Spread of the serotype 23F multidrug-resistant Streptococcus pneumoniae clone to South Korea

We report the case of 61-year-old woman with cryptogenic liver abscesses who had been profoundly ill with severe upper abdominal pain, impaired consciousness, prostration, continuous high fever secondary to sepsis, and thrombocytopenia (platelets, 1-5 x 10(4)/mm3) since admission. Ultrasonograms and computed tomograms revealed two separate multiloculated lesions in the right lobe of the liver, consistent with the liver abscesses. Immediately after diagnosis, percutaneous abscess drainage was performed under ultrasonographic guidance; however, only a small amount of pus was drained, prompting continuous irrigation of the abscess cavity. Four days later, transcatheter hepatic arterial infusion of antibiotics was attempted. However, the abscesses had enlarged and her general condition had worsened. On hospital day 8, she underwent right hepatectomy because the multiloculated lesions were refractory to drainage. The operation was successful in terms of hepatectomy, although she continued to suffer from sepsis, secondary right subphrenic abscess formation, and prolonged thrombocytopenia with associated coagulation disorders for two months. Examination of multiple cross sections of the resected specimen disclosed that the lesions consisted of aggregations of multiple small locules. There was no communication between the locules and there were true septations, rather than multiloculated lesions with pseudoseptations. The patient has been well for 2 years without recurrent abscess of the liver or any infectious disease.     

Capsular transformation of a multidrug-resistant Streptococcus pneumoniae in vivo

OBJECTIVE: To evaluate the effects of a mandibular advancement device on apneas and sleep in mild, moderate, and severe obstructive sleep apnea. DESIGN: Prospective study. SUBJECTS: Forty-four of 47 patients included. INTERVENTION: Individually adjusted mandibular advancement devices. MEASUREMENTS: Polysomnographic sleep recordings for 1 night without the device and 1 night with it, with a median of 1 day and no changes in weight, medication, or sleep position between the recordings. RESULTS: The device reduced the median obstructive apnea-hypopnea index from 11 (range, 7 to 19) to 5 (range, 0 to 17) (p<0.001) in 21 patients with mild sleep apnea, from 27 (range, 20 to 38) to 7 (range, 1 to 19) (p<0.001) in 15 patients with moderate sleep apnea, and from 53 (range, 44 to 66) to 14 (range, 2 to 32) (p<0.05) in 8 patients with severe sleep apnea. The arousal index decreased and the sleep stage patterns improved in all severity groups. Twenty-eight of 44 patients were successfully treated with an obstructive apnea-hypopnea index of below 10 and a subjective reduction in snoring. Nine of 16 patients with treatment failure still reported a reduction in snoring. The success rate correlated inversely to the disease severity (r=-0.41; p<0.01). CONCLUSIONS: A mandibular advancement device reduces apneas and improves sleep quality in patients with obstructive sleep apnea, especially in those with mild and moderate disease. A follow-up sleep recording during treatment is necessary because of the risk of silent obstructive apneas without subjective snoring with the device.     

The impact of HIV on Streptococcus pneumoniae bacteraemia in a South African population

