The clinical outcomes of antimicrobial therapy in pediatric patients with nontyphoid salmonellosis with different levels of severity.

BACKGROUND: To evaluate if a severity score could differentiate the severity of children with nontyphoid salmonellosis; clinical outcomes of antimicrobial therapy in nontyphoid salmonellosis children with different severities. METHODS: Admitted children with nontyphoid salmonellosis from 1996 to 2009 were monitored. Enrolled patients were divided into no antibiotics, concordant, and discordant therapies. Besides, the patients were classified into mild, moderate, and severe group according to the severity score. Clinical outcomes were compared among them. RESULTS: A total of 558 patients were enrolled. In no therapy subset, compared with mild group, patients had worse clinical outcomes and more complications in severe group. Patients receiving no therapy had better clinical outcomes in mild group. However, patients receiving concordant therapy (ceftriaxone) had better clinical outcomes in severe group. CONCLUSIONS: The severity score and local antibiotic susceptibility could serve as guides for antibiotic prescription for severe nontyphoid salmonellosis in children. Inappropriate antibiotic use would worsen clinical outcomes in children with mild nontyphoid salmonellosis.

Clinical manifestations of nontyphoid salmonellosis in children younger than 2 years old--experiences of a tertiary hospital in southern Taiwan.

BACKGROUND: Few published studies have explored the clinical manifestations of nontyphoid salmonellosis in children <2 years of age. The aim of this study was to investigate the clinical manifestations, microbiological features, complications, fecal excretion time, and responses to treatment in children <2 years of age with nontyphoid salmonellosis. METHODS: Between January 2005 and December 2009, pediatric patients who were admitted to Kaohsiung Veterans General Hospital with positive cultures for nontyphoid Salmonella were enrolled. The following data were recorded: demographic, clinical, and microbiological features, underlying diseases, treatment regimen, complications, responses to treatment, and fecal excretion time. The clinical manifestations were compared between patients <2 years of age and patients >2 years of age. RESULTS: Of a total 279 enrolled patients, 179 were >2 years of age. Compared with the patients who were ≥2 years of age, patients <2 years of age demonstrated a significantly higher incidence of bloody stool, mixed infection, extraintestinal infection, longer course of antibiotics, longer course of diarrhea after admission, and more days spent in the hospital. The rates of insusceptibility of nontyphoid Salmonella to ampicillin, chloramphenicol, trimethoprim/sulfamethoxazole, ceftriaxone, and ciprofloxacin in patients <2 years of age were 37.87%, 29.09%, 23.73%, 3.26%, and 2.25%, respectively. Younger patients were generally more susceptible to antibiotics than patients ≥2 years of age, although this result was not statistically significant. CONCLUSION: The clinical manifestations of nontyphoid salmonellosis are more severe in younger children <2 years of age than older children. Local susceptibility patterns could serve as a guide for the prescription of antibiotics by clinicians.

Early administration of probiotic Lactobacillus acidophilus and/or prebiotic inulin attenuates pathogen-mediated intestinal inflammation and Smad 7 cell signaling.

Immaturity of gut-associated immunity may contribute to pediatric mortality associated with enteric infections. A murine model to parallel infantile enteric disease was used to determine the effects of probiotic, Lactobacillus acidophilus (La), prebiotic, inulin, or both (synbiotic, syn) on pathogen-induced inflammatory responses, NF-κB, and Smad 7 signaling. Newborn mice were inoculated bi-weekly for 4 weeks with La, inulin, or syn and challenged with Citrobacter rodentium (Cr) at 5 weeks. Mouse intestinal epithelial cells (CMT93) were exposed to Cr to determine temporal alterations in NF-Kappa B and Smad 7 levels. Mice with pretreatment of La, inulin, and syn show reduced intestinal inflammation following Cr infection compared with controls, which is associated with significantly reduced bacterial colonization in La, inulin, and syn animals. Our results further show that host defense against Cr infection correlated with enhanced colonic IL-10 and transforming growth factor-ß expression and inhibition of NF-κB in syn-treated mice, whereas mice pretreated with syn, La, or inulin had attenuation of Cr-induced Smad 7 expression. There was a temporal Smad 7 and NF-κB intracellular accumulation post-Cr infection and post-tumor necrosis factor stimulation in CMT93 cells. These results, therefore, suggest that probiotic, La, prebiotic inulin, or synbiotic may promote host-protective immunity and attenuate Cr-induced intestinal inflammation through mechanisms affecting NF-κB and Smad 7 signaling.

