Gentamicin/amikacin-resistant gram-negative bacilli at Detroit General Hospital, 1975–1976

During a consecutive 10 month period from November 1975 through August 1976, all gram-negative bacilli isolated at Detroit General Hospital were tested for gentamicin and amikacin resistance on Mueller-Hinton agar using 10 μg discs utilizing Bauer-Kirby methods. Amikacin-resistant strains (and many gentamicin-resistant bacilli) were similarly tested using tube dilutions in Mueller-Hinton broth. The two methods correlated well for gentamicin but did so imperfectly with amikacin. In analyses for amikacin susceptibilities, values for minimal inhibitory concentration(s) and minimal bactericidal concentrations obtained in broth were subsequently employed. In this survey, 4,640 gram-negative bacilli were isolated; 1,199 strains (26 per cent) and 37 strains (0.8 per cent) were resistant to gentamicin and amikacin, respectively. Thirty-six of the strains had combined gentamicin/amikacin resistance, and they represented 3.1 per cent of all of the gentamicin-resistant isolates. Gentamicin/amikacin-resistant gram-negative bacilli were widely spread throughout medical and surgical services of the hospital. These organisms clustered in the adjacent intensive and respiratory care units. Amikacin-resistant bacilli were recovered from sputum (15 times), wounds (12 times), urine (five times) and blood (five times). Pseudomonas aeruginosa was isolated six times, Ps. cepacia 13 times and Serratia marcescens six times. These strains were usually susceptible to chloramphenicol, tetracycline and trimethoprimsulfamethoxazole but were regularly resistant to amikacin, gentamicin, tobramycin, kanamycin, streptomycin, carbenicillin and cefoxitin.     

Amikacin therapy of patients with multiply antibiotic-resistant Serratia marcescens infections: development of increasing resistance during therapy.

Over a recent 22 month period, 222 patients in two adjacent hospitals became infected with a multiply antibiotic-resistant strain of Serratia marcescens; 13 were bacteremic. Nineteen patients with clinically significant infections received amikacin. Nine of 11 patients with urinary tract infections were cured. In contrast, only one of eight patients with pneumonia or other deep tissue infections was cured and four died. These eight patients were severely ill; many had infections with multiple microorganisms. In four of five patients in whom the infection failed to clear promptly. Serratia strains became increasingly resistant to amikacin during therapy and these strains contributed to the death of two of these patients. Amikacin proved useful in treating patients with infections due to gentamicin-resistant S. marcescens organisms, especially urinary tract infections. However, the capacity of some strains of S. marcescens to develop resistance to amikacin may limit the usefulness of this antibiotic in the treatment of deep tissue infections which involve this microorganism.     

Comparative efficacy and toxicity of amikacin/carbenicillin versus gentamicin/carbenicillin in leukopenic patients: a randomized prospective trail

Between July 1974 and August 1976, 157 leukopenic patients who had a neoplastic disease or bone marrow failure syndrome were assigned at random to receive either amikacin (7.5 mg/kg every 8 hours)/carbenicillin (100 mg/kg every 4 hours) or gentamicin (2 mg/kg loading, 1.5 mg/kg every 8 hours)/ carbenicillin on admission to the hospital or on completion of a previous course of antibiotic therapy. Fever and evidence suggesting gram-negative rod infection prompted initiation of therapy, and its duration was determined by the patient's clinical course and culture data. A total of 155 courses of amikacin therapy and 140 courses of gentamicin therapy were given. The over-all clinical response rate was 75 per cent for both antibiotic regimens. Cure of urinary tract or soft tissue infections was observed in over 90 per cent of the cases. In gram-negative bacillemias only 15 of 23 patients (65 per cent) treated with amikacin and 10 of 17 patients (59 per cent) given gentamicin survived. Two bacteremic patients with gentamicin-resistant (but amikacin-sensitive) rods were assigned at random to receive gentamicin; they died. Improved survival in both treatment groups was associated with the use of combinations of drugs that interacted synergistically in vitro. There was no significant difference in the incidence of ototoxicity and nephrotoxicity. For patients with infections due to an organism susceptible to both amikacin and gentamicin, a regimen which incorporates carbenicillin and either drug is equally effective, but empiric use of amikacin is indicated when there is a reasonable possibility of infection due to gentamicin-resistant organisms.     

