Significant reduction of methicillin-resistant Staphylococcus aureus bacteremia in geriatric wards after introduction of infection control measures against nosocomial infections.

OBJECTIVES: (1) To investigate the efficacy of infection control measures against methicillin-resistant Staphylococcus aureus (MRSA) bacteremias in geriatric wards. (2) To identify predisposing risk factors for MRSA bacteremia. METHODS: Cases with nosocomial bacteremias were retrospectively analyzed between January 1991 and March 1995. The study period was divided into four annual periods and the period 1, January to December 1991, was applied as the control. MATERIALS: We investigated patients with nosocomial bacteremias in geriatric wards (190 beds) of AINO Memorial Hospital, affiliated with Nagasaki University. RESULTS: A significant reduction in cases with MRSA-induced nosocomial bacteremia was observed after the introduction of a stringent infection control and prevention program (period 1 vs. periods 2, 3, and 4: p<0.00833, p<0.00167, and p<0.00167, respectively). The major source of bacteremia included urinary tract infections, intravenous catheter-related infections, and infected decubitus ulcers. Improvement of decubitus ulcer was associated with a significant reduction in MRSA bacteremia (period 1 vs. periods 2 and 3: p<0.00017 and p<0.00833). CONCLUSION: Stringent infection control programs, including prevention and treatment of decubitus ulcers, are necessary in geriatric wards to reduce and prevent MRSA bacteremia.

A comparative clinical study of pneumonia by penicillin-resistant and -sensitive Streptococcus pneumoniae in a community hospital.

OBJECTIVE: This study aimed to determine the clinical difference of pneumonia between penicillin-resistant and penicillin-sensitive Streptococcus pneumoniae. METHODOLOGY: Forty-nine cases in 46 patients of pneumococcal pneumonia were studied from December 1992 to May 1997. There were 24 cases (in 22 patients) of penicillin-resistant pneumococci (PRSP) pneumonia which were compared with 25 cases (in 24 patients) with penicillin-sensitive pneumococci (PSSP). RESULTS: Both the mean age and the underlying disease states did not differ between the two groups. However, hospital-acquired pneumonia and previous use of antibiotics were observed in eight (33.3%) and 12 (50.0%) patients in PRSP compared with three (12.0%) and two (8.0%) in PSSP, respectively. The clinical efficacy rate and bacteriological eradication rates were 87.5 and 87.5% in PRSP compared with 87.5 and 87.0% in PSSP, respectively. Minimum inhibitory concentration (MIC) of antibiotics against 30 pneumococcal isolates was examined, and 10 strains ranged from 0.10-0.78 microg/mL and five strains were more than 1.56 microg/mL against penicillin G, while the MIC showed higher resistance to other antibiotics except for the carbapenems. Serotyping of the isolates by antiserum revealed differences in the predominant types PRSP (19F) and PSSP (6A,9V) [corrected]. CONCLUSIONS: We must care for not only community-acquired infection but also nosocomial transmission of PRSP pneumonia. Most patients with infections due to PRSP tended to have a milder illness with a good outcome (no patient died). As such it appears that empiric therapy for pneumococcal pneumonia does not require modification from what is recommended at present. However, in patients with infection due to highly resistant strains, and who are not responding to conventional therapy should have their treatment modified according to subsequent susceptibility testing.

The effects of S-carboxymethylcysteine and N-acetylcysteine on the adherence of Moraxella catarrhalis to human pharyngeal epithelial cells.

We investigated the effects of two mucoregulating drugs, S-carboxymethylcysteine (S-CMC) and N-acetylcysteine (NAC), on the attachment of Moraxella catarrhalis (M. catarrhalis) to pharyngeal epithelial cells. The attachment of M. catarrhalis decreased (33-57%) significantly (P<0.01) in a dose-dependent manner in cells treated with mucoregulating drugs as compared to the control. There was a significant (P<0.01) decrease (35-45%) in the attachment of M. catarrhalis to pharyngeal cells after oral administration of S-CMC. By electron microscopic observation, it was found that there was a fine, granular, electron-dense, ruthenium red-positive layer on the surface of pharyngeal epithelial cells; this layer was absent on cell surfaces treated with mucoregulating drugs. Possibly, this layer contained the portion of M. catarrhalis receptor which is responsible for the attachment of this bacteria to pharyngeal epithelial cells. From the above results, it may be concluded that one of the mechanisms of mucoregulating drugs to decrease the episode of respiratory infections in patients with chronic respiratory diseases is by inhibiting the attachment of bacteria to the upper respiratory tract.

Antimicrobial resistance and serotype distribution of Streptococcus pneumoniae strains causing childhood infections in Bangladesh, 1993 to 1997.