Infantile hypertrophic pyloric stenosis before 3 weeks of age in infants and preterm babies.

BACKGROUND: Most infantile hypertrophic pyloric stenosis (IHPS) cases are diagnosed between 3 and 12 weeks after birth. Few data exist regarding Asian infants with IHPS who are younger than 3 weeks or are preterm. The goal of this study is to identify unusual clinical manifestations, clinical course, duration of hospital stay, and complications of Asian infants with IHPS who are preterm or younger than 3 weeks of age. METHODS: From 1991 to 2004, all IHPS patients admitted to three tertiary centers in southern Taiwan were enrolled. The clinical manifestations, duration of hospital stay and complications were further compared between the IHPS patients diagnosed before and after 3 weeks; preterm and term infants. RESULTS: A total of 214 patients were enrolled into the study; the mean age of diagnosis was 40 days of age; the average duration of hospital stay was 6.27 days. Eighteen (8.41%) patients were diagnosed before 3 weeks of age. A significantly shorter timeframe of diagnosis, a higher rate of jaundice, a lower daily body weight gain and longer duration of hospital stay were noted in the IHPS group prior to 3 weeks compared with those in IHPS group after 3 weeks. Eighteen were preterm infants. A significantly older age of symptom onset, a lower body weight at admission, more cases diagnosed by barium meal study and higher postoperative complication rates were noted in the preterm group versus full-term infants with IHPS. CONCLUSIONS: The IHPS cases diagnosed before 3 weeks of age had longer duration of hospital stay. Preterm infants with IHPS had more postoperative complications.

Clinical pharmacology of antifungal agents in pediatric patients.

Invasive fungal infections have emerged as important causes of morbidity and mortality in profoundly immunocompromised children including cancer, transplant and intensive care unit patients. Present treatment strategies for these infections are limited by toxicity, drug interactions and expense. In order to overcome these limitations, new antifungal compounds are being developed, which may improve the therapeutic armamentarium for prevention and treatment of invasive mycoses in high-risk children. This article summarizes the clinical pharmacology of established and newly developed antifungal agents, including new triazoles and echinocandins in pediatric age groups.

Zygomycosis in children: a systematic review and analysis of reported cases.

BACKGROUND: Zygomycosis has emerged as an increasingly important infection with a high mortality especially in immunocompromised patients. No comprehensive analysis of pediatric zygomycosis cases has been published to date. METHODS: We used a PUBMED search for English publications of pediatric (0-18 years) zygomycosis cases and references from major books as well as single case reports or case series. Individual references were reviewed for additional cases. Data were entered into Filemaker-pro database and analyzed by logistic regression analysis. RESULTS: One hundred fifty-seven cases (64% male) were found with median age 5 years (range, 0.16-13). Underlying conditions included neutropenia (18%), prematurity (17%), diabetes mellitus (15%), ketoacidosis (10%), and no apparent underlying condition (14%). The most common patterns of zygomycosis were cutaneous (27%), gastrointestinal (21%), rhinocerebral (18%), and pulmonary (16%). Among 77 culture-confirmed cases, Rhizopus spp. (44%) and Mucor spp. (15%) were most commonly identified. Of 81 patients who were given antifungal therapy, 73% received an amphotericin B formulation only. The remaining patients received mostly amphotericin B in combination with other antifungal agents. Mortality in patients without antifungal therapy was higher than in those with therapy (88% versus 36%, P < 0.0001). Ninety-two (59%) patients underwent surgery. Cerebral, gastrointestinal, disseminated and cutaneous zygomycosis were associated with mortality rates of 100, 100, 88, and 0%, respectively. Independent risk factors for death were disseminated infection (OR: 7.18; 95% CI: 3.02-36.59) and age <1 year (OR: 3.85; 95% CI: 1.05-7.43). Antifungal therapy and particularly surgery reduced risk of death by 92% (OR: 0.07; 95% CI: 0.04-0.25) and 84% (OR: 0.16; 95% CI: 0.09-0.61), respectively. CONCLUSIONS: Zygomycosis is a life-threatening infection in children with neutropenia, diabetes mellitus, and prematurity as common predisposing factors, and there is high mortality in untreated disease, disseminated infection, and age <1 year. Amphotericin B and surgery significantly improve outcome.

