Penicillin-resistant Pneumococci Research Articles

A Review of the Impact of Streptococcal Infections and Antimicrobial Resistance on Human Health.

Streptococcus pneumoniae, Streptococcus pyogenes (GAS), and Streptococcus agalactiae (GBS) are bacteria that can cause a range of infections, some of them life-threatening. This review examines the spread of antibiotic resistance and its mechanisms against antibiotics for streptococcal infections. Data on high-level penicillin-resistant invasive pneumococci have been found in Brazil (42.8%) and Japan (77%). The resistance is caused by mutations in genes that encode penicillin-binding proteins. Similarly, GAS and GBS strains reported from Asia, the USA, and Africa have undergone similar transformations in PBPs. Resistance to major alternatives of penicillins, macrolides, and lincosamides has become widespread among pneumococci and streptococci, especially in Asia (70-95%). The combination of several emm types with erm(B) is associated with the development of high-level macrolide resistance in GAS. Major mechanisms are ribosomal target modifications encoded by erm genes, ribosomal alterations, and active efflux pumps that regulate antibiotic entry due to mefA/E and msrD genes. Tetracycline resistance for streptococci in different countries varied from 22.4% in the USA to 83.7/100% in China, due to tet genes. Combined tetracycline/macrolide resistance is usually linked with the insertion of ermB into the transposon carrying tetM. New quinolone resistance is increasing by between 11.5 and 47.9% in Asia and Europe. The mechanism of quinolone resistance is based on mutations in gyrA/B, determinants for DNA gyrase, or parC/E encoding topoisomerase IV. The results for antibiotic resistance are alarming, and urgently call for increased monitoring of this problem and precautionary measures for control to prevent the spread of resistant mutant strains.

Delayed Administration of Recombinant Plasma Gelsolin Improves Survival in a Murine Model of Penicillin-Susceptible and Penicillin-Resistant Pneumococcal Pneumonia.

Therapy to enhance host immune defenses may improve outcomes in serious infections, especially for antibiotic-resistant pathogens. Recombinant human plasma gelsolin (rhu-pGSN), a normally circulating protein, has beneficial effects in diverse preclinical models of inflammation and injury. We evaluated delayed therapy (24-48 hours after challenge) with rhu-pGSN in a mouse model of pneumococcal pneumonia. rhu-pGSN without antibiotics increased survival and reduced morbidity and weight loss after infection with either penicillin-susceptible or penicillin-resistant pneumococci (serotypes 3 and 14, respectively). rhu-pGSN improves outcomes in a highly lethal pneumococcal pneumonia model when given after a clinically relevant delay, even in the setting of antimicrobial resistance.

The Emergence of Antimicrobial Resistance as a Public Matter of Concern: A Swedish History of a "Transformative Event".

ArgumentThis article examines how antimicrobial resistance (AMR) came to be constituted as a matter of public concern in Sweden in conjunction with the development of an inter-professional organization called Strama, founded to promote rational prescription of antibiotics. An outbreak of penicillin-resistant pneumococci in the mid-1990s was crucial for this development, because it brought attention to AMR as an urgent public threat. This outbreak fuelled the constitution of AMR as caused by consumption of antibiotics and as a matter of disease control. As a consequence, Strama was able to mobilize the Swedish health officers responsible for disease control. The outbreak is conceptualized as a "transformative event" - an event that makes an issue and its associated risks concrete and urgent. Transformative events play the crucial role of expediting the transformation of issues into matters of public concern.

