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Chemotherapy of systemic murine infection due to beta-lactam antibiotic 'tolerant' and non-'tolerant' Staphylococcus aureus.

Two in vitro beta-lactam antibiotic (oxacillin, cefotaxime) 'tolerant' (MBC:MIC ratios = greater than 32) strains of Staphylococcus aureus served to intraperitoneally infect cyclophosphamide-pretreated (leukopenic) NMRI mice. With larger bacterial inocula (approximately 5 X 10(8) CFU) neither oxacillin nor gentamicin or netilmicin yielded optimal chemotherapeutic results. Only combination chemotherapy, in particular oxacillin combined with netilmicin, consistently reduced mouse mortality significantly (p less than 0.001). In contrast, moderate 'tolerant' staphylococcal inocula (approximately 2 X 10(8) CFU) were amenable to chemotherapy with either oxacillin or netilmicin, but not with cefotaxime or gentamicin. Oxacillin combined with either gentamicin or netilmicin resulted in significantly lowered murine mortality rates (p less than 0.001). Cefotaxime combined with either aminoglycoside antibiotic gave less satisfactory results. Systemic murine infections due to three non-'tolerant' strains of S. aureus were amenable to chemotherapy with oxacillin, cefotaxime or netilmicin alone and to combination chemotherapy. It is recommended that cases of life-threatening S. aureus infection, not complicated by acute endocarditis, initially be treated with oxacillin plus netilmicin until availability of laboratory results (antibiogram, documentation of 'tolerance').

Animals↗

[Treatment of urinary tract infections caused by unknown bacteria (author's transl)].

The treatment of acute febrile urinary tract infections in urological patients has to start in most cases without knowledge of bacteria and their sensitivity. The results of 2,000 antibiograms and clinical observations showed good efficiency in initial therapy if combined treatment with gentamycin and cephalothin was used. Using recommeneded doses in permanent control of serum creatinine and blood-urea nitrogen, no decrease of renal function was observed in 131 patients treated with this combined therapy.

Bacteria↗

Treatment of bacterial infections of the female urinary tract by immunization of the patients.

In an open comparative study 400 patients with urinary tract infections were randomly allocated to two treatment groups. In 202 patients an immune stimulation against uropathogenic bacteria was produced with a new preparation, SolcoUrovac, and only in exceptional cases with pronounced symptomatology was antibiotic therapy given, while in the control group (n = 198) all patients were treated with nitrofurantoin or with another appropriate antibiotic, according to the antibiogram. In the subsequent 12-month observation period 28 infections occurred in 23 patients of the immune-stimulated group and 84 in 47 patients of the control group. This difference is statistically significant (p less than or equal to 0.001). The preventive effect of the SolcoUrovac therapy was particularly impressive in patients with recurrent urinary tract infections. Thirty-two patients from each group with similar case histories, as matched pairs, were evaluated separately. The relapse rate in the 12-month observation period amounted to 2 re-infections in the group treated with immunotherapy and to 29 in the control group. All side-effects were recorded. No adverse effects were observed in pregnant women or in their offspring.

Bacterial Infections↗

Spectrum of bacterial pathogens in uncomplicated and complicated urinary tract infections.

The spectra of bacterial organisms of urinary tract infections (UTI) in patients with and without abnormalities in the urinary tract (complicated and uncomplicated UTIs) are compared. Data from the United Kingdom and the Federal Republic of Germany are included. In addition, the susceptibility of the pathogens to antibiotics (for oral or parenteral application) in both countries are compared. In conclusion, rational antibiotic therapy of complicated UTIs should strictly follow the antibiogram of the causative organism. For therapy of uncomplicated UTIs, the regional state of antibiotic susceptibility of the pathogens according to geographical location should be considered and kept up to date.

Escherichia coli Infections↗

Detection of a widespread clone of Pseudomonas aeruginosa in a pediatric cystic fibrosis clinic.

