Group A beta-hemolytic streptococcal infections

GABHS is the most common bacterial cause of tonsillopharyngitis, but this organism also produces acute otitis media; pneumonia; skin and soft-tissue infections; cardiovascular, musculoskeletal, and lymphatic infections; bacteremia; and meningitis. Most children and adolescents who develop a sore throat do not have GABHS as the cause; their infection is viral in etiology. Other bacterial pathogens produce sore throat infrequently (e.g., Chlamydia pneumoniae and Mycoplasma pneumoniae), and when they do, other concomitant clinical illness is present. Classic streptococcal tonsillopharyngitis has an acute onset; produces concurrent headache, stomach ache, and dysphagia; and upon examination is characterized by intense tonsillopharyngeal erythema, yellow exudate, and tender/enlarged anterior cervical glands. Unfortunately only about 20% to 30% of patients present with classic disease. Physicians overdiagnose streptococcal tonsillopharyngitis by a wide margin, which almost always leads to unnecessary treatment with antibiotics. Accordingly, use of throat cultures and/or rapid GABHS detection tests in the office is strongly advocated. Their use has been shown to be cost-effective and to reduce antibiotic overprescribing substantially. Penicillin currently is recommended by the American Academy of Pediatrics and American Heart Association as first-line therapy for GABHS infections; erythromycin is recommended for those allergic to penicillin. Virtually all patients improve clinically with penicillin and other antibiotics. However, penicillin treatment failures do occur, especially in tonsillopharyngitis in which 5% to 35% of patients do not experience bacteriologic eradication. Penicillin treatment failures are more common among patients who have been treated recently with the drug. Cephalosporins or azithromycin are preferred following penicillin treatment failures in selected patients as first-line therapy, based on a history of penicillin failures or lack of compliance and for impetigo. GABHS remain exquisitely sensitive to penicillin in vitro. There are several explanations for penicillin treatment failures, but the possibility of copathogen co-colonization in vivo has received the most attention. Treatment duration with penicillin should be 10 days to optimize cure in GABHS infections. A 5-day regimen is possible and approved by the United States Food and Drug Administration for cefpodoxime (a cephalosporin) and azithromycin (a macrolide). Prevention of rheumatic fever is the primary objective for antibiotic therapy of GABHS infections, but a reduction in contagion and faster clinical improvement also can be achieved. Development of streptococcal toxic shock syndrome and necrotizing fasciitis ("flesh-eating bacteria") are rising concerns. The portal of entry for these invasive GABHS strains is far more often skin and soft tissue than the tonsillopharynx.     

Significance of normal oropharyngeal flora in the development of streptococcal pharyngitis and outcome of penicillin therapy

Pharyngitis is one of the most frequent diseases in children. The most important of the bacterial infections is due to Streptococcus pyogenes. For many years, penicillin is considered to be the drug of choice for streptococcal pharyngitis, although failure rates of up to 20% have been reported. One of possible explanations for penicillin treatment failure is presence of other species of bacteria in the normal oropharyngeal flora that can interfere with colonization and growth of Streptococcus pyogenes and influence the development of pharyngitis. A wide variety of microorganisms, including alpha-haemolytic streptococci and anaerobic bacteria, are present within the oropharynx (table 1). The strain of alpha-haemolytic streptococci is in interference with Streptococcus pyogenes. By producing bacteriocins, they inhibit colonization and growth of Streptococcus pyogenes and assist in its eradication. Anaerobic bacteria may play a direct or indirect role in development of pharyngitis. They may be directly responsible for specific forms of pharyngitis or contribute indirectly with possibility of synergy between them and Streptococcus pyogenes. Beta-lactamase-producing aerobic and anaerobic organisms may contribute to penicillin treatment failure. By producing beta-lactamase within the tonsillar tissue, they destroy penicillin and protect streptococci from the antibacterial effect of penicillin. Pharyngeal bacterial flora may vary according to the state of the patient (Figure 1). During an acute infection and in the cases of treatment failure and recurrent pharyngitis the number of alpha-haemolytic streptococci declines, while there is an increase in the number of anaerobic and beta-lactamase-producing organisms. After successful treatment the number and type of bacteria is similar to those found within normal tissue. Knowing the distribution and changes in pharyngeal bacterial flora is important for choosing the optimal drug for treatment of streptococcal pharyngitis. Although penicillin reduces the number of interfering beta-haemolytic streptococci, because of its advantages, if remains the drug of choice for the treatment of streptococcal pharyngitis. In cases of treatment failure and recurrent infections cephalosporins and macrolides may be a useful alternative to penicillin because they possess relatively poor activity against alpha-haemolytic streptococci, resistance to beta-lactamase and because of better penetration into tonsilar tissue.     