2401. Risk Factors for Antimicrobial Resistance in Invasive Pneumococcal disease (IPD) in Toronto, Canada, 2012–2017

BackgroundSeveral studies have documented factors predictive of antimicrobial resistance (AMR) in invasive pneumococcal disease(IPD). However, the implementation of routine pediatric PCV programs, antimicrobial stewardship, and increasing immunocompromised in populating might be expected to change such factors. We report on predictive factors for AMR in IPD from 2012 to 2017.MethodsTIBDN performs population-based surveillance for IPD in Toronto/Peel (pop 4.5M). IPD cases are reported to a central office and one isolate/case is serotyped and has antimicrobial susceptibility testing performed by broth microdilution to CLSI standards.Results2459 cases of IPD were identified from January 2012 to December 2017. Overall rates of resistance to penicillin, macrolides, fluoroquinolones, and TMP-SMX were relatively stable over the course were stable over the study. Risk factors for infection with resistant to penicillin at meningitis breakpoints as opposed to penicillin- susceptible pneumococci were current residence at nursing home (odds ratio [OR], 2.30; P < 0.001), immune compromised status (OR, 1.41; P = 0.012), HIV infection (OR 2.13, P = 0.016), history of receiving PPV23 vaccine (OR 1.38; P = 0.007). Infection with TMP-SMX-resistant pneumococci was associated with HIV infection (OR, 3.2; P = 0.001) and current residence in a nursing home (OR 2.4, P = 0.002). Infection with macrolide-resistant isolates was associated with any use of macrolide 3 months prior to infection (OR, 3.24; P < 0.001), or macrolide treatment failure of the current episode (OR, 6.64; P = 0.003). Infection with levofloxacin-resistant pneumococci was associated with current residence in a nursing home (OR, 13.7; P < .001), and fluorquinolone treatment failure of the current episode (OR 49.4, P = 0.0034).ConclusionPrevious same class antibiotic exposure remains a major predictive factor for macrolide resistance. History of treatment failure is a predictive factor for macrolide and fluoroquinolone failure. HIV infection and immune compromise are risk factors for IPD infection with penicillin resistant pneumococci. Hospital acquisition of infection is no longer a risk factor for fluoroquinolone resistance.Disclosures All authors: No reported disclosures.

Occurrence of linezolid induced thrombocytopenia and its association with the risk factors: a review article

Linezolid is the oxazolidinone group of antibiotic with wide range of activity against the gram positive bacteria including methicillin resistant staphylococcus aureus and penicillin resistant pneumococci and vancomycin resistant enterococci. Patients who are on linezolid were reported to have reversible myelosuppression especially thrombocytopenia and anaemia. Since there are less number of studies regarding the occurrence of thrombocytopenia and the risk factors associated with it, this study was undertaken to evaluate the occurrence of linezolid induced thrombocytopenia and its association with risk factors. It was a systematic review with synthesis of available literature in English language. Articles were retrieved using search terms included “linezolid”, “and”, “or”, “thrombocytopenia” from Clinical key and PubMed, published during 2000 - 2017. Out of 16 studies retrieved, only 7 studies were analysed based on inclusion and exclusion criteria; of them, 3 were found to be prospective and retrospective cohort each and only one was retrospective cross-sectional study. The occurrence of linezolid induced thrombocytopenia range from 18-50% with normal renal function and 57% of incidence associated with renal insufficiency patients. The risk factors were found to be dose of linezolid &gt;18-27mg/kg, body weight of subjects &lt;55kg, creatinine clearance &lt;88.39 to 60ml/min/1.73m2 and baseline platelet count &lt;200*103/mm3, serum albumin concentration, serum creatinine, concomitant caspofungin therapy and duration of linezolid therapy.

Impact of pneumococcal conjugate vaccines introduction on antibiotic resistance of Streptococcus pneumoniae meningitis in children aged 5 years or younger, Israel, 2004 to 2016.