Three hundred sixty-two Streptococcus pneumoniae strains were isolated from children under 5 years of age at Dhaka Shishu (Children) Hospital from 1993 to 1997. The strains were isolated from blood (n = 105), CSF (n = 164), ear swab (n = 61), eye swab (n = 20), and pus (n = 12). Of the 362 isolates, 42 (11.6%) showed intermediate resistance (MIC, <0.1 microgram/ml) and only 4 (1.1%) showed complete resistance (MIC, >2.0 microgram/ml) to penicillin. Penicillin resistance exhibited a strong relationship with serotype 14; 47.8% of the penicillin-resistant strains belonged to this type. A remarkably high (64.1%) resistance to co-trimoxazole was observed, along with a significant increase during the time period studied; there was no relationship to capsular type. By way of contrast, penicillin resistance did not show any significant change during the study period. Resistance to chloramphenicol (2.2%) and erythromycin (1.1%) was rare. The high resistance to co-trimoxazole and its increasing trend demand elucidation of the clinical impact of pneumonia treatment by this antimicrobial and reconsideration of the World Health Organization recommendation for co-trimoxazole administration to children with community-acquired pneumonia at the health care worker level in Bangladesh.

Attachment of nontypable Haemophilus influenzae to human pharyngeal epithelial cells mediated by a ganglioside receptor.

Nontypable Haemophilus influenzae (NTHI) is one of the major pathogens of human respiratory infections and has the ability to attach to pharyngeal epithelial cells. We characterized the epithelial cell receptor to which NTHI bind. Neuraminidase pretreatment of pharyngeal epithelial cells resulted in a significant decrease in NTHI attachment, suggesting sialic acid as an important component of the receptor. The attachment was not decreased in NTHI pretreated with 1,000 microg/ml of fucose, N-acetyl-neuraminic acid, N-acetyl-glucosamine, N-acetyl-galactosamine, acetyl-salicylic acid and colominic acid. Only treatment with gangliosides D1a, D1b and D2 at a concentration of 12.5 microg/ml significantly decreased the attachment. On the other hand, treatment with gangliosides M1, M2, M3, D3, T1b and asialoganglioside M1 did not decrease the attachment of NTHI. Only ganglioside D2 inhibited the attachment significantly at a concentration of 12.5 ng/ml. Other isolates of NTHI showed a decrease in attachment after treatment with ganglioside D2. Treatment of cells with anti-human GD2 monoclonal antibody also decreased the attachment of NTHI in a dose-dependent manner. This study indicates that sialic acid glycoconjugate, GD2, is one of the receptors of NTHI on human pharyngeal epithelial cells.

[Clinical study of MRSA carrier in sputum].

We studied the clinical aspects of 25 patients (17 male, 8 female, median age 79.4 y.o.) whom MRSA was colonized in sputum from 1989 January to 1994 December. Main underlying diseases were 16 chronic bronchitis and 15 Cerebrovascular damage. Nineteen cases (76%) had catheters, for example 15 urinary tract catheters and 8 nasogastric tube. Twenty-two cases (88%) used previous antimicrobial agent. Fifteen cases (60%) were dead during previous period, and that 14 cases were dead because of respiratory failure within a year after MRSA was colonized in sputum. Nine cases (36%) were able to remove MRSA in sputum, but mortality rate was not different whether MRSA disappear or continue, MIC50 against MRSA (19 strains) were minocycline 12.5 micrograms/ml, arbekacin 6.25 micrograms/ml, vancomycin 0.78 microgram/ml and 16 cases (84.2%) were coagulase type II.

Isolation of pathogenic bacteria from induced sputum from hospitalized children with pneumonia in Bangladesh.

A prospective study was carried out on 157 patients admitted to a paediatric hospital in Dhaka, Bangladesh to determine the bacteria present in the induced sputum of paediatric patients with X-ray proven pneumonia. Their ages ranged from 21 days to 11 years; 65 per cent of them were male and 35 per cent were female. The most affected age group was between 6 months and 2 years old. Respiratory secretions produced by induced cough were taken by swab from the oropharynx for culture and smear. The predominant bacteria were Haemophilus influenzae, Streptococcus pneumoniae, Branhamella catarrhalis and Gram-negative bacilli. Serotyping of H. influenzae revealed that 76 per cent were non-typable and 18 per cent were of type b; 23.5 per cent of isolates of H. influenzae were beta-lactamase producing. MIC90 of penicillin against S. pneumoniae and H. influenzae were 0.025 and 3.13 micrograms/ml respectively. Ampicillin, penicillin G (benzylpenicillin), amoxycillin, and gentamicin were administered for the treatment of these patients. All cases were apparently improved, on the basis of clinical evaluation, and discharged from the hospital.