Cross-infection by Pseudomonas aeruginosa between unrelated patients with cystic fibrosis (CF) is believed to be uncommon. After detecting a genotypically identical strain of P. aeruginosa in five unrelated children with CF dying from severe lung disease, we determined its prevalence within a large CF clinic using pulsed-field gel electrophoresis and random amplified polymorphic DNA assays. The clinical status of P. aeruginosa-infected patients was also determined. Between September and December 1999, 152 patients, aged 3.9-20.7 years, provided sputum for culture. P. aeruginosa was detected in 118 children of mean (SD) age 13.5 (3.8) years. The genotyping techniques were concordant, showing that 65 (55%) infected patients carried an indistinguishable or closely related strain. No distinctive antibiogram or environmental reservoir was found. Patients with the clonal strain were more likely than those with unrelated isolates to have been hospitalized in the preceding 12 months for respiratory exacerbations. This study demonstrates extensive spread of a single, clonal strain of P. aeruginosa in a large pediatric CF clinic. Whether this strain is also more virulent than sporadic isolates remains to be determined. As transmissible strains could emerge elsewhere, other CF clinics may also need to consider molecular methods of surveillance for cross-infection.

Adolescent↗

Application of polymerase chain reaction for the correlation of Salmonella serovars recovered from greyhound feces with their diet.

The polymerase chain reaction was employed to correlate Salmonella serovars isolated from fecal material of greyhounds suffering from gastroenteritis with those isolated from the diet fed to the greyhounds prior to onset of diarrhea. Kennels around the Abilene, Kansas, area were contacted and supplied with materials needed to collect a portion of the diet each day. With the onset of diarrhea, the kennels were instructed to ship the fecal material and diet from the previous 10 days to the laboratory for testing. Forty-one fecal samples and corresponding diets were screened for Salmonella, Clostridium perfringens, Campylobacter jejuni, Staphylococcus aureus, Staphylococcus intermedius, and pathogenic (piliated) Escherichia coli by direct culture using standard procedures. The fecal material was also screened for coronavirus and parvovirus using electron microscopy. Thirty-five "normal" fecal samples were screened for all of the above mentioned microorganisms as a control. In addition, the fecal material was screened for E. coli verotoxins I and II and clostridial enterotoxins. A total of 61 Salmonella isolates were recovered from the 41 samples of feces and diet submitted for testing; 31 were recovered from the feces and 30 from the diet. Four Salmonella isolates were recovered from the normal fecal samples. Results obtained by PCR, plasmid profiles, antigenic analysis, and antibiogram profiles indicated that 16 of the 31 isolates recovered from the fecal material were the same strain as that recovered from the diet.

Animal Feed↗

Detection of Salmonella enteritidis in equine feces using the polymerase chain reaction and genus-specific oligonucleotide primers.

Salmonella was identified in feces from horses, using the polymerase chain reaction (PCR) and genus-specific oligonucleotide primers. Feces from healthy horses were determined to be culture negative and PCR negative for Salmonella. Fecal samples were inoculated with known numbers of colony-forming units (CFU) of S. enteritidis. The fecal samples were enriched overnight in tetrathionate broth, and then DNA was extracted and amplified by PCR using genus-specific primers. Sensitivity of the assay extended to 10 degrees CFU Salmonella enteritidis/g feces; sensitivity of microbiologic culture with enrichment extended to 10 degrees CFU Salmonella enteritidis/g feces. Feces that were not inoculated with S. enteritidis were negative by the PCR. Detection of salmonellae in feces was possible using the PCR within 24 hours from the time of submission of samples. Because samples were enriched, isolates were available for determining antibiograms and serologic grouping or typing.

Animals↗

Clonal spread of imipenem-resistant Pseudomonas aeruginosa in the intensive care unit of a Turkish hospital.