BackgroundEmpiric treatment of pneumococcal meningitis includes ceftriaxone with vancomycin to overcome ceftriaxone resistant disease. The addition of vancomycin bears a risk of adverse events, including increased antibiotic resistance. We assessed antibiotic resistance rates in pneumococcal meningitis before and after pneumococcal conjugate vaccine (PCV) implementation. MethodsAll pneumococcal meningitis episodes in children aged 5 years and younger, from 2004 to 2016, were extracted from the nationwide bacteremia and meningitis surveillance database. For comparison purposes, we defined pre-PCV period as 2004–2008 and PCV13 period as 2014–2016. Minimal inhibitory concentration (MIC) > 0.06 and > 0.5 μg/mL were defined as penicillin and ceftriaxone resistance, respectively. ResultsOverall, 325 episodes were identified. Pneumococcal meningitis incidence rates declined non-significantly by 17%, comparing PCV13 and pre-PCV periods. Throughout the study, 90% of isolates were tested for antibiotic susceptibility, with 26.6%, 2.1% and 0% of isolates resistant to penicillin, ceftriaxone and vancomycin, respectively. Mean proportions (± SD) of meningitis caused by penicillin-resistant pneumococci were 40.5% ± 8.0% and 9.6% ± 7.4% in the pre-PCV and the PCV13 periods, respectively, resulting in an overall 83.9% reduction (odd ratio:0.161; 95% confidence interval: 0.059–0.441) in penicillin resistance rates. The proportions of meningitis caused by ceftriaxone resistant pneumococci were 5.0% ± 0.8% in the pre-PCV period, but no ceftriaxone resistant isolates were identified since 2010. ConclusionsPCV7/PCV13 sequential introduction resulted in > 80% reduction of penicillin- resistant pneumococcal meningitis and complete disappearance of ceftriaxone resistant disease. These trends should be considered by the treating physician when choosing an empiric treatment for pneumococcal meningitis.

Aetiology of lower respiratory tract infection in adults in primary care: a prospective study in 11 European countries

ObjectivesTo describe the role of bacteria (including bacterial resistance), viruses (including those recently described) and mixed bacterial–viral infections in adults presenting to primary care with lower respiratory tract infection (LRTI). MethodsIn all, 3104 adults with LRTI were enrolled, of whom 141 (4.5%) had community-acquired pneumonia (CAP), and 2985 matched controls in a prospective study in 16 primary care networks in Europe, and followed patients up at 28–35 days. We detected Streptococcus pneumoniae and Haemophilus influenzae and assessed susceptibility, atypical bacteria and viruses. ResultsA potential pathogen was detected in 1844 (59%) (in 350 (11%) bacterial pathogens only, in 1190 (38%) viral pathogens only, and in 304 (10%) both bacterial and viral pathogens). The most common bacterial pathogens isolated were S. pneumoniae (5.5% overall, 9.2% in CAP patients) and H. influenzae (5.4% overall, 14.2% in CAP patients). Less than 1% of S. pneumoniae were highly resistant to penicillin and 12.6% of H. influenzae were β-lactamase positive. The most common viral pathogens detected were human rhinovirus (20.1%), influenza viruses (9.9%), and human coronavirus (7.4%). Influenza virus, human parainfluenza viruses and human respiratory syncytial virus as well as human rhinovirus, human coronavirus and human metapneumovirus were detected significantly more frequently in LRTI patients than in controls. ConclusionsA bacterial pathogen is identified in approximately one in five adult patients with LRTI in primary care, and a viral pathogen in just under half, with mixed infections in one in ten. Penicillin-resistant pneumococci and β-lactamase-producing H. influenzae are uncommon. These new findings support a restrictive approach to antibiotic prescribing for LRTI and the use of first-line, narrow-spectrum agents in primary care.

Risk of ceftriaxone-associated pseudolithiasis during therapy for bacterial meningitis

Background: Ceftriaxone (CTRX) is frequently administered to treat bacterial meningitis because it has broad antibacterial activity, including against penicillin-resistant pneumococcus. In Japan, the CTRX therapeutic dose for bacterial meningitis is 4 g/day—higher than for infections of other organs. CTRX-associated pseudolithiasis has been reported as a rare side effect.

Longitudinal survey of ATB resistance reversibility in children with AIDS of genocide survivors in Cambodia