Streptococcus pneumoniae bacteraemia: pharmacodynamic correlations with outcome and macrolide resistance--a controlled study.

There are few data on macrolide pharmacodynamics in pneumococcal infections. We evaluated pneumococcal area under the inhibitory concentration-time curve (AUIC) values at the point of hospital admission in 59 bacteraemic patients failing in the community and in 98 bacteraemic controls without macrolide exposure. The area under the 24-h concentration-time curve (AUC24) was calculated for each patient using age, weight and daily dose; using minimum inhibitory concentrations (MICs), the values of AUIC (i.e. AUC24/MIC) were then computed. Clinical and outcome information was also collected in hospital. Five of six patients who died of pneumococcal bacteraemia in hospital received azithromycin, with a mean AUIC of 8.1 prior to hospital admission. Resistant isolates were recovered in 35 (59%) macrolide failures and in only 28 (29%) controls (P=0.001). Azithromycin AUICs averaged 10 in failure patients and 17 in controls. For clarithromycin and erythromycin, the mean AUIC values in failures were 31 and 53, respectively, and the AUIC in controls was >100. Low AUIC values against Streptococcus pneumoniae precede macrolide failures in the community. Patient factors do not predict these outcomes and thus the most likely explanation for macrolide failure in the community is inadequate macrolide activity in patients who receive these antibiotics for treatment of organisms that are not sufficiently susceptible.

Concomitant Candida epiglottitis and disseminated Varicella zoster virus infection associated with acute lymphoblastic leukemia.

Acute epiglottitis by nonbacterial pathogens is an uncommon but life-threatening clinical entity. Herein, we report the concomitant occurrence of Candida epiglottitis and mucosal and visceral Varicella zoster virus infection in a child with acute lymphoblastic leukemia. Both infections were atypical in their presentation, occurred in a severely immunocompromised host, and required invasive procedures for diagnosis.

Severe pneumococcal pneumonia: new strategies for management.

PURPOSE OF REVIEW: Streptococcus pneumoniae is the leading cause of community-acquired pneumonia worldwide and is the most likely causative pathogen in patients with community-acquired pneumonia admitted to the intensive care unit. Bacteremic pneumococcal pneumonia is an advanced stage of severe pneumococcal pneumonia. Improvement in the management of bacteremic pneumococcal pneumonia has the potential for improving the survival for severe pneumococcal pneumonia. RECENT FINDINGS: Non-culture methods, especially the Binax urinary antigen test, can increase the diagnostic yield for pneumococcal pneumonia, allowing targeted antimicrobial therapy (specifically penicillin). In-vitro resistance to penicillin has increased over the past decade; however, it has not led to clinical failure when used for pneumococcal pneumonia. SUMMARY: Hospitalized patients with community-acquired pneumonia should have blood cultures obtained to confirm the possibility of bacteremic pneumococcal pneumonia. Based on pharmacodynamic properties, parenteral penicillin remains the drug of choice to treat pneumococcal pneumonia regardless of in-vitro resistance. Combination antimicrobial therapy will likely improve survival of patients with bacteremic pneumococcal pneumonia among the subset of critically ill patients.