1株粘质沙雷氏菌噬菌体的分离和鉴定

目的 以粘质沙雷氏菌为宿主菌,从河水中分离噬菌体,在体外和蚊虫肠道验证其裂解能力。方法 以粘质沙雷氏菌为宿主菌,在深圳周边河水中分离噬菌体,通过单、双层平板筛选单一的烈性噬菌体;利用噬斑形成实验验证噬菌体的裂解谱;通过饲喂实验验证噬菌体在埃及伊蚊肠道内的裂解作用。结果 从深圳河流污水中成功分离得到一株针对粘质沙雷氏菌的烈性噬菌体SHENZHEN01, 该噬菌体噬斑直径1 mm左右(培养10 h), 边界清楚;对粘质沙雷氏菌Sm01、Baz01具有明显的裂解能力,对其他粘质沙雷氏菌菌株、大肠杆菌、金黄色葡萄球菌、绿脓杆菌无裂解作用;对饲喂埃及伊蚊的粘质沙雷氏菌Sm01仍保持明显的裂解能力。结论 该噬菌体裂解作用具有特异性,而且在蚊虫肠道内仍能保持活性,具有可以用来治疗粘质沙雷氏菌引起的相关疾病的潜在价值。     

Endemic aminoglycoside resistance in gram-negative bacilli: epidemiology and mechanisms

Isolates of gentamicin-resistant gram-negative bacilli from clinical specimens peaked at nine to 10 per month in 1973-1974. Instituting barrier-type precautions during 1974-1977 was associated with a sustained 87% reduction in resistant Enterobacteriaceae. The number of resistant Pseudomonadaceae fell temporarily by 28%, paralleling gentamicin usage. During an endemic 15-month period in 1976-1977 nonenzymatically mediated resistant Pseudomonas aeruginosa often emerged after aminoglycoside therapy in patients who had prior carriage of sensitive strains of the same serotype (P = 0.002); this resistance was associated with wound or sputum isolates (P = 0.003). Resistant Enterobacteriaceae more often demonstrated the converse, that is, spread of urinary tract isolates with enzymatically mediated resistance from patients not on aminoglycoside therapy. These findings suggest that control measures to minimize occurrence of resistant bacilli include barrier-type precautions for patients with resistant Enterobacteriaceae, evaluation of transfers and readmissions as a source of resistant organisms, and reduction of aminoglycoside use to decrease the selection of nonenzymatic resistance.     

Epidemiology of infections caused by gentamicin-resistant enterobacteriaceae and Pseudomonas aeruginosa over 15 years at the Nashville Veterans Administration Medical Center

Nosocomial infections and gentamicin resistance were surveyed over 15 years at Nashville Veterans Administration Medical Center, and trends for Enterobacteriaceae and Pseudomonas aeruginosa were contrasted. Analysis of approximately 6,000 nosocomial infections indicated that four-fifths were caused by aerobic gram-negative bacilli. Three hospital-wide outbreaks caused by Enterobacteriaceae occurred; these three outbreaks were due to Serratia marcescens, Klebsiella pneumoniae, and Enterobacter cloacae, respectively. The outbreaks were temporally related to the emergence of gentamicin resistance. Detailed analysis of the recent outbreak due to Enterobacter indicated that an increasing prevalence of gentamicin-resistant E. cloacae predated nosocomial infections by several months; this pattern suggested that such outbreaks could be predicted. Molecular epidemiologic data pertaining to the preservation over a decade of genes encoding gentamicin resistance were reviewed. In contrast to Enterobacteriaceae, P. aeruginosa gradually and progressively developed resistance to gentamicin that spread in an endemic fashion, with parallel increases in nosocomial infections. This pattern appeared to relate to different modes of spread and persistence for resistant P. aeruginosa that may require unique methods for control.     

Metastatic infection secondary to genitourinary tract sepsis

Metastatic infections arising from sepsis in the genitourinary tract are reviewed in 175 cases, including five in which we treated the patients. The skeleton was the most common site of metastasis (59 per cent). The endocardium was next most frequently involved (28 per cent). Gram-negative organisms were implicated in less than two-thirds of the cases (59 per cent). Impaired host defense mechanisms were noted in 25 per cent of the patients experiencing metastatic infections.The lower urinary tract was the source of metastasis in 75 per cent of the patients, particularly after urologic manipulation in men. Women were more likely to experience metastatic infection from the upper urinary tract. Anatomic and pathologic considerations explaining these sex differences are presented.     

Reinfection,rather than persistent infection,in patients with chronic granulomatous disease

Chronic granulomatous disease (CGD) is characterized by severe recurrent infections with Staphylococcus aureus, certain gram-negative rods, Nocardia species, and fungi. When infections with the same species recur, they may represent relapses or new infections. We collected organisms from infections that occurred between 1992 and 2000 in patients with CGD and determined the biochemical phenotypes, in vitro antibiotic susceptibility patterns, and pulsed-field gel electrophoresis (PFGE) patterns of the organisms causing the initial and recurrent infections. Recurrence of infection with Burkholderia cepacia or Serratia marcescens was caused by a new strain in 9 of 10 cases (P=.001). Recurrent S. aureus infections were caused by new strains in 7 of 8 cases (P=.006). In patients with CGD, recurrence of infection with the same bacterial species after appropriate antibiotic therapy usually represents new infection.     