Background: The aim of the survey was to assess antimicrobial resistance dynamics and reversibility in the group of children with AIDS in Cambodia in 2003 2015. Patients: Correlation between antimicrobial (ATB) resistances in commonest respiratory isolates among 140 children with AIDS on antiretroviral therapy was studied from 2003 to 2015 in 586 isolates. Original Articles 8 Clinical Social Work and Health Intervention Clinical Social Work and Health Intervention Vol. 7 No. 3 2016 Results: All but 3 (98%) children showed a sustained CD4 increase after introduction of antiretroviral therapy (ART) followed by a decrease of ATB resistance. In our group of children restoration of the immune system decreased the number of infection diseases episodes and the proportion of multi-resistant bacterial strains. Conclusions: Less frequent use of antimicrobial therapy probably led to the decrease of multi-resistance and restoration of susceptibility of studied respiratory bacterial isolates. Results and discussion Table 1 presents trends in ATB resistance in major respiratory isolates from October 2003 to December 2015 (total of 586 isolates). Penicillin resistance in pneumococci decreased from 25% to 2% in 2015 (P<0.01); t-test for trends), MRSA from 33.3% in 2003 to 3% in 2014 and 2% in 2015 (P<0.01). Erythromycin resistance in Streptococcus pyogenes decreased from 10.5% in 2003 to 3.3% in 2015. At baseline extremely high proportion of ESBL producing Enterobacteriaceae decreased from 66.6% to 25% and such trend was also observed in Candida species and resistance to fluconazole (from 15% in 2003 to 6% in 2015). Reversibility of ATB resistance was documented on the hospital level (2) or on the community national level (1.3), however only in countries with small population (Finland, Denmark, Iceland) with centralized ATB policy. Reversibility time was 2-5 years per country and more (up to 5 years). Reversibility of susceptibility or antibiotic resistance was not yet sufficiently studied in pediatric population with specific immunodeficiency therefore it is deficient to assess, of 10 15 years in our group is comparable to e.g. 2 5 years on a nation level from Europe (5-8).

Are migrants from Middle East carriers of multi-resistant bacteria?

Background: In 2015 about 1.2 million migrants via the Balkan Route (Greece to Austria and Germany) and about 250,000 migrants via the Sicily (Lampedusa) Malta Route entered the EU. Patients: Among 544,310 migrants in our field hospitals and checkpoints (Austria, Slovenia, and Greece) from Sept. 2015 to June 2016, Original Articles 11 Clinical Social Work and Health Intervention Clinical Social Work and Health Intervention Vol. 7 No. 3 2016 Introduction Discovery of the NDM-1 “travel” from India to Sweden, or MCR-1 genes coding colistin resistance from China to Europe are examples how multi-resistant bacteria from the 3rd World may enter EU countries, even with strict ATB policy specially via conflict areas or migration (1.2). Middle East and Southeast Asia are leading areas of the last large refugee event (Balkan and Mediterranean Route) whereas 1.351.5 million migrants and or refugees crossed the Greek or Italian Mediterranean border in 2015 (3-4). The aim of this short communication is to assess the risk of transfer or MR bacteria (5) within migrants in 2015/2016 from Middle East/Near East countries to the EU and dissolve the fear that refugees/migrants must be necessary carriers (6) of multi-resistant microbes or deadly diseases (6-9). Patients and Methods 12 Healthcare Workers (HCW) have been serving at the Nickelsdorf/Hegyeshalom (AT/ HU) and Dobova/Rigonce (CRO/SL) on 8 hour shifts, serving for 2 16,000 migrants per day. The Health Posts and Field Hospital on Austrian, Hungarian, Slovenia borders were opened since September 6, 2015 to March 2, 2016. In the six month period (9/2015 2/2016) about 319,500 migrants and or refugees crossed our Healthcare units, most, 90% of them healthy or not seeking medical care. About 29,500 (5,000 per month, 150 200 per day) presented themselves to one of our new facilities requiring healthcare and or therapy. Results and Discussion Concerning the spectrum of migrants 68% were from Syria, 21% from Iraq and 11% from other Asian countries. (Afghanistan, Pakistan). Table1 shows the commonest diagnoses. The majority had surprisingly little tropical, but “civilization” and “stress related” diseases, such as hypertension, coronary heart disease, neurovascular; diseases include decomposed diabetes, asthma, depression, etc., and camping related disorders (pneumonia, infected wounds, etc.). Only about 10% were infections, similar to those we can see in Central/Eastern EU members states Hungary and Slovakia. From 528 cases of lower respiratory tract infections (L-RTI), we obtained swabs from the oropharynx and nose and in 101 samples pathogenic yeasts or bacteria (Tab1.) we isolated. Antibiotic resistance was minimal and did not show any major threat to the host population. Only 1 penicillin-resistant Pneumococcus, 4 methicillin-resistant Staphylococcus aureus (MRSA) and 1 multidrug-resistant (MDR) gram-negative bacteria (Klebsiella spp., resistant to all antibiotics including colistin (Table 1) were isolated. All Candida albicans are susceptible to fluconazole (FLU) but 3 of 7 non-albicans Candida spp (C. tropicalis, C. glabrata, C. krusei etc.) were FLU resistant. Surprisingly all H. influenzae strains are susceptible to ampicillin and all S. pyogenes were susceptible to erytromycin. bacterial isolates from patients with respiratory symptoms were obtained and 209 isolates were tested with available antibiotics. Results: Only 4 Methicillin Resistant Staphylococcus aureus MRSA (4%) and 1 Penicillin Resistant Pneumococcus PRP we isolated from migrants with symptomatic respiratory infections. Conclusions: Our small research compared to our expectations did not find any major resistance patterns colonizing or infecting migrants coming to the EU via the Balkan route from Syria, Iraq via Greece to Austria and Germany. 12 Original Articles Clinical Social Work and Health Intervention Vol. 7 No. 3 2016 Conclusion In conclusion, despite the increasing number of migrants and or refugees via the „Balkan Route“, in contrast to those who are coming via Italy and Malta, our research found only a small proportion (1-4%) of multi-resistant bacterial isolates from the respiratory tract among our group of predominantly Syrian and Iraqi migrants.