Serotype and antimicrobial resistance patterns of Streptococcus pneumoniae isolated from Taiwanese children: comparison of nasopharyngeal and clinical isolates.

This report describes the serotypes and antimicrobial resistance patterns of 860 strains of Streptococcus pneumoniae isolated from nasopharyngeal (NP) carriers and clinical specimens collected from Taiwanese children during the years 1997 to 2003. The 6 most common serotypes/groups were 23F, 19F, 6B, 14, 6A, and 3. These accounted for 652/716 (91.1%) of the NP and 131/144 (91.0%) of the clinical isolates. Serotype 23F was the most common isolate in the NP carriers (25.7%, 184/716). Serogroup14 was most common in the clinical isolates (29.2%, 42/144) and the most frequent invasive isolate (43.4%, 33/76). It was more frequently associated with invasive infection than all other serotypes/groups (odds ratio = 7.2; 95% confidence interval, 4.16-12.46; P < .0001). Resistance to macrolides was high in all serotypes/groups, which ranged from 70% to 97%. Resistance to penicillin varied among the 6 leading serotypes/groups, ranging from 3% in serogroup 3 to 99% in serotype 19F. Serotype 23F was most likely to be multidrug resistant to penicillin, macrolides, and chloramphenicol compared with all others (107/150 [71%] versus 105/461 [23%], P < .0001). The potential coverage by the pentavalent and heptavalent vaccines was 83% for all isolates, but was significantly lower for NP than clinical isolates (81% versus 92%, P< .01). These findings provide baseline data to compare trends in the distribution of pneumococcal serotypes and antibiotic resistance patterns with the introduction of childhood pneumococcal vaccination in Taiwan and other countries.

Problem pathogens: paediatric legionellosis--implications for improved diagnosis.

Legionnaires' disease is an established and frequent cause of pneumonia in adults but is thought to be a rare cause in children. We reviewed the medical literature for cases of Legionnaires' disease in children and analysed the epidemiology, clinical characteristics, and treatment. 76 cases of legionella infection in children were identified. In 56%, diagnosis was made with culture methodology. 46% were community-acquired infections. 51.5% were under 2 years of age. 78% of the patients had an underlying condition such as malignancy. Fever, cough, and tachypnoea were the most common symptoms. The overall mortality rate was 33% and was higher in immunosuppressed children and in children younger than the age of 1 year. Patients who were treated empirically with anti-legionella therapy had a notably lower mortality rate compared with patients on inappropriate therapy (23%vs 70%). In 88% of hospital-acquired cases, an environmental link to potable water colonised with legionella was identified. We found no clinical features unique to Legionnaires' disease in children that would allow differentiation from pneumonia due to other respiratory pathogens. Awareness of legionella as a potential cause of paediatric pneumonia is particularly important because infection can be severe and life threatening and antimicrobial therapy often used for empirical therapy in children is not effective against legionella. In any case of pneumonia unresponsive to antibiotics, Legionnaires' disease should be considered and specific diagnostic tests to verify this diagnosis should be done. As legionella diagnostic tests become more widely applied, we predict that legionellosis may appear as an emerging infectious disease in children.

High carriage rate of high-level penicillin-resistant Streptococcus pneumoniae in a Taiwan kindergarten associated with a case of pneumococcal meningitis.