OBJECTIVES: To determine the impact of HIV infection on Streptococcus pneumoniae bacteraemia in adults and children by analysing the prevalence and clinical features of such diseases and determining the prevalent serotypes/serogroups and susceptibility patterns of isolates. DESIGN: Patients were identified prospectively from January to October 1996. SETTING: Chris Hani Baragwanath Hospital, Soweto, a tertiary referral hospital treating adults and children, in an urban district near Johannesburg, South Africa. PATIENTS AND METHODS: All patients with S. pneumoniae isolated from blood culture by the Microbiology Department, Chris Hani Baragwanath Hospital were studied. Clinical and microbiological features were recorded. RESULTS: A total of 178 patients with S. pneumoniae were investigated as part of the study; 49 were aged < 13 years. HIV seroinfection was present in 25 (51%) children and 58 (45%) adults. The incidence of S. pneumoniae bacteraemia was 36.9-fold increased in HIV-seropositive children and 8.2-fold increased in HIV-seropositive adults compared with HIV-seronegative individuals. Both adult and paediatric HIV-seropositive patients with S. pneumoniae bacteraemia were significantly younger than HIV-seronegative patients. Pneumonia was a significantly more common presentation in HIV-seropositive children, otherwise the spectrum of disease and outcome were similar in HIV-seronegative and positive groups. Serotype 1 S. pneumoniae isolates were significantly less common in HIV-infected individuals (both adults and children). Resistance to penicillin was increased in S. pneumoniae isolates from HIV-infected patients (significant in adults). Patients with penicillin-resistant isolates did not have a poorer outcome. The potential coverage of serotypes/serogroups included in the proposed nine-valent conjugate pneumococcal vaccine was 88% in HIV-seronegative children and 83% in HIV-seropositive children. The potential coverage of the currently available 23-valent pneumococcal vaccine for adults was 98.2 and 100)% for HIV-infected and HIV-uninfected adults, respectively. CONCLUSION: The burden of bacteraemia due to S. pneumoniae in HIV-seropositive individuals admitted to our hospital is considerable. Differences in the S. pneumoniae serotypes/serogroups in HIV-infected patients have been demonstrated with resultant differences in antibiotic susceptibility patterns. Excellent potential for vaccine coverage was demonstrated for both HIV-seronegative and HIV-seropositive individuals. Further studies are necessary to test the clinical efficacy of pneumococcal vaccination of HIV-seropositive adults and children as a potential preventative measure against this prevalent disease.     

Drug-resistant Streptococcus pneumoniae

Streptococcus pneumoniae remains a major cause of infection in both children and adults, annually resulting in significant morbidity and mortality. The past two decades have seen an alarming worldwide increase in the incidence of drug-resistant S. pneumoniae (DRSP). DRSP is now common throughout the United States, and physicians are questioning how best to approach this epidemic. With the introduction of a number of newer antimicrobial agents, the potential for improved preventive measures, and a better understanding of DRSP, the approach to the management of DRSP infections may change greatly in the next few years. In this article we will review the development of DRSP, identify populations at increased risk of exposure to DRSP, address what approaches might be used to limit its spread, and suggest initial empirical therapy when treating patients with pneumonia due to DRSP.     

Multivariate analysis of risk factors for infection due to penicillin-resistant and multidrug-resistant Streptococcus pneumoniae: a multicenter study

Pneumococcal disease was studied prospectively to determine the risk factors associated with resistance to penicillin and other antibiotics. One hundred twelve clinically significant pneumococcal isolates were recovered from 95 patients. Approximately one-half (49.47%) of the cases were due to penicillin-resistant strains. Multivariate analysis showed that previous use of beta-lactam antibiotics (odds ratio [OR], 2.81; 95% confidence interval [CI], 0.95-8.27), alcoholism (OR, 5.22; 95% CI, 1.43-19.01), and noninvasive disease (OR, 4.53; 95% CI, 1.54-13.34) were associated with penicillin resistance, whereas intravenous drug use (OR, 0.14; 95% CI, 0.03-0.74) was not. Statistical analyses of the variables associated with resistance to multiple antibiotics detected age of younger than 5 years (OR, 16.79; 95% CI, 1.60-176.34) or of 65 years or older (OR, 4.33; 95% CI, 1.42-13.21) and previous use of beta-lactam antibiotics by patients with noninvasive disease (OR, 7.92; 95% CI, 1.84-34.06) as parameters associated with increased risk. We conclude that multivariate analysis provides clues for empirical therapy for pneumococcal infection.     

Multiple antibiotic resistance in Streptococcus pneumoniae

A 40-year-old Libyan male was admitted to the intensive therapy unit of Zliten Central Hospital, Libya after a road traffic accident in which he had been the driver. On physical examination he was irritable, dyspnoeic, cyanotic, had contusions and abrasions on his chest and abdomen (mainly on the left side), a lacerated wound on the forehead, a large haematoma over the left thigh and tenderness over the left side of the chest and abdomen.     