Clinical and microbiological implications of invasive pneumococcal disease in hospitalized patients (1998–2013)

IntroductionInfections caused by Streptococcus pneumoniae (pneumococcus) still represent a challenge for health systems around the world. ObjectiveThe objective of this study was to assess microbiological and clinical aspects in hospitalized patients with invasive pneumococcus disease between 1998 and 2013. Materials and methodsThis was a retrospective study that analyzed the results of pneumococcus identification, serotyping, and susceptibility testing found in the Adolfo Lutz Institute databank. Personal variables, medical history and clinical outcome of patients admitted with invasive pneumococcal disease were analyzed. These were obtained from records of a public teaching hospital – Hospital das Clínicas Faculdade de Medicina Ribeirão Preto. ResultsThe sample comprised 332 patients. Patient age ranged from less than one month to 89 years old (mean 20.3 years) and the sample was predominately male. Pneumonia (67.8%) was the most common disease, accounting for 18.2% of deaths. Serotypes 14, 1, 3, 9V, 6B, 6A, 23F, 19A, 18C, 19F, 12F, and 4 were the most common (75.3%). Most patients, or 67.5%, were cured without any complication (success), 6.9% had some type of sequela (failure), and 25.6% died (failure). In the case of deaths due to meningitis, strains of fully penicillin resistant pneumococcus were isolated. Furthermore, 68.2% of patients who died presented some type of comorbidity. The 60 and older age group presented the most significant association (Odds Ratio=4.2), with outcome failure regardless of the presence of comorbidity. Serotype 18C was the most significant risk factor both in raw analysis (Odds Ratio=3.8) and when adjusted for comorbidity (Odds Ratio=5.0) or age (Odds Ratio=5.4). The same occurred with serotype 12F (respectively, Odds Ratio=5.1, Odds Ratio=5.0, and Odds Ratio=4.7) ConclusionThe present findings highlight the importance of IPD among young adults and older adults. In the era of conjugate vaccines, monitoring serotypes in different age groups is essential to assess the impact and adequacy of immunization.

Ceftobiprole medocaril in the treatment of hospital-acquired pneumonia.

Ceftobiprole medocaril is a fifth-generation cephalosporin approved in Europe as single-agent therapy for hospital-acquired pneumonia (HAP), excluding ventilator-associated pneumonia (VAP). It is rapidly converted to the active metabolite ceftobiprole following intravenous administration. Ceftobiprole has a broad spectrum of activity, notably against methicillin-resistant Staphylococcus aureus, ampicillin-susceptible enterococci, penicillin-resistant pneumococci and Enterobacteriaceae not producing extended-spectrum β-lactamase. Ceftobiprole is primarily excreted renally by glomerular filtration, with minimal propensity for interaction with co-administered drugs. Normal dose is ceftobiprole 500 mg, administered by 2-h intravenous infusion every 8 h, with dose adjustment according to renal function. In a pivotal Phase III trial in patients with HAP, ceftobiprole monotherapy was as efficacious as ceftazidime/linezolid for clinical and microbiological cure and was noninferior to ceftazidime/linezolid in the subgroup of patients with HAP excluding VAP. Ceftobiprole and ceftazidime/linezolid were similarly well tolerated. Ceftobiprole is an efficacious and well-tolerated option for empirical treatment of patients with HAP (excluding VAP).