Moraxella catarrhalis: clinical significance, antimicrobial susceptibility and BRO beta-lactamases

Moraxella catarrhalis is an important pathogen of humans. It is a common cause of respiratory infections, particularly otitis media in children and lower respiratory tract infections in the elderly. Colonisation of the upper respiratory tract appears to be associated with infection in many cases, although this association is not well understood. Nosocomial transmission is being increasingly documented and the emergence of this organism as a cause of bacteremia is of concern. The widespread production of a beta-lactamase enzyme renders Moraxella catarrhalis resistant to the penicillins. Cephalosporins and beta-lactamase inhibitor combinations are effective for treatment of beta-lactamase producers, and the organism remains nearly universally susceptible to the macrolides, fluoroquinolones, tetracyclines and the combination of trimethoprim and sulfamethoxazole. Two major beta-lactamase forms, BRO-1 and BRO-2, have been described on the basis of their isoelectric focusing patterns. The BRO-1 enzyme is found in the majority of beta-lactamase-producing isolates and confers a higher level of resistance to strains than BRO-2. The BRO enzymes are membrane associated and their production appears to be mediated by chromosomal determinants which are transmissible by an unknown mechanism. The origin of these novel proteins is unknown.     

Serious group A beta-hemolytic streptococcal infections complicating varicella

STUDY OBJECTIVE: To alert practicing emergency physicians to an important and possibly increasing relationship between life-threatening group A beta-hemolytic streptococcal (GABHS) infections and children recovering from varicella. DESIGN: A case series of six patients managed from January through March 1993. SETTING: A university-affiliated pediatric specialty emergency department. TYPE OF PARTICIPANTS: Six previously healthy immunocompetent children between 1 and 5 years of age seen in our ED over a nine-week period. RESULTS: Six children had onset of varicella two days to two weeks before developing a serious life-threatening GABHS infection. Children presented with clinical symptoms of invasive GABHS infection with bacteremia (one patient); streptococcal toxic shock syndrome with negative blood culture (two), pneumonia with pleural effusion and streptococcal toxic shock syndrome (one), pneumonia with pleural effusion (one), and pyomyositis of the thigh (one). Four of six patients required intensive care admissions and aggressive support of vital signs. All six survived. CONCLUSION: Emergency physicians should be aware of the association between varicella and serious GABHS infections and be prepared to recognize and aggressively manage serious complications should they occur.     

The management of resistance using time-out technique

A new type of fulminant group A streptococcal infection in obstetric patients is described. The illness occurs in late stage of pregnancy, and is preceded by an episode of upper respiratory tract infection. This is followed by sudden onset of septicemia, subsequent hematogenous infection of the myometrium by the bacteria, and development of acute purulent myometritis. Shock and multiorgan failure ensue rapidly. Prognosis of both the mother and fetus is very poor, as recognition of this serious condition is difficult until the late stage of the disease. This type of infection is entirely different from classical puerperal sepsis in that the illness starts before delivery, and that there was no evidence of ascending bacterial infections of the birth canal, such as acute endometritis or chorioamnionitis, in affected mothers. The underlying mechanism for this serious infection remains unknown.     