Primary targets of fluoroquinolones in Streptococcus pneumoniae

Mutants of wild-type Streptococcus pneumoniae IID553 with mutations in parC were obtained by selection with trovafloxacin, levofloxacin, norfloxacin, and ciprofloxacin. All of the parC mutants were cross-resistant to the selecting agents but were not resistant to gatifloxacin and sparfloxacin. On the other hand, gyrA mutants were isolated by selection with gatifloxacin and sparfloxacin. The gyrA mutants were cross-resistant to gatifloxacin and sparfloxacin but were not resistant to the other fluoroquinolones tested. These results suggest that in wild-type S. pneumoniae the primary target of trovafloxacin, levofloxacin, norfloxacin, and ciprofloxacin is topoisomerase IV, whereas the primary target of gatifloxacin and sparfloxacin is DNA gyrase.     

Strategies in the treatment of penicillin-resistant Streptococcus pneumoniae

The epidemiology, resistance mechanisms, susceptibility testing, treatment, prevention, and clinical importance of penicillin-resistant Streptococcus pneumoniae (PRSP) infection are discussed. PRSP is an established presence in the United States, with some geographic areas reporting decreased susceptibility in up to half of isolates. The mechanism of resistance to beta-lactam antibiotics in S. pneumoniae is genetic changes resulting in decreased binding of drug to the bacterial cell wall. Emerging PRSP strains have necessitated testing as a tool in selecting drugs for treating life-threatening infections. Opinions differ on how to treat these infections empirically. Non-life-threatening infections, such as otitis media, are still often treated successfully with amoxicillin, amoxicillin-clavulanate potassium, or a third-generation cephalosporin. Currently recommended initial treatment of pneumococcal pneumonia in otherwise healthy patients requiring hospitalization consists of cefuroxime, ceftriaxone, or cefotaxime; some authors continue to emphasize injectable penicillin. Once the mainstay of empirical treatment of pneumococcal meningitis, penicillin has largely been abandoned in favor of cefotaxime or ceftriaxone. Vaccination remains an underutilized strategy in atrisk populations. The clinical importance of penicillin resistance among pneumococci is still uncertain. Changing patterns in the susceptibility of S. pneumoniae to penicillin make selection of appropriate therapy increasingly difficult. Key considerations are the site of infection and the level of resistance.     

Primary peritonitis caused by Streptococcus pneumoniae

OBJECTIVES: To examine the dilemmas for children, family, and mental health professionals posed by the presence of a delusional parent in a family, including someone with induced psychotic disorder (IPD); to identify frequently unrecognized problems; and to propose practical suggestions for professionals. METHOD: The pertinent literature on the effects of delusional parents on children, families, and professionals is reviewed. By way of 3 case vignettes, the dilemmas are identified and discussed. RESULTS: Delusional disorders are underdiagnosed, resulting in poor anticipation of their implications. Unanticipated family factors, such as "pursuit of isolation" and the related heightened risk of violence, contribute to the failure of professional interventions, which has been described as "therapeutic systems paralysis." CONCLUSIONS: These cases are complex, often requiring multisystemic involvement to reduce the risks of flight. violence, psychosis, posttraumatic stress disorder, and other psychiatric sequelae to children and other family members. The critical features of the innovative collaboration ("therapeutic consensus") required between professionals for successful therapeutic interventions with these families are described.     