Peculiar hyper-IgM syndrome. Case report / Sindrom hiper-IgM atipic. Prezentare de caz

Abstract We report a male infant diagnosed at the age of 10 months with hyper-IgM syndrome (HIGM) in context of severe infections caused by Streptococcus pneumoniae, Staphylococcus aureus and Candida albicans. In patient’s outcome, in spite of immunoglobulin therapy, he continues presenting bilateral suppurative otitis media due to both Candida and penicillin-resistant pneumococcus and forearm abscess caused by Staphylococcus aureus. The infant developed bilateral cataracts, chronic hepatitis and comminuted fracture secondary to bone demineralization. The patient didn’t develop opportunistic infections as compare to CD40 Ligand deficiency patients. In contrast with the majority of HIGM cases, the infant necessity for immunoglobulin substitution was very limited. As a particularity of immunological phenotype, the patient IgM value progressively increased at a high level.

Want a better way to control antibiotic resistance? Fight the corruption

Want a better way to control antibiotic resistance? Fight the corruption

Increasing penicillin resistance in pneumococci isolated from cerebrospinal fluid samples: Fifteen-year experience from a teaching hospital

Objective: There have been prominent changes in evaluation of resistance patterns of pneumococci and breakpoint values in recent years. We aimed to investigate the penicillin sensitivity of pneumococcal strains isolated from the cesrebrospinal fluid specimens between the years 1997-2011 in our hospital and determine the MIC values under the light of these changes. Methods: Identification of pneumococci was made with conventional methods in patients with meningitis. MIC values for penicillin G were investigated by E test method in all strains. MIC values of pneumococci strains were evaluated acscording to values determined by CLSI for meningitis isolates in 2008. Results: A total of 57 strains were investigated in this study. The MIC range for penicillin was 0.016 - 0.75 mg/ml in S. pneumoniae strains. Seventy five percent of the strains were sensitive and eight strains (14%) had resistance. MIC50 value was sensitive, and a MIC90 value was resistant. The first resistant strain was detected in 2000, and three strains were resistant in the last year. When examined over the years increased resistance was 5.3% in the first five-year period seems to be 28.6% in the last five-year period. Conclusions: Knowledge on penicillin resistance patterns and surveillance is very important in the empirical treatment in pneumococcal meningitis.

Ceftaroline activity against organisms isolated from respiratory tract infections in USA hospitals: results from the AWARE program, 2009–2011

The Assessing Worldwide Antimicrobial Resistance Evaluation Program monitors the activity of ceftaroline and comparator agents tested against pathogens causing either respiratory or skin and soft tissue infections. A total of 7733 isolates from patients in 80 medical centers across the United States (USA) identified as respiratory tract pathogens by the infection type and/or specimen site recorded by the submitting laboratory during 2009–2011 were evaluated. There were 3360 isolates of Streptococcus pneumoniae, 1799 Haemophilus influenzae, 1087 Staphylococcus aureus, 678 Moraxella catarrhalis, 459 Klebsiella pneumoniae, 223 Escherichia coli, and 127 Klebsiella oxytoca. Annual penicillin resistance among S. pneumoniae ranged from 21.9 to 24.3%. All S. pneumoniae strains were inhibited at a ceftaroline MIC of ≤0.5 μg/mL with 100.0% of isolates categorized as susceptible. Ceftaroline was 16-fold more active than ceftriaxone and 32-fold more active than amoxicillin-clavulanate against penicillin-resistant pneumococci. Only 49.8% of the penicillin-resistant isolates were susceptible to ceftriaxone. There were a total of 1087 S. aureus (48.9% methicillin-resistant S. aureus [MRSA]) isolates, and the yearly MRSA rate ranged from 47.9 to 49.7%. The ceftaroline MIC50/90 for S. aureus was at 0.25/1 μg/mL; 98.2% susceptible and no resistant strains (≥4 μg/mL). Ceftaroline activity against methicillin-susceptible S. aureus (MSSA) isolates (MIC50 and MIC90, 0.25 and 0.25 μg/mL, respectively; 100% susceptible) was 2- to 4-fold greater than for MRSA (MIC50/90, 0.5/1 μg/mL; 96.2% susceptible). The ceftriaxone MIC90 for MSSA was 4 μg/mL. Ceftaroline was active against H. influenzae (MIC50/90 ≤0.015/0.03 μg/mL; 100.0% susceptible) and against M. catarrhalis (MIC50/90, 0.06/0.12 μg/mL). Ceftaroline was active against non–extended spectrum β-lactamase (ESBL) phenotype strains of Enterobacteriaceae but not against ESBL-positive phenotype strains. In summary, ceftaroline was highly active against a large collection of bacterial pathogens isolated from patients with respiratory tract infections in the USA during 2009 through 2011.