Diagnosis of bronchopulmonary infections by quantification of microflora

The quantification of bacteria and fungi in sputum or bronchoaspirate is of clinical value for the diagnosis of respiratory tract infections. We have developed an easy method to count the micro-organisms in patients with respiratory tract infections. This consists of the quantification of micro-organisms by subsequent streakings of a calibrated loop on agar. The correlation between microbiological quantitative data and the clinical status of patients with lower respiratory tract infections is discussed. The data seem to indicate that certain bacteria present in sputum or bronchoaspirate above a certain concentration may be responsible for lower respiratory tract infections. In patients with immunological disorders or chronic pathologies even lower concentrations of micro-organisms in bronchial secretions probably are enough to cause infections. The advantage of this counting method of the microbic species from the respiratory tract consists of their quantification: thus we can attribute an etiological role to a high concentration of the germs, while micro-organisms at low concentrations are probably contaminants. By this method isolated colonies are obtained after 12-18 hours. The bacterial quantification, by respiratory samples examination of the same patient in the following days, allows us to evaluate the efficacy of antibacterial therapy, producing a reduction of bacterial concentration.     

Is Streptococcus pneumoniae a nosocomially acquired pathogen?

Streptococcus pneumoniae is most prominently a major cause of community-acquired infections of the respiratory tract, central nervous system, and bloodstream, but there is an increasing interest in its role in the epidemiology of hospital-acquired infections. Penicillin-resistant pneumococcal strains appeared 3 decades ago and now are present worldwide, often displaying multiple resistance due to antibiotic selective pressure. Horizontal spread can cause either sporadic cases or hospital outbreaks, primarily in younger children and elderly patients. Pneumococcal transmission from one patient to another can be documented by polymerase chain reaction or pulsed-field gel electrophoresis typing. Nosocomial acquisition of infection, along with pediatric age, previous hospitalization, and previous beta-lactam therapy, are the main risk factors significantly associated with penicillin-resistant pneumococcal infections. Nosocomial acquisition also is associated with higher mortality from pneumococcal disease. The importance of penicillin resistance as a risk factor significantly associated with higher mortality from pneumococcal infection is found in some studies, but not in others. Mortality from pneumococcal pneumonia is approximately the same for human immunodeficiency virus (HIV)-infected patients without acquired immunodeficiency syndrome (AIDS) as for HIV-negative subjects, but it is significantly higher in AIDS patients. Penicillin-resistant strains are involved in the vast majority of hospital outbreaks, whether presenting as clinically manifest infection or a simple colonization. Pneumococcal vaccination is recommended universally in order to lower the incidence of invasive infection, although a number of problems can limit its effectiveness.     

The role of anaerobic bacteria in recurrent episodes of sinusitis and tonsillitis

Chronic and recurrent upper respiratory tract infections represent a significant clinical challenge. The causative organisms tend to be heterogeneous, involving both aerobes and gram-positive and gram-negative anaerobes. There is evidence that these mixed groups of bacteria interact synergistically, enhancing and prolonging the overall virulence of infection. The role of anaerobic bacteria, in particular their proposed ability to protect susceptible organisms by the production of beta-lactamases, has been the subject of intense speculation. The evidence of a significant role for anaerobic bacteria in recurrent episodes of tonsillitis and sinusitis is reviewed and the most appropriate antimicrobial strategies and possible future developments in diagnosis and therapy are discussed.     