BACKGROUND: The Taiwan19F-14 Streptococcus pneumoniae clone and its variants are being found with increasing frequency in the Asia-Pacific region. A 5-year old child with S. pneumoniae meningitis caused by a high-level penicillin resistant strain (MIC = 4 microg/ml) was admitted to a hospital in southern Taiwan. We carried out a study to determine the potential source of this strain. METHODS: Nasopharyngeal cultures were obtained from all children attending the same kindergarten as the index case. To determine their relatedness all isolates were compared by serotype, antimicrobial susceptibility profile and pulsed field gel electrophoresis (PFGE). RESULTS: A high proportion of the children including the index case (32/78, 41.0%) carried S. pneumoniae in their nasopharynx (NP). The most common serotype was 19F (13/32, 40.6%). The PFGE types of the 19F serotype isolates obtained from the patient's blood, CSF and NP were identical and were related to 11 other serotype 19F NP isolates including 10 that were indistinguishable from the Taiwan19F-14 clone. All 14 isolates had similar high-level penicillin and multi-drug resistance. The serotypes of the other 19 NP isolates included 6A (2), 6B (10), 23F (5), 9V (1) and 3 (1). The overall rate of penicillin resistance in these S. pneumoniae from these children was 87.5% (28/32), with an MIC50 of 2 and MIC90 of 4 ug/ml. In addition, multi-drug resistant-isolates (isolates resistant to 3 different classes of antimicrobials) accounted for 87.5% (28/32) of all isolates. CONCLUSION: The high carriage rate of high-level penicillin- and multi-drug- resistant S. pneumoniae in a kindergarten associated with a case of pneumococcal meningitis emphasizes the need for restraint in antibiotic use and consideration of childhood immunization with conjugate pneumococcal vaccine to prevent the further spread of resistant S. pneumoniae in Taiwan.

Epidemiology and outcome of zygomycosis: a review of 929 reported cases.

BACKGROUND: Zygomycosis is an increasingly emerging life-threatening infection. There is no single comprehensive literature review that describes the epidemiology and outcome of this disease. METHODS: We reviewed reports of zygomycosis in the English-language literature since 1885 and analyzed 929 eligible cases. We included in the database only those cases for which the underlying condition, the pattern of infection, the surgical and antifungal treatments, and survival were described. RESULTS: The mean age of patients was 38.8 years; 65% were male. The prevalence and overall mortality were 36% and 44%, respectively, for diabetes; 19% and 35%, respectively, for no underlying condition; and 17% and 66%, respectively, for malignancy. The most common types of infection were sinus (39%), pulmonary (24%), and cutaneous (19%). Dissemination developed in 23% of cases. Mortality varied with the site of infection: 96% of patients with disseminated disease died, 85% with gastrointestinal infection died, and 76% with pulmonary infection died. The majority of patients with malignancy (92 [60%] of 154) had pulmonary disease, whereas the majority of patients with diabetes (222 [66%] of 337) had sinus disease. Rhinocerebral disease was seen more frequently in patients with diabetes (145 [33%] of 337), compared with patients with malignancy (6 [4%] of 154). Hematogenous dissemination to skin was rare; however, 78 (44%) of 176 cutaneous infections were complicated by deep extension or dissemination. Survival was 3% (8 of 241 patients) for cases that were not treated, 61% (324 of 532) for cases treated with amphotericin B deoxycholate, 57% (51 of 90) for cases treated with surgery alone, and 70% (328 of 470) for cases treated with antifungal therapy and surgery. By multivariate analysis, infection due to Cunninghamella species and disseminated disease were independently associated with increased rates of death (odds ratios, 2.78 and 11.2, respectively). CONCLUSIONS: Outcome from zygomycosis varies as a function of the underlying condition, site of infection, and use of antifungal therapy.

Outbreak of dysentery associated with ceftriaxone-resistant Shigella sonnei: First report of plasmid-mediated CMY-2-type AmpC beta-lactamase resistance in S. sonnei.