Pseudomonas aeruginosa may cause life-threatening infections, especially in nosocomial settings. Although carbapenems are considered as one of the most effective alternatives in antipseudomonal therapy, resistance to the carbapenem group of antibacterials is a growing problem. In the first 6 months of 1997, P. aeruginosa isolates that were resistant to almost all antipseudomonal agents including imipenem were recovered from various specimens from intensive, care unit (ICU) patients. Isolates with the same antibiogram profile caused a small outbreak in May 1997. A retrospective case-control study revealed that the major risk factors for infection/colonization with multiresistant P. aeruginosa were prolonged stay in the ICU (p<0.001), previous and lengthy imipenem usage (p<0.001 and p<0.0001, respectively), and mechanical ventilation (p<0.001). Analytical isoelectric focusing of the sonicates prepared from the isolates showed that each isolate produced 1-5 beta-lactamases, enzymes with isoelectric points (pIs) of 5.1, 6.4, 8.5-8.7 being the most prevalent. DNA macrorestriction patterns of imipenem-resistant isolates were distinct from those of the imipenem-sensitive isolates recovered from ICU patients during the same interval and from the environmental isolates (controls). Thus, our results indicate that colonized patients appear to be the major source for cross-contamination of other patients and if imipenem is selected for empirical therapy, emergence of resistant strains should be anticipated and appropriate precautions taken.

Adolescent↗

A survey of antimicrobial resistance in a tertiary referral hospital in the United Arab Emirates.

Published data on antimicrobial resistance are lacking for the United Arab Emirates (UAE). Knowledge of local patterns of resistance is essential to optimize guidelines for empirical antimicrobial treatment. Awareness of susceptibility patterns in other parts of the world may be important for determining empirical antimicrobial therapy for travelers or patients transferred from abroad. Antibiograms from unique isolates of common hospital and community bacteria are described in a tertiary referral hospital in the UAE, which had no antimicrobial restrictions and limited resources. Antimicrobial resistance rates were unpredictable and were high for Gram-negative organisms, such as Escherichia coli, Shigella sonnei, Campylobacter spp, and also Streptococcus pneumoniae. In contrast, methicillin-resistant Staphylococcus aureus (MRSA) comprised less than 5% of S. aureus isolates and glycopeptide-resistant enterococci (GRE) were not detected during the surveillance period. Our results provide data on antimicrobial resistance for the UAE and highlight the need for resources for surveillance of antimicrobial resistance.

Anti-Bacterial Agents↗

Adjuvant interferon gamma in patients with drug - resistant pulmonary tuberculosis: a pilot study.

BACKGROUND: Tuberculosis (TB) is increasing in the world and drug-resistant (DR) disease beckons new treatments. METHODS: To evaluate the action of interferon (IFN) gamma as immunoadjuvant to chemotherapy on pulmonary DR-TB patients, a pilot, open label clinical trial was carried out in the Cuban reference ward for the management of this disease. The eight subjects existing in the country at the moment received, as in-patients, 1 x 10(6) IU of recombinant human IFN gamma intramuscularly, daily for one month and then three times per week up to 6 months as adjuvant to the indicated chemotherapy, according to their antibiograms and WHO guidelines. Sputum samples collection for direct smear observation and culture as well as routine clinical and thorax radiography assessments were done monthly. RESULTS: Sputum smears and cultures became negative for acid-fast-bacilli before three months of treatment in all patients. Lesion size was reduced at the end of 6 months treatment; the lesions disappeared in one case. Clinical improvement was also evident; body mass index increased in general. Interferon gamma was well tolerated. Few adverse events were registered, mostly mild; fever and arthralgias prevailed. CONCLUSIONS: These data suggest that IFN gamma is useful and well tolerated as adjunctive therapy in patients with DR-TB. Further controlled clinical trials are encouraged.

Adjuvants, Immunologic↗

Molecular and epidemiologic analysis of a county-wide outbreak caused by Salmonella enterica subsp. enterica serovar Enteritidis traced to a bakery.