Azithromycin. A review of its use in paediatric infectious diseases

Azithromycin is an azalide antimicrobial agent active in vitro against major pathogens responsible for infections of the respiratory tract, skin and soft tissues in children. Pathogens that are generally susceptible to azithromycin include Haemophilus influenzae (including ampicillin-resistant strains), Moraxella catarrhalis, Chlamydia pneumoniae, Chlamydia trachomatis, Mycoplasma pneumoniae, Legionella spp., Streptococcus pyogenes and Streptococcus agalactiae. Azithromycin is also generally active against erythromycin- and penicillin-susceptible Streptococcus pneumoniae and methicillin-susceptible Staphylococcus aureus. Azithromycin is administered once daily, achieves clinically relevant concentrations at sites of infection, is slowly eliminated from the body and has few drug interactions. In children, azithromycin is usually given as either a 3-day course of 10 mg/kg/day or a 5-day course with 10 mg/kg on the first day, followed by 5 mg/kg/day for a further 4 days. These standard regimens were as effective as amoxicillin/clavulanic acid, clarithromycin, cefaclor and amoxicillin in the treatment of children with otitis media. Azithromycin was also as effective as either phenoxymethylpenicillin (penicillin V), erythromycin, clarithromycin or cefaclor against streptococcal pharyngitis or tonsillitis in children, but appears to result in more recurrence of infection than phenoxymethylpenicillin in this indication, necessitating a dosage of 12 mg/kg/day for 5 days. Community-acquired pneumonia, bronchitis and other respiratory tract infections in children responded as well to azithromycin as to amoxicillin/clavulanic acid, cefaclor, erythromycin or josamycin. Azithromycin was similar or superior to ceftibuten in mixed general practice populations of patients. However, symptoms of lower respiratory tract infections resolved more rapidly with azithromycin than with erythromycin, josamycin or cefaclor. Skin and soft tissue infections responded as well to azithromycin as to cefaclor, dicloxacillin or flucloxacillin, and oral azithromycin was as effective as ocular tetracycline in treating trachoma. Although not as well tolerated as phenoxymethylpenicillin in the treatment of streptococcal pharyngitis, azithromycin is at least as well tolerated as most other agents used to treat respiratory tract and other infections in children and was better tolerated than amoxicillin/clavulanic acid. Adverse events that do occur are mostly gastrointestinal and tend to be mild to moderate in severity. CONCLUSIONS: Azithromycin is an effective and well tolerated alternative to first-line agents in the treatment of respiratory tract, skin and soft tissue infections in children, offerring the convenience of a short, once-daily regimen.     

The beta-lactamases of Moraxella (Branhamella) catarrhalis isolated from Danish children

Two distinct beta-lactamases have been isolated from Moraxella catarrhalis: the stronger acting BRO-1 enzyme and the weaker acting BRO-2. Several reports have noted an effect of penicillin and ampicillin on infections caused by M. catarrhalis in spite of the presence of beta-lactamase production. The purpose of this work was to charaterize the beta-lactamases of M. catarrhalis isolated from Danish children regarding type and susceptibility, and to relate these findings to the eradication of beta-lactamases-producing strains by use of antibiotic treatment with penicillin or ampicillin. MICs for penicillin V, ampicillin, cefuroxime and amoxicillin/clavulanic acid (2:1) were determined in 70 strains of M. catarrhalis: 46 strains from children with lower respiratory tract infection (LRTI) and 24 strains from respiratory healthy children, beta-lactamase production was found in 59 strains. The BRO-1 enzyme was identified by isoelectric focusing in 55 strains (93.2%) and BRO-2 in 3 strains (5.1%); in 1 strain no isoelectric bands were produced. All strains were susceptible to cefuroxime and amoxicillin/clavulanic acid, and non-beta-lactamase-producing strains were susceptible to penicillin and ampicillin. For the beta-lactamase-producing strains, MIC50 of penicillin was 8.0 micrograms/ml, while MIC50 of ampicillin was 1.0 microgram/ml and MIC90 of ampicillin was 2.0 micrograms/ml. M. catarrhalis was more often eradicated from the children who received antibiotic treatment with penicillin or ampicillin than from those who did not receive any treatment, indicating an in vivo effect of penicillin and ampicillin in spite of the beta-lactamase production.     

Experimental evidence for Moraxella-induced penicillin neutralization in pneumococcal pneumonia

Resistance of microorganisms to antimicrobial agents is an increasing problem in the treatment of infectious diseases. In mixed infections, an interesting development can arise when one organism protects another from being killed by an antibiotic. Unfortunately, in the case of respiratory tract infections, experimental evidence of this development is poor. In this study, mice intranasally infected with a lethal number of pneumococci and treated with a curative dose of penicillin or amoxicillin died from pneumococcal pneumonia when they were coinoculated with beta-lactamase-producing Moraxella catarrhalis. beta-lactamase-negative M. catarrhalis did not show a similar indirect pathogenic effect. Treatment with a combination of amoxicillin and the beta-lactamase inhibitor clavulanic acid was not affected by beta-lactamase-producing M. catarrhalis. These findings help explain antibiotic failure in respiratory tract infections, even though the causative microorganism is sensitive to the antibiotic in vitro.     