[Coagulase typing of Staphylococcus aureus in the geriatric wards after introduction of preventive measures of hospital infection].

In the early 1980's methicillin-resistant Staphylococcus aureus (MRSA) was reported as a major pathogenic organism of geriatric hospital infection in Japan. At the same time in our geriatric wards, including 190 beds, MRSA infection was prevalent. In the early 1980's in our geriatric wards minocycline was one of the most sensitive antibiotics to MRSA isolated in our wards and used frequently against MRSA pneumonias and bacteremia. In the late 1980's resistant strains of MRSA to minocycline rapidly increased because vancomycin was not allowed to introduced for treatment of MRSA before 1991 in Japan. At the same period the predominant coagulase type changed from type II to type VII. To decrease minocycline-resistant strains to MRSA after 1987, use of minocycline was limited. Moreover since Oct. 1991 to decrease nosocomial infections some active preventive measures against hospital infection, including limited use of 2nd and 3rd cephems, were taken. In this study changing patterns of coagulase type of Staphylococcus aureus were discussed. At least 4 years was needed to find out that the predominant coagulase type changed from type VII to type II again in 1991. In this study about 22 antimicrobial agents MICs of 313 strains of Staphylococcus aureus isolated between March 1992 and June 1993 were determined and compared with the data of MICs before introduction of preventive measures. The pattern of susceptibility to MINO was in part improved. Thus the some sensitive strains of S. aureus were observed again in our geriatric wards. Interestingly indeed it took approximately 5 years to find out the emergence of sensitive strains to MINO since limitation of use of MINO in 1987.

Serotypes of Streptococcus pneumoniae causing invasive childhood infections in Bangladesh, 1992 to 1995.

One hundred sixty-five invasive Streptococcus pneumoniae strains were isolated from children under five at Dhaka Shishu (Children's) Hospital during the period 1992 to 1995. Ninety-four strains were from cerebrospinal fluid, and 71 were from blood. More than 91% of the strains were isolated from patients aged 24 months or less. Predominant serotypes were, in descending order 7F, 12F, 14, 15B, 18, 5, and 22A. These comprised 70% of all isolates. The marked differences in serotype distribution in different countries indicate the need for a sentinel surveillance study for the countries of South Asia, particularly Bangladesh, China, India, and Pakistan.

The increasing burden of disease in Bangladeshi children due to Haemophilus influenzae type b meningitis.

A laboratory-based study of diagnosed bacterial meningitis in the national paediatric hospital identified 852 cases of meningitis in the 8-year period 1987-1994. There were 587 culture-positive cases, of which Haemophilus influenzae (47%) and Streptococcus pneumoniae (32%) accounted for 80%. H. influenzae showed a remarkable increase of 700% during the study period. Most of the H. influenzae cases (90%) occurred in the 1st 2 years of life. Analysis of culture-negative specimens by antigen detection in the last 2 years also revealed the predominance of H. influenzae (71.4%) and S. pneumoniae (22.4%). Typing of H. influenzae isolates during this time showed that 98% of the strains were type b. This retrospective hospital-based study indicated a pronounced increase in the incidence of H. influenzae meningitis and strongly supports the need for large-scale Hib vaccination for young children. However, such nationwide intervention will probably need to be based on a prospective on a prospective and population-based surveillance of H. influenzae infections.

[A clinical study of skin flora in patients with MRSA colonization after introduction of preventive measures of hospital infection in a geriatric ward].

In early 1980's methicillin-resistant Staphylococcus aureus (MRSA) was reported as a major pathogenic organism of geriatric hospital infection in Japan. At the same time in the geriatric hospital MRSA infection was prevalent. To decrease nosocomial infections some active preventive measures against hospital infection were taken since Oct. 1991. After introduction of preventive measures of hospital infection in the geriatric ward (190 beds) nosocomial bacteremia and pneumonia were markedly decreased in comparison of episode number before introduction of prevention. However several patients with MRSA colonization were observed every month. The aim of this clinical study was to clear how frequent MRSA was isolated from skin. Consequently 3 strains (3.4%) of MRSA were observed in 86 cultured skin. In conclusion we considered frequency of MRSA colonization frequency of MRSA colonization on skin was not so high but rather very low under the preventive measures.

Moraxella (Branhamella) catarrhalis adherence to human bronchial and oropharyngeal cells: the role of adherence in lower respiratory tract infections.