We document the first report of plasmid-encoded CMY-2-type AmpC beta-lactamase identified among Shigella sonnei isolates resistant to ceftriaxone and obtained after an outbreak of bacillary dysentery in Taiwan. One hundred eighty-two children in two elementary schools in Yu-Li, Taiwan, where an outbreak occurred after a typhoon hit this area in 2001, were enrolled in this study. Clinical and epidemiologic data on the infected children were collected. Pulsed-field gel electrophoresis (PFGE) was performed on the isolates to determine the genetic relatedness of outbreak strains. Plasmid analysis and PCR were performed to identify beta-lactamase genes responsible for ceftriaxone resistance. Forty-seven children from the two elementary schools were culture positive for S. sonnei in this outbreak. Twenty-three children were asymptomatic. Of the total isolates 55.3% were resistant to ampicillin. One hundred percent of the isolates obtained from children in school A were initially susceptible to both ampicillin and ceftriaxone. Of isolates obtained from school B 96.2% were nonsusceptible to ceftriaxone. However, two isolates from school A developed resistance to ampicillin during the course of treatment. All 18 available isolates showed closely related PFGE patterns (4, 4a, 4b, and 4c). CMY-2-type AmpC beta-lactamase was responsible for ceftriaxone resistance in ceftriaxone-nonsusceptible isolates; Southern blot hybridization confirmed that such a resistance gene was located on the plasmid. This is the first report of plasmid-mediated CMY-2-type AmpC beta-lactamase in S. sonnei. Ampicillin-resistant isolates can develop during the course of antibiotic treatment.

Newer systemic antifungal agents : pharmacokinetics, safety and efficacy.

The past few years have seen the advent of several new antifungal agents, including those of a new class and a new generation of an existing class. Caspofungin, the first available echinocandin, has greatly expanded the antifungal armamentarium by providing a cell wall-active agent with candidacidal activity as well as demonstrated clinical efficacy in the therapy of aspergillosis refractory to available therapy. In addition, in clinical trials, caspofungin had comparable efficacy to amphotericin B for candidaemia and invasive Candida infections. Caspofungin and two more recently introduced echinocandins, micafungin and anidulafungin, are available as intravenous formulations only and characterised by potent anti-candidal activity, as well as few adverse events and drug interactions. Voriconazole, the first available second-generation triazole, available in both intravenous and oral formulations, has added a new and improved therapeutic option for primary therapy of invasive aspergillosis and salvage therapy for yeasts and other moulds. In a randomised trial, voriconazole demonstrated superior efficacy and a survival benefit compared with amphotericin B followed by other licensed antifungal therapy. This and data from a noncomparative study led to voriconazole becoming a new standard of therapy for invasive aspergillosis. Voriconazole has several important safety issues, including visual adverse events, hepatic enzyme elevation and skin reactions, as well as a number of drug interactions. Posaconazole, only available orally and requiring dose administration four times daily, shows encouraging efficacy in difficult to treat infections due to zygomycetes. Ravuconazole, available in both intravenous and oral formulations, has broad-spectrum in vitro potency and in vivo efficacy against a wide range of fungal pathogens. Clinical studies are underway. Despite the advances offered with each of these drugs, the morbidity and mortality associated with invasive fungal infections remains unacceptable, especially for the most at-risk patients. For individuals with severe immunosuppression as a result of chemotherapy, graft-versus-host disease and its therapy, or transplantation, new drugs and strategies are greatly needed.

Necrotizing pneumonitis caused by Mycoplasma pneumoniae in pediatric patients: report of five cases and review of literature.

Mycoplasma pneumoniae infection is usually self-limited without severe sequelae. We report 5 pediatric patients with necrotizing pneumonitis caused by Mycoplasma pneumoniae and reviewed the reported cases in the English language. Protracted course of fever and respiratory distress were noted in all 5 patients. Macrolides and adequate chest tube drainage for pleural effusion were the mainstay of treatment.

Combination antibiotic therapy lowers mortality among severely ill patients with pneumococcal bacteremia.