BACKGROUND: An increase in the number of attendees due to acute gastroenteritis and fever was noted at one hospital emergency room in Taiwan over a seven-day period from July to August, 2001. Molecular and epidemiological surveys were performed to trace the possible source of infection. METHODS: An epidemiological investigation was undertaken to determine the cause of the outbreak. Stool and blood samples were collected according to standard protocols per Center for Disease Control, Taiwan. Typing of the Salmonella isolates from stool, blood, and food samples was performed with serotyping, antibiotypes, and pulsed field gel electrophoresis (PFGE) following XbaI restriction enzyme digestion. RESULTS: Comparison of the number of patients with and without acute gastroenteritis (506 and 4467, respectively) during the six weeks before the outbreak week revealed a significant increase in the number of patients during the outbreak week (162 and 942, respectively) (relative risk (RR): 1.44, 95% confidence interval (CI): 1.22-1.70, P value < 0.001). During the week of the outbreak, 34 of 162 patients with gastroenteritis were positive for Salmonella, and 28 of these 34 cases reported eating the same kind of bread. In total, 28 of 34 patients who ate this bread were positive for salmonella compared to only 6 of 128 people who did not eat this bread (RR: 17.6, 95%CI 7.9-39.0, P < 0.001). These breads were produced by the same bakery and were distributed to six different traditional Chinese markets., Salmonella enterica subsp. enterica serovar Enteritidis (S. Enteritidis) was isolated from the stool samples of 28 of 32 individuals and from a recalled bread sample. All S. Enteritidis isolates were of the same antibiogram. PFGE typing revealed that all except two of the clinical isolates and the bread isolates were of the same DNA macrorestriction pattern. CONCLUSIONS: The egg-covered bread contaminated with S. Enteritidis was confirmed as the vehicle of infection. Alertness in the emergency room, surveillance by the microbiology laboratory, prompt and thorough investigation to trace the source of outbreaks, and institution of appropriate control measures provide effective control of community outbreaks.

Adolescent↗

Anti-inflammatory and antimicrobial effect of lectin from Lonchocarpus sericeus seeds in an experimental rat model of infectious peritonitis.

We have investigated the anti-inflammatory and antimicrobial effect of the lectin from Lonchocarpus sericeus seeds (LSL) in a model of infectious peritonitis in adult Wistar rats. Animals were treated with saline or LSL (10 mg kg(-1), i.v) immediately and 6 h after the induction of peritonitis via cecal ligation and single puncture. Twelve hours after surgery, animals were killed and the infectious process was monitored by total and differential count of cells from blood and peritoneal washing liquid, adenosine deaminase activity, antibiogram and the number of viable bacteria of the peritoneal cavity. LSL treatment decreased the inflammatory response evoked by the induction of peritonitis, as seen by the inhibition of neutrophil migration into peritoneal cavities, leucocytosis and reduction of adenosine deaminase activity in the peritoneal fluid. All these effects were reversed by the lectin association to N-acetyl-glucosamine. LSL in-vitro did not show any antimicrobial action, but promoted a marked decrease of the viable bacterial population in peritoneal cavities. In conclusion, LSL inhibited the inflammatory response and the bacterial colonization of infectious peritonitis in rats.

Animals↗

Closed suctioning system reduces cross-contamination between bronchial system and gastric juices.

In this prospective, randomized study, we evaluated whether a closed suctioning (CS) system (TrachCare) influences crossover contamination between bronchial system and gastric juices when compared with an open suctioning system (OS). The secondary aims were an analysis of the frequency of ventilator-associated pneumonia (VAP) and an analysis of alteration in gas exchange. Antibiograms were performed from tracheal secretions and gastric juice aspirates on Days 1 and 3 of intubation in 24 patients in a medical intensive care unit. Five cross-contaminations were observed in the OS group on Day 3 versus Day 1; the 5 strains shared common genotypes as determined by random amplification of polymorphic DNA. No cross-contaminations were seen in the CS group (P = 0.037). VAP occurred in 5 patients of the OS group but in none of the CS group patients (P = 0.037). Spao(2) decreased significantly in the OS group compared with presuctioning values--the opposite of the CS group. Whereas presuctioning values were comparable between groups, postsuctioning Spao(2) was significantly higher in the CS group. CS significantly reduced cross-contamination between bronchial system and gastric juices and reduced the incidence of VAP when compared with OS. Hypoxic phases can be reduced by the help of CS.