To study the role of Moraxella (subgenus Branhamella) catarrhalis (B. catarrhalis) adherence to airway cells in lower respiratory tract infections, the in vitro attachments of B. catarrhalis to upper airway (oropharyngeal) and lower airway (bronchial) epithelial cells were compared. The adherence of 4 strains (1 nonfimbriated and 3 fimbriated) of B. catarrhalis to respiratory tract epithelial cells collected from 11 patients with chronic pulmonary disease (CPD) and 11 healthy individuals was evaluated. Both the fimbriated and nonfimbriated strains showed increased attachment to oropharyngeal cells in the CPD patients (mean +/- SEM; 25.0 +/- 3.2/cell; P < 0.01) when compared to the control subjects (12.1 +/- 1.1/cell). On the average, the attachment to bronchial cells was 6.1 to 13.6 times greater per surface area (bacteria/micron2) than the attachment to oropharyngeal cells. The fimbriated strains tended to adhere in higher numbers to bronchial cells (19.0 +/- 1.8/cell) than the nonfimbriated strain (8.7 +/- 1.2/cell), although there was no difference between the CPD and control groups. In conclusion, the attachment of B. catarrhalis to oropharyngeal cells may be an enhancing factor for colonization in the upper respiratory tract in patients with CPD, and elevated adherence of the bacteria to bronchial cells may suggest pathogenic importance when mucociliary function is impaired.

[A case of pseudomembranous enterocolitis which diagnosis was delayed in the outpatient clinic].

A 71-year-old male visited our hospital because of diarrhea. At first we suspected infectious colitis and levofloxacin (300 mg/day) was administered for four days. But the diarrhea continued, so performed a barium enema after about 3 weeks from onset. Round polyposis from the rectum to the sigmoid colon were found. Colonoscopy was suggested to the patient, but was rejected. However diarrhea continued and fever appeared. Ceftriaxone (1 g/day) and sparfloxacin (200 mg/day) were administered, but the symptoms increased. He was admitted about 6 weeks from onset, and the colonoscopy showed multiple round yellow-white pseudomembranes. Pseudomembranous enterocolitis diagnosed because Clostridium difficile and its toxin were positive in the feces. After oral administration of vancomycin (1.5 g/day) was started, the symptoms alleviated rapidly and disappearance of pseudomembrane was confirmed by colonoscopy.

[Clinical study of 18 patients whom MRSA was detected from stool--especially about comparison enterocolitis with colonization].

We studied the clinical aspects of 18 patients from whom MRSA was detected from the stool and compared with 9 enterocolitis cases (7 male, 2 female, median age 72.4 y.o.) with 9 colonization cases (5 male, 4 female, median age 70.2 y.o.) from 1991 June to 1995 May. Cases of postoperative, use of anti-peptic ulcer drugs and administration of antibiotics for enterocolitis were more than that of colonization. On the other hand, eatable patients in the colonization group who could take food orally were more in number. Many patients of both enterocolitis and colonization were colonized in the respiratory tract. Drug sensitivity of MRSA in both cases were almost the same and the coagulase type were all that of II. Three courses on how MRSA enterocolitis occurs is considered. At first, colonization in the respiratory tract, second, proliferation of MRSA in the higher pH gastric juices as a result of gastrectomy or use of anti-peptic ulcer drugs, and third, selection of MRSA after administration of antibiotics.

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.

Attachment of Moraxella catarrhalis to pharyngeal epithelial cells is mediated by a glycosphingolipid receptor.

Moraxella catarrhalis is one of the major pathogens of respiratory infections and has the ability to attach to the pharyngeal cells iva fimbriae. We characterized the epithelial cell receptor to which fimbriate M. catarrhalis binds. Neuraminidase pretreatment of pharyngeal epithelial cells resulted in a significant decrease of M. catarrhalis attachment, suggesting interaction with the sialic acid component. The attachment was not decreased in M. catarrhalis pretreated with 2 and 1 mg/ml of fucose, N-acetyl-neuraminic acid, N-acetyl-glucosamine, N-acetyl-galactosamine, acetyl-salicylic acid and colominic acid. However, M. catarrhalis treated with gangliosides M1, M2, D1a, D1b and T1a at a concentration of 2.5 micrograms/ml had significantly decreased the attachment compared to the control. In contrast treatment with gangliosides M3 and asialoganglioside M1 did not decrease the attachment of M. catarrhalis and thereby provided evidence for specificity of the inhibition. Concentration dependent effects of ganglioside M2 on the attachment were also observed. Other fimbriate isolates of M. catarrhalis showed decrease in attachment after treatment with ganglioside M2. However there was no effect on attachment when a nonfimbriate isolate was treated with ganglioside M2. This study indicates that the receptor of fimbriate M. catarrhalis on pharyngeal epithelial cells resides in the sequences of ganglioside M2.