Mortality indicators in pneumococcal meningitis: therapeutic implications

The aim of this study was to delineate mortality indicators in pneumococcal meningitis with special emphasis on therapeutic implications. This retrospective, multicenter cohort study involved a 15-year period (1998-2012). Culture-positive cases (n=306) were included solely from 38 centers. Fifty-eight patients received ceftriaxone plus vancomycin empirically. The rest were given a third-generation cephalosporin alone. Overall, 246 (79.1%) isolates were found to be penicillin-susceptible, 38 (12.2%) strains were penicillin-resistant, and 22 (7.1%) were oxacillin-resistant (without further minimum inhibitory concentration testing for penicillin). Being a critical case (odds ratio (OR) 7.089, 95% confidence interval (CI) 3.230-15.557) and age over 50 years (OR 3.908, 95% CI 1.820-8.390) were independent predictors of mortality, while infection with a penicillin-susceptible isolate (OR 0.441, 95% CI 0.195-0.996) was found to be protective. Empirical vancomycin use did not provide significant benefit (OR 2.159, 95% CI 0.949-4.912). Ceftriaxone alone is not adequate in the management of pneumococcal meningitis due to penicillin-resistant pneumococci, which is a major concern worldwide. Although vancomycin showed a trend towards improving the prognosis of pneumococcal meningitis, significant correlation in statistical terms could not be established in this study. Thus, further studies are needed for the optimization of pneumococcal meningitis treatment.

English

INTRODUCTION: S.pneumoniae is the major cause of morbidity and mortality in India and abroad and carriage is the key to invasive disease. Carriage (20-60%) and invasive disease are more prevalent in children and in the elderly. Increased case fatality is due to the emergence of Penicillin and Multidrug Resistant S.pneumoniae worldwide. Penicillin has been the drug of choice for treatment of pneumococcal infections but the increasing number of reports of penicillin resistant pneumococci (PRP) throughout the world makes it essential to regionally determine the prevalence of PRP. MATERIALS AND METHODS: Nasopharyngeal swabs were collected from children between ≥ 3 months and ≤ 5 years of age attending paediatric immunization OPD in a medical college tertiary care hospital and research centre, Bengaluru, between December 2008 and August 2009 ( 8 months). S. pneumoniae were isolated based on colony morphology, Gram's staining, optochin sensitivity, and bile solubility. Antimicrobial susceptibility testing was carried out by Kriby-Bauer disc diffusion method for recommended commonly prescribed antibiotics. Oxacillin resistant strains denoting penicillin resistance were tested for Minimum inhibitory concentration for Penicillin G by Epsilometer test. RESULTS: 53 (27.89 %) S. pneumoniae were isolated from 190 nasopharyngeal swabs. 9 (16.98%) isolates have been intermediately penicillin resistant by E test. Only 5 (9.43%) and 34 (64.15%) isolates were sensitive to co-trimoxazole and tetracycline respectively. 51 isolates were susceptible to cefotaxime, 48 (90.56%) each were susceptible to erythromycin and ciprofloxacin. 25(47.19%) out of 53 isolates could be recovered at the end of one year stored in STGG medium at -20˚ C. Serogroup types 19, 10, 3, 14, 7, were common among the isolates. CONCLUSION: Carriage of S. pneumoniae is prevalent among young children in Bengaluru, which may predispose them to subsequent invasive pneumococcal diseases. There is decreased susceptibility to penicillin and other recommended antibiotics that may warrant appropriate culture and sensitivity testing during the management of invasive pneumococcal diseases and prescription of antibiotics in general.