Retrospective studies have suggested that combination antibiotic therapy for severe bacteremic pneumococcal pneumonia may reduce mortality. We assessed this issue in a prospective, multicenter, international observational study of 844 adult patients with bacteremia due to Streptococcus pneumoniae. The effect of combination antibiotic therapy versus monotherapy on mortality was examined by univariate analyses and by logistic regression models. The 14-day mortality was not significantly different for the two groups. However, among critically ill patients, combination antibiotic therapy was associated with lower 14-day mortality (23.4 versus 55.3%, p = 0.0015). This improvement in survival was independent of country of origin, intensive care unit support, class of antibiotics, or in vitro activity of the antibiotics prescribed. Combination antibiotic therapy improved survival among critically ill patients with bacteremic pneumococcal illness.

Nontyphoid salmonellosis in taiwan children: clinical manifestations, outcome and antibiotic resistance.

OBJECTIVES: The purposes of this study were to investigate the epidemiologic, clinical, and microbiologic features of patients with nontyphoid salmonellosis and to elucidate the impact of resistance on the outcome of nontyphoid salmonellosis in Taiwan. The authors also sought to develop a severity score to derive an objective guideline for antibiotic use in nontyphoid salmonellosis in the era of increasing antibiotic resistance. METHODS: The authors prospectively monitored 311 children with nontyphoid salmonellosis in Kaohsiung, Taiwan. The demographic, clinical, and microbiologic features, underlying diseases, treatment regimen, complications, and outcome were analyzed. In vitro susceptibility testing of the isolates was performed. RESULTS: The median age of affected patients was 15 months. Salmonella enteritidis B caused 68.5% of episodes, followed by S. enteritidis C1 (11.9%), D (7.7%), C2 (7.1%), E (2.6%), S. choleraesuis (1.6%), and S. paratyphi (0.6%). Sixty percent of isolates were resistant to ampicillin. Patients with bacteremia could not be differentiated from patients without bacteremia on clinical grounds. Patients receiving antibiotics that were inactive in vitro (discordant therapy) had more days of fever and longer hospital stay compared with patients receiving antibiotics that were active in vitro (concordant therapy). Patients receiving no antibiotic treatment had the fewest days of fever and shortest hospital stays, especially among patients with mild illness (severity score, 0-1). CONCLUSION: Blood culture should be obtained in patients with nontyphoid salmonellosis to detect bacteremia. In treating antibiotic-resistant nontyphoid salmonellosis, antibiotics are still not mandatory for patients who present with primarily gastrointestinal symptoms and limited signs of systemic inflammation reflected by a low severity score (low C-reactive protein, fewer band cells in peripheral blood, and fewer days of fever before admission). Susceptibility data should be promptly obtained because use of discordant antibiotics appears to prolong illness.

An international prospective study of pneumococcal bacteremia: correlation with in vitro resistance, antibiotics administered, and clinical outcome.

We performed a prospective, international, observational study of 844 hospitalized patients with blood cultures positive for Streptococcus pneumoniae. Fifteen percent of isolates had in vitro intermediate susceptibility to penicillin (minimum inhibitory concentration [MIC], 0.12-1 microg/mL), and 9.6% of isolates were resistant (MIC, >or=2 microg/mL). Age, severity of illness, and underlying disease with immunosuppression were significantly associated with mortality; penicillin resistance was not a risk factor for mortality. The impact of concordant antibiotic therapy (i.e., receipt of a single antibiotic with in vitro activity against S. pneumoniae) versus discordant therapy (inactive in vitro) on mortality was assessed at 14 days. Discordant therapy with penicillins, cefotaxime, and ceftriaxone (but not cefuroxime) did not result in a higher mortality rate. Similarly, time required for defervescence and frequency of suppurative complications were not associated with concordance of beta-lactam antibiotic therapy. beta-Lactam antibiotics should still be useful for treatment of pneumococcal infections that do not involve cerebrospinal fluid, regardless of in vitro susceptibility, as determined by current NCCLS breakpoints.