can present as pigmented lesions of the oral mucosa.

European ST80 community-associated methicillin-resistant Staphylococcus aureus orbital cellulitis in a neonate

BackgroundMethicillin-resistant Staphylococcus aureus is a serious cause of morbidity and mortality in hospital environment, but also, lately, in the community. This case report is, to our knowledge, the first detailed description of a community-associated methicillin-resistant S. aureus ST80 orbital cellulitis in a previously healthy neonate. Possible predisposing factors of microbial acquisition and treatment selection are also discussed.Case presentationA 28-day-old Caucasian boy was referred to our hospital with the diagnosis of right orbital cellulitis. His symptoms included right eye proptosis, periocular edema and redness. Empirical therapy of intravenous daptomycin, rifampin and ceftriaxone was initiated. The culture of pus yielded a methicillin-resistant S. aureus isolate and the molecular analysis revealed that it was a Panton-Valentine leukocidine-positive ST80 strain. The combination antimicrobial therapy was continued for 42 days and the infection was successfully controlled.ConclusionsClinicians should be aware that young infants, even without any predisposing condition, are susceptible to orbital cellulitis caused by community-associated methicillin-resistant S. aureus. Prompt initiation of the appropriate empirical therapy, according to the local epidemiology, should successfully address the infection, preventing ocular and systemic complications.

Macrolide resistance determinants among Streptococcus pneumoniae isolates from carriers in Central Greece

BackgroundWe sought to characterize the temporal trends in nasopharyngeal carriage of macrolide-resistant pneumococci during a period with increased heptavalent pneumococcal conjugate vaccine (PCV7) coverage in Central Greece.MethodsStreptococcus pneumoniae isolates were recovered from 2649 nasopharyngeal samples obtained from day-care center attendees in Central Greece during 2005–2009. A phenotypic and genotypic analysis of the isolates was performed, including the identification of macrolide resistance genes mef(A), subclasses mef(A) and mef(E), as well as erm(B).ResultsOf the 1105 typeable S. pneumoniae isolates, 265 (24%) were macrolide-resistant; 22% in 2005, 33.3% in 2006, 23.7% in 2007, and 20.5% in 2009 (P=0.398). Among these macrolide-resistant pneumococci, 28.5% possessed erm(B), 24.3% erm(B)+mef(E), 41.8% mef(E), and 5.3% mef(A). A mef gene as the sole resistance determinant was carried by 31% of macrolide-resistant isolates belonging to PCV7 serotypes and 75.8% of the non-PCV7 serotypes. Across the 4 annual surveillances, pneumococci carrying mef(A) gradually disappeared, whereas serotype 19F isolates carrying both erm(B) and mef(E) persisted without significant yearly fluctuations. Among isolates belonging to non-PCV7 serotypes, macrolide-resistance was observed in those of serotypes 6A, 19A, 10A, 15A, 15B/C, 35F, 35A, and 24F. In 2009, ie 5 years after the introduction of PCV7 in our country, 59% of macrolide-resistant pneumococci belonged to non-PCV7 serotypes.ConclusionsAcross the study period, the annual frequency of macrolide-resistant isolates did not change significantly, but in 2009 a marked shift to non-PCV7 serotypes occurred. Overall, more than half of the macrolide-resistant isolates possessed erm(B) either alone or in combination with mef(E). erm(B) dominated among isolates belonging to PCV7 serotypes, but not among those of non-PCV7 serotypes.