Aged↗

Antibiotic treatment of nude rats and its impact on the aerobic bacterial flora.

A colony of nude rats were treated with the antibiotics ampicillin, spiramycin, sulfadoxine/trimethoprim, tetracycline, lincomycin and spectinomycin over a period of 30 weeks. The rats were monitored bacteriologically during the whole treatment period and for a period of 24 weeks after the treatment. Antibiograms of each isolated microorganism were made in vitro. The primary target, Pasteurella pneumotropica, was suppressed by the treatment, but reappeared after ending the medication. Klebsiella pneumoniae subsp. pneumoniae, never observed before the use of antibiotics in the colony, became one of the most common organisms in the colony. Furthermore, this bacterium was resistant to all antibiotics tested in vitro. Also other Enterobacteriaceae and some Streptococcaceae were propagated. Only Staphylococcus aureus seemed to have been eradicated by the treatment. It is concluded, that such antibiotic treatment does not necessarily improve the microbiological quality of the rats, and that it imposes a high risk of propagating resistant bacteria.

Animals↗

Molecular typing of Neisseria gonorrhoeae from hospital and community isolates by restriction fragment length polymorphism.

Strains of Neisseria gonorrhoeae are generally characterized by auxotyping, serotyping, plasmid profile, antibiotic sensitivity and deoxyribonucleic acid (DNA) amplification fingerprinting. The aim of this study was to analyse the generation of restriction fragment length polymorphism (RFLP) patterns by BgIII digestion of total genomic DNA of N. gonorrhoeae isolated from the community (n =30) and the hospital (n =15) and to establish an association with serogrouping and antibiogram. The RFLP patterns produced by BgIII restriction digestion showed 7 different patterns among 30 community isolates and 9 different patterns among 15 hospital isolates. 66.7% of isolates belonged to serogroup WI. Penicillin resistance was observed in 46.7% of community isolates and 66.7% hospital isolates. However, penicillinase producing N. gonorrhoeae (PPNG) were lower in the community (6.6%) than in the hospital isolates (53.3%). PPNG strains were more often seen in serogroup WI. This is the first Indian report on RFLP genotype pattern in N. gonorrhoeae. We noted differences in RFLP genotypes of the community (RFLP types 1, 2, 3, 4, 5 and 7) and hospital strains (RFLP types 6 and 8), while no differences in the serogroup were observed. Ciprofloxacin resistance was 20.0% and 26.6% in the community and hospital isolates, respectively. Ceftriaxone emerges as the current drug of choice for an effective policy of antibiotic treatment of gonorrhoea through syndromic management in developing countries.

Anti-Bacterial Agents↗

A novel real-time duplex PCR assay for detecting penA and ponA genotypes in Neisseria gonorrhoeae: Comparison with phenotypes determined by the E-test.

BACKGROUND: For many years, the pathogenic bacterium Neisseria gonorrhoeae, the etiologic agent of gonorrhea, was generally susceptible to penicillin, until the emergence of resistant strains. Well-characterized genetic variations in the penicillin resistance-determining region correlate with decreased susceptibility to penicillin. At least 5 genes (penA, penB, mtrR, ponA, and penC) are involved in the chromosomally mediated resistance to this antibiotic. To date, no development of multiplex PCR assays targeting a range of gonococcal genes and variations as a means of predicting antibiotic resistance has been reported. METHODS: The aim of this study was to develop a duplex assay using DNA from isolated strains. We describe the development and evaluation on the LightCycler platform of a real-time duplex PCR assay (hybridization probe format) for rapid and specific detection of ponA and penA variations, predicting penicillin susceptibilities. RESULTS: The real-time duplex PCR assay successfully detected variations in ponA and penA genes by use of distinct melting temperatures from a total of 120 Neisseria gonorrhoeae isolates. Moreover, the variation profiles obtained with the real-time PCR and the melting analysis showed good correlation with the pattern of penicillin susceptibility generated with classical antibiograms. Nucleotide sequencing data were in complete agreement with multiplex assay results. CONCLUSIONS: The presented assay is suitable for the detection of chromosomally mediated resistant strains of Neisseria gonorrhoeae in genotyping studies and could be valuable in the effective antimicrobial strategy to gonococci.