Nasopharyngeal carriage rate of Streptococcus pneumoniae in Ugandan children with sickle cell disease

BackgroundNasopharyngeal carriage of Streptococcus pneumoniae is a determinant for invasive pneumococcal disease, which often complicates homozygous sickle cell disease. Here, we determined the nasopharyngeal carriage rate of S. pneumoniae in Ugandan children with homozygous sickle cell disease, who attended the outpatient Sickle Cell Clinic at Mulago National Referral hospital in Kampala, Uganda.ResultsS. pneumoniae occurred in 27 of the 81 children with homozygous sickle cell disease (giving a carriage rate of 33%, 27/81). Twenty three children were previously hospitalized of whom S. pneumoniae occurred in only two (9%, 2/23), while among the 58 who were not previously hospitalized it occurred in 25 (43%, 25/58, χ2 = 8.8, p = 0.003), meaning there is an association between high carriage rate and no hospitalization. Two children previously immunized with the pneumococcal conjugate vaccine did not carry the organism. Prior antimicrobial usage was reported in 53 children (65%, 53/81). There was high resistance of pneumococci to penicillin (100%, 27/27) and trimethoprime-sulfamethoxazole (97%, 26/27), but low resistance to other antimicrobials. Of the 70 children without sickle cell disease, S. pneumoniae occurred in 38 (54%, 38/70) of whom 43 were males and 27 females (53% males, 23/43, and 56% females, 15/27).ConclusionNasopharyngeal carriage of penicillin resistant pneumococci in Ugandan children with homozygous sickle cell disease is high. While nasopharyngeal carriage of S. pneumoniae is a determinant for invasive pneumococcal disease, pneumococcal bacteremia is reportedly low in Ugandan children with sickle cell disease. Studies on the contribution of high carriage rates to invasive pneumococcal disease in these children will be helpful. This is the first report on pneumococcal carriage rate in Ugandan children with sickle cell disease.

Is adjunctive corticosteroid beneficial in pneumococcal meningitis in a region with high rates of resistance to penicillin and ceftriaxone?

The role of adjunctive corticosteroids remains controversial in meningitis by penicillin-resistant pneumococci. We determined the effect of adjunctive corticosteroids in adults with pneumococcal meningitis in a region with a high rate of penicillin resistance. A multicenter, retrospective cohort study was conducted between 1998 and 2008 in Korea. The mortality and neurological sequelae were evaluated. Among 93 patients with pneumococcal meningitis, adequate adjunctive corticosteroids were given in 45.2%. The penicillin resistance rate was 60.0%, and 42.1% were nonsusceptible to ceftriaxone. The 30-day mortality rates in the group receiving adequate corticosteroid therapy, the group in which corticosteroid was not given, and that inadequately given were 24.3, 31.6, and 27.3%, respectively, and there was no difference between the groups. The rates of development of neurological sequelae were 34.3, 33.3, and 43.5%, respectively. Multivariate analysis showed that adequate corticosteroids did not reduce mortality (HR 0.773, 95% CI 0.293-2.040) and neurologic sequelae (HR 0.604, CI 0.262-1.393). Propensity-adjusted analysis showed that adjunctive corticosteroid was not associated with time to death (HR 0.949, CI 0.374-2.408), however, a decreasing tendency was shown in neurologic sequelae in the adequate corticosteroid group (HR 0.479, CI 0.207-1.110). In conclusion, adjunctive corticosteroids did not affect mortality in adults with pneumococcal meningitis in a region with high rates of resistance to penicillin and ceftriaxone; however, the patients receiving adequate corticosteroid therapy tended to develop neurologic sequelae less frequently.