Acute exacerbation following bronchoalveolar lavage in idiopathic interstitial pneumonia

We report two cases of idiopathic interstitial pneumonia (IIP) with acute deterioration after bronchoalveolar lavage (BAL). Case 1 was a 54-year-old woman, and case 2 was a 75-year-old man. Both were diagnosed as having IIP, and hospitalized with complaints of high fever and dyspnea. After BAL, the degree of dyspnea increased. White blood cell count and lactate dehydrogenase were elevated, and PaO2 was decreased. Chest X-ray revealed consolidation of the upper lung fields and reticulo-granular shadows spreading through both lungs. BAL fluid examination showed an elevated neutrophil fraction (case 1: 6.5%, case 2: 35.2%), suggesting respiratory tract infection although bacteria could not be detected. Case 1 died of respiratory failure despite corticosteroid therapy. Autopsy revealed diffuse alveolar damage with focal pneumonia in the right S6 corresponding to the upper lobe consolidation. Case 2 improved after antibiotic therapy. These findings suggest that aspiration of infected fluid during BAL can cause acute exacerbation of IIP. It is important to recognize that the BAL procedure can induce an acute exacerbation of IIP.     

Iodine-123-BMIPP myocardial washout and cardiac work during exercise in normal and ischemic hearts

Due to the changes in the frequency of penicillin-resistant strains of S. pneumoniae, it is necessary to perform surveillance studies of bacterial resistance. Isolates from the upper respiratory tract of asymptomatic children have been useful. There is no information about the difference between isolates from children with and without upper respiratory tract infection (URTI). The objective of the authors in this paper is to establish the prevalence of carrier-state, serotype and antimicrobial resistance of S. pneumoniae isolates from children with and without acute upper respiratory tract infection (URTI) in a rural area in Mexico. A cross-sectional comparative study was performed in Tlaxcala, Mexico. Children from one month 5 years of age were included. Nasopharyngeal swabs were obtained. Identification was done by international microbiology standards. Serotyping was done by the capsular Quellung test. The susceptibility testing was performed by the agar dilution method. Four-hundred and fifty patients were included. S. pneumoniae was isolated in 134 children (29.7%). Frequency of carriers was greater in patients with URTI (107/323) than without URTI (27/127) (33.1% vs. 21.1% p = 0.012, OR 1.84, IC 95% 1.1-3.08). The six most frequent serotypes were: 6B (16.4%); 19F (11.9%); 19A (6.7%); 14, 23F, and 35 (5.2% each), with no difference among the groups. Only 3% of the strains had high level resistance to penicillin, and 12.6% had intermediate resistance, and for ampicillin 4%, amoxicillin 4%, amoxicillin-clavulanate 4%, ceftriaxone 3%, cefotaxime 1.5%, erythromycin 6%, miocamycin 3%, chloramphenicol 4%, and vancomycin 0%. Trimethoprim-sulfamethoxazole resistance was very high (42%). In conclusion, colonization is higher in children with URTI. Five of the most frequent serotypes identified in this study were the same as those identified in patients with S. pneumoniae invasive diseases in Mexico City. In Tlaxcala, Mexico, beta-lactams could be the drug of choice for the treatment of S. pneumoniae lower respiratory tract infections. It is necessary to perform clinical assays to evaluate the efficacy of trimethoprim-sulfamethoxazole due to the high resistance in vitro.     

Pasteurella multocida tonsillitis: case report and review

Pasteurella multocida is frequently part of the normal flora of the nasopharynx and digestive tract of several wild and domestic animals. Although P. multocida can produce a variety of upper and lower respiratory tract infections, only four previous cases of tonsillitis caused by this organism have been reported. We present a case of pasteurella tonsillitis in a 30-year-old female who was exposed through her cat, which manifested upper respiratory symptoms.     