Streptococcus pneumoniae and beta-lactam antibiotic agents

Pneumococcus has been known for over 100 years. Despite an intensive research, the problem of pneumococcal diseases has not yet been solved. During the last few decades, the incidence of pneumococcal pneumonia has declined, but the S. pneumoniae is today the main, or one of the most frequent, causative agents of meningitis, sinusitis, otitis media and conjunctivitis. Besides, cases of pneumococcal appendicitis, tubo-ovarian abscess, haemolytico-uremic syndrome, cellulitis and urinary infections have been described. Therefore, it is very important from medical point of view to follow-up its sensitivity to antibacterial drugs. Unfortunately, during the latest decades, an increase in percentage of resistant clinical isolates has been registered. It is obvious that the investigation of the sensitivity of pneumococci, that is, of their resistance to beta-lactam antibiotics is essential. The examination of the interaction between pneumococci and penicillin has resulted in significant discoveries concerning the mechanism of the effect of penicillin as well as the impact of penicillin-binding proteins, lipoteichoic acid and choline-residues in the cell wall. A particular contribution as regards the effect of penicillin has been achieved by linking murein hydrolases (autolythic enzymes) with the expression of bactericidal effect of penicillin. Besides, the model of pneumococcal resistance to penicillin together with the model of meticillin resistance of staphylococci enabled the perception of the new mechanism of bacteria resistance to beta-lactam antibiotics. Given the pathogenic potential of pneumococci and the increase of clinical isolates resistant to antibiotics, it can be concluded that immunoprophylaxis is of great importance. Although several polyvalent vaccines are being used, there are still unsolved problems whose solution will improve the safety of their application, contribute to a better efficiency and enable a widespread application of antipneumococcal vaccines.     

Septic arthritis caused by Streptococcus pneumoniae

BACKGROUND: Streptococcus pneumoniae is an uncommon agent of infective arthritis. In this report three cases of pneumococcal arthritis are described. METHODS: Retrospective review of synovial fluids processed in our laboratory yielding bacteria. The study period was from January 1991 to December 1995. The clinical records of patients with the clinical and microbiological diagnosis of septic arthritis were reviewed. RESULTS: Twenty-eight out of a total of 43 clinical records had the clinical and microbiological diagnosis of septic arthritis and three (11%) were caused by Streptococcus pneumoniae. The infective source in two of these three cases was probably the respiratory tract, and the most common location was the knee. CONCLUSIONS: In our cases immunosuppression seemed to be the major risk factor involved in the development of pneumococcal arthritis.     

Primary peritonitis due to Streptococcus pneumoniae in childhood

Three patients, two boys of 5 months and 6 years and one girl aged 4 years, presented with acute abdominal pain, vomiting and fever, suggesting peritonitis. Imaging examinations (abdominal survey roentgenogram and (or) echography), exploratory laparotomy (in two patients) and blood cultures with growth of Streptococcus pneumoniae led to the diagnosis of primary peritonitis. Intravenous antibiotics led to recovery, in one patient complicated by paralytic ileus, which was treated surgically. Primary peritonitis is a rare condition which should be considered in the differential diagnosis of children with an acute abdominal syndrome. Conditions requiring surgery should be excluded by imaging examinations or laparotomy. When the diagnosis is confirmed by paracentesis or laparotomy, antibiotic treatment has to be started.     

Resistance to antibiotics of Streptococcus pneumoniae strains

Streptococcus pneumoniae strains are exhibiting increasing rates of antibiotics resistance. A rapid increase of resistance was seen not only to penicillin but also other antimicrobial agents and therefore this paper describes the study of resistance and multiresistance of pneumococci to 7 antibiotics: penicillin (P), erythromycin (E), clindamycin (CC), tetracycline (T), co-trimoxazole (SXT), cefotaxime (CTX) and vancomycin (Va), using the disk-diffusion technique according to NCCLS procedure. We tested a total of 218 S. pneumoniae strains isolated from various materials: from sputum (54), noses (117), throats (28) and different swabs specimens (19). The overall percentage of resistant isolates to penicillin was 3.7%, to erythromycin--4.1%, to clindamycin--10.6%, to tetracycline--17.4%, to co-trimoxazole--15.6%, to cefotaxime--2.3%. In the sputum was most the monoresistant strains (66.7%). The multiresistance was highest in the penicillin resistant pneumococci. With the exception of vancomycin, the number of resistant strains to non-beta-lactam antibiotics (erythromycin, clindamycin, tetracycline, co-trimoxazole) was higher in penicillin-resistant strains compared with penicillin susceptible isolates. All isolates were susceptible to vancomycin.     