Anti-Bacterial Agents↗

Early bacterial infections in lung transplant recipients.

Early bacterial pulmonary infections within 2 weeks after lung transplantation were studied in 29 patients undergoing surgery between December 1989 and May 1992. Suspected pulmonary infections occurred in 11 patients (38 percent). The most common bacterial organisms isolated were Klebsiella pneumoniae (45 percent; 5/11), Pseudomonas aeruginosa (36 percent; 4/11), Escherichia coli (27 percent; 3/11), Staphylococcus aureus (18 percent; 2/11), and Enterobacter cloacae (18 percent; 2/11). The mortality due to infection was 3 percent (1/29) in the early postoperative period. None of the following variables was found to be of prognostic significance: positive donor cultures, ischemic time of the graft, use of cardiopulmonary bypass, number of courses of methylprednisolone for acute rejection, duration of postoperative intubation, and type of surgical procedure. The presence of infection in the early postoperative period did not influence long-term survival. In the absence of prognostic parameters, prompt adjustment of antibiotic therapy to the results of antibiograms remains the most important therapeutic step in the management of infections in the early postoperative period after lung transplantation.

Adult↗

Risk factors for an outbreak of multi-drug-resistant Acinetobacter nosocomial pneumonia among intubated patients.

INTRODUCTION: Acinetobacter baumanii is a Gram-negative coccobacillus that is normally a commensal pathogen but can be a nosocomial pathogen. An epidemiologic study was performed to investigate an outbreak of A baumanii that occurred in our medical intensive care unit (MICU) from March to September 1995. METHODS: A case-control study was performed by retrospective chart review, comparing case patients to randomly selected patients who were mechanically ventilated in the MICU for at least 1 week during the outbreak. A case patient was defined as any patient with an Acinetobacter infection in which the epidemic strain was considered to be a pathogen. The epidemic strain was defined by its antibiogram. Case patients and control patients were compared for age, gender, underlying disease, acute physiology and chronic health evaluation III score, length of MICU stay, prior antibiotic use, presence of fever, sepsis, type of pulmonary infiltrate, and outcome. Environmental and hand-washing studies also were performed during the period of the outbreak. Molecular typing was performed on available bloodstream isolates. RESULTS: There were 15 cases of A baumanii nosocomial pneumonia. Fifty percent were bacteremic; one chart was unavailable for review. Twenty-nine patients were identified as control patients. The mean age for case patients was 50 (range, 21 to 84). The mean duration of time from admission to the ICU to infection was 12.8 days (range, 4 to 40). Sepsis developed in 35% of the case patients. Forty-three percent of the case patients died during their hospitalization, with two of those deaths attributed to Acinetobacter infection. Univariate analysis showed that prior use of ceftazidime was associated with infection with Acinetobacter (11/14 case patients compared to 11/29 control patients; p < 0.01). Pulsed-field gel electrophoresis revealed two strains to be responsible for the outbreak. Hand washing was performed before patient contact by only 10% of health-care workers, and only 32% washed their hands after patient contact. CONCLUSION: The use of ceftazidime was associated with an increased risk of nosocomial pneumonia with resistant strains of Acinetobacter. Health-care workers need to improve compliance with hand-washing recommendations.

Acinetobacter Infections↗