Bacteremia with granulocytopenia--microbiology and empiric antibiotic treatment

This article sums up a retrospective analysis of 84 episodes of bacteraemia in acute leukaemia patients with severe neutropenia in a Norwegian teaching hospital during the period 1990-95. Gram negative bacteria represented 54% of the blood culture isolates, all of which were susceptible to aminoglycosides, and nearly all to ceftazidime and imipenem. Penicillin/aminoglycoside was used as initial therapy in 43% of the episodes. Initial empiric therapy was modified in 52% of the events. Only 15% of patients receiving the penicillin/aminoglycoside combination actually had infections with organisms susceptible to penicillin. Only 2% of patients with gram negative infections received initial synergistic treatment with two effective drugs. Mortality from infections was 8% in acute leukaemia patients with documented bacteraemia. Deaths mainly occurred in patients with terminal leukaemia disease. Late breakthrough bacteraemias with Stenotrophomonas maltophilia and Pseudomonas aeruginosa caused 50% of all fatal infections. The analysis suggests that no patients died during initial bacteraemia with penicillin-resistant organisms treated with penicillin/aminoglycoside. The antibiotic susceptibility of the isolated bacteria was favourable compared to what has been found in other countries. For the time being, we believe that the ecological advantages of using penicillin/aminoglycoside as initial empiric treatment of febrile neutropenia are greater than the disadvantages.     

Bacterial colonization of the upper respiratory tract of patients with primary lung cancer and nonmalignant lung disease

We examined the bacterial colonization of the upper respiratory tract of 110 patients with primary lung cancer (PLC), 75 patients with nonmalignant lung diseases (NMLD) and 45 healthy volunteers (HV), comparing the sensitivity of expectorated sputum, and throat and nasal swabs. The frequency of bacterial colonization of the upper respiratory tract was significantly higher in the PLC patients (59.1%) than in NMLD patients (37.3%, p < 0.01) and HV (37.8%, p < 0.01). The frequency of gram-negative colonization was significantly higher in PLC patients than in the other subjects (p < 0.01). Expectorated sputum and nasal swab were the most sensitive for detection of whole bacteria and methicillin-resistant Staphylococcus aureus in the patients with PLC. Our results showed that PLC patients are significantly more frequently colonized by bacteria in their upper respiratory tracts and that a combination culture of expectorated sputum and nasal swab is suitable to estimate the bacterial colonization of the upper respiratory tract in the patients.     

Rapid increase of pneumococcal resistance to beta-lactam and other antibiotics in isolates from the respiratory tract (Nagasaki, Japan: 1975-1994)

The susceptibility of 101 pneumococcal isolates from the respiratory tract during 1991-1994 was examined and compared with the susceptibility of isolates over the period of 1975-1990. A rapid increase of resistance was seen not only to penicillin but also other antimicrobial agents. During 1991-1994, 38% of all the isolates were resistant to penicillin. The rates of resistance during this period were 16-23% for three newer cephalosporins, 18% for imipenem, 69% for tetracycline, 31% for erythromycin, 20% for chloramphenicol and 9% for clindamycin. The use of antibiotics within one month prior to pneumococcal isolation was correlated with penicillin resistance (P < 0.05). Serotyping of the isolates by antiserum revealed differences in predominant types between penicillin-resistant (19F, 23F,4) and -susceptible isolates (15, 4, 11A). Our data suggests that anti-pneumococcal antibiotics should be carefully chosen on the basis of susceptibility tests.     

Importance of streptococci as pathogens in the urinary tract

Streptococcus faecalis, while the most common streptococcal serotype causing urinary tract infection, is not the only one. Lancefield group A, B, C and G serotypes are capable of invading the urinary tract. This finding is not generally appreciated. The reason for this anomaly is seen in the failure of most investigators to utilise a definitive procedure to group streptococcal isolates from urine. Streptococci are responsible for 8.5 percent of urinary tract infections in this hospital.     

Effects of phospholipid base analogues on the subcellular membrane ether composition of suspension cultured LM cells

Morbidity and mortality from pulmonary complications following urinary tract operations can be reduced by preoperative identification of the high risk patient. Pulmonary function tests and arterial blood gases are necessary to identify these patients and to delineate the severity of their pulmonary disease. Respiratory complications can be prevented in many patients with the proper use of pre- and postoperative chest physical therapy and oxygen therapy. Despite the most careful pulmonary management, some patients develop acute respiratory failure following urologic operations. Respiratory failure results from a combination of physiologic abnormalities which impair alveolar ventilation and oxygenation. Utilizing controlled ventilation, supplemental oxygen, and a physiologic approach to treating the underlying cause of respiratory failure, three fourths of urologic patients in respiratory failure may be expected to survive.