Management of infections due to antibiotic-resistant Streptococcus pneumoniae

Antibiotic-resistant strains of Streptococcus pneumoniae are becoming more prevalent throughout the world; this has resulted in modifications of treatment approaches. Management of bacterial meningitis has the greatest consensus. Strategies for treating other systemic infections such as pneumonia, bacteremia, and musculoskeletal infections are evolving, in part related to the availability of new antibiotics which are active in vitro against isolates resistant to penicillin and the extended-spectrum cephalosporins. However, there are currently very limited data related to the clinical efficacy of these new agents. The studies upon which current recommendations are based are reviewed. Otitis media represents the single most common infection due to S. pneumoniae. Recommendations for treatment of acute otitis media due to drug-resistant strains and the rationale for these recommendations are discussed.     

Large-scale identification of virulence genes from Streptococcus pneumoniae

Streptococcus pneumoniae is the major cause of bacterial pneumonia, and it is also responsible for otitis media and meningitis in children. Apart from the capsule, the virulence factors of this pathogen are not completely understood. Recent technical advances in the field of bacterial pathogenesis (in vivo expression technology and signature-tagged mutagenesis [STM]) have allowed a large-scale identification of virulence genes. We have adapted to S. pneumoniae the STM technique, originally used for the discovery of Salmonella genes involved in pathogenicity. A library of pneumococcal chromosomal fragments (400 to 600 bp) was constructed in a suicide plasmid vector carrying unique DNA sequence tags and a chloramphenicol resistance marker. The recent clinical isolate G54 was transformed with this library. Chloramphenicol-resistant mutants were obtained by homologous recombination, resulting in genes inactivated by insertion of the suicide vector carrying a unique tag. In a mouse pneumonia model, 1.250 candidate clones were screened; 200 of these were not recovered from the lungs were therefore considered virulence-attenuated mutants. The regions flanking the chloramphenicol gene of the attenuated mutants were amplified by inverse PCR and sequenced. The sequence analysis showed that the 200 mutants had insertions in 126 different genes that could be grouped in six classes: (i) known pneumococcal virulence genes; (ii) genes involved in metabolic pathways; (iii) genes encoding proteases; (iv) genes coding for ATP binding cassette transporters; (v) genes encoding proteins involved in DNA recombination/repair; and (vi) DNA sequences that showed similarity to hypothetical genes with unknown function. To evaluate the virulence attenuation for each mutant, all 126 clones were individually analyzed in a mouse septicemia model. Not all mutants selected in the pneumonia model were confirmed in septicemia, thus indicating the existence of virulence factors specific for pneumonia.     

Mechanism of sulfonamide resistance in clinical isolates of Streptococcus pneumoniae

The genetic basis of sulfonamide resistance in six clinical isolates of Streptococcus pneumoniae was demonstrated to be 3- or 6-bp duplications within sulA, the chromosomal gene encoding dihydropteroate synthase. The duplications all result in repetition of one or two amino acids in the region from Arg58 to Tyr63, close to but distinct from the sul-d mutation, a duplication previously reported in a resistant laboratory strain (P. Lopez, M. Espinosa, B. Greenberg, and S. A. Lacks, J. Bacteriol. 169:4320-4326, 1987). Six sulfonamide-susceptible clinical isolates lacked such duplications. The role of the duplications in conferring sulfonamide resistance was confirmed by transforming 319- or 322-bp PCR fragments into the chromosome of a susceptible recipient. Two members of a clone of serotype 9V, one susceptible and one resistant to sulfonamide, which are highly related by other criteria, were shown to have sulA sequences that differ in 7.2% of nucleotides in addition to the duplication responsible for resistance. It is postulated that horizontal gene exchange has been involved in the acquisition (or loss) of resistance within this clone. However, five of the six resistant isolates have distinct duplications and other sequence polymorphisms, suggesting that resistance has arisen independently on many occasions.     

Antibiotic resistance of clinical isolates of Streptococcus pneumoniae in Greece

The antibiotic susceptibilities of 1,002 Streptococcus pneumoniae clinical isolates from patients with community-acquired pneumonia were determined over an 18-month period. Resistance rates were 14% for penicillin, 20% for erythromycin, 26% for tetracycline, and 1% for chloramphenicol. Resistance to non-beta-lactam antibiotics was associated with penicillin resistance at statistically levels.