High-level resistance to gentamicin in Streptococcus faecalis: risk factors and evidence for exogenous acquisition of infection

Between November 1981 and October 1984, 48 of 3,456 clinical isolates of Streptococcus faecalis that were studied showed high-level (greater than 2,000 micrograms/ml) resistance to gentamicin. A case-control study comparing patients with gentamicin-susceptible (MIC less than 64 micrograms/ml) and -resistant S. faecalis infections showed significant associations (P less than .01) between the development of infection with highly gentamicin-resistant S. faecalis and prior antimicrobial therapy (particularly with cephalosporins or aminoglycosides), perioperative antibiotic prophylaxis, prior surgical procedures, and longer hospitalization. All highly resistant strains appeared to be nosocomial since 12 cases were clustered on a surgical floor and in a burn unit. In vitro transfer of gentamicin resistance by filter mating was observed for 44 of 48 isolates. The use of plasmid content as an epidemiological marker suggested nosocomial transmission and exogenous acquisition of S. faecalis.     

Carbenicillin-trimethoprim/sulfamethoxazole versus carbenicillin-gentamicin as empiric therapy of infection in granulocytopenic patients: A prospective,randomized, double-blind study

The results of therapy with carbenicillin plus trimethoprim-sulfamethoxazole (C-T/S) were compared to those obtained with carbenicillin plus gentamicin (C-G) in a prospective double-blind study of empiric antibiotic therapy in granulocytopenic patients. Patients were stratified into two groups: favorable-prognosis, group 1 (carcinoma, lymphoma, multiple myeloma), or unfavorable-prognosis, group 2 (acute leukemia, bone marrow transplantation), based on anticipated duration of granulocytopenia. Over-all, empiric antibiotic trials were more often successful (P = 0.004) in group 1 (55 of 62 patients or 89 per cent) than in group 2 (42 of 64 patients, 66 per cent). Within group 1, there was a favorable outcome in 30 of 32 (94 per cent) C-T/S trials and in 25 of 30 (83 per cent) C-G trials (P = 0.25); within group 2, there was a favorable outcome in 23 of 30 (77 per cent) C-T/S trials and in 19 of 34 (56 per cent) C-G trials (P = 0.14). Combined results in both groups indicated a higher proportion of favorable outcome in C-T/S trials (53 of 62, 85 per cent) than in C-G trials (44 of 64, 69 per cent). Further analysis (Mantel-Haenszel test) showed the over-all difference in outcome to be significant (P = 0.049), but the general applicability of this result may be limited by the rather low incidence of gram-negative bacterial infections in this study. There was no difference between the treatment regimens in antibiotic toxicity, and serious superinfection occurred only in group 2 patients (21 per cent of trials), equally divided between treatment arms. Initial protocol dosing achieved target plasma levels of trimethoprim (3 to 8 μg/ml) or gentamicin (4 to 10 μg/ml) in 57 of 68 (84 per cent) C-T/S trials compared to 21 of 60 (35 per cent) C-G trials.     

An outbreak of Serratia marcescens in 14 adult cardiac surgical patients associated with 12-lead electrocardiogram bulbs.

Two clusters of Serratia marcescens in 14 adult cardiac surgical patients occurred over 10 months in an 876-bed teaching hospital. The 14 infections that were studied were as follows: one sternal and five leg incisions, five pneumonias, one bacteremia, one urinary tract infection, and one infected internal defibrillator site. The first cluster included four pneumonias, one urinary tract infection, and one bacteremia. Corrective actions were taken based on outbreak data through no source was identified. No further infections occurred during the following 2 months. The second cluster included one sternal and five leg incisions, an infected internal defibrillator incision site, and one pneumonia. Serratia marcescens was isolated from six electrocardiogram rubber welsh bulbs with sensitivities identical to patient isolates that indicated a common source outbreak in at least the second cluster of infections. Disposable electrocardiogram leads were introduced and the problem was resolved. We conclude that reusable electrocardiogram welsh bulbs are a vector for postoperative infections.     

Sequential hospitalwide outbreaks of resistant Serratia and Klebsiella infections.

Late in 1973 at the Nashville Veterans Administration Hospital, an intrusion of Serratia marcescens infections that were resistant to gentamicin sulfate and other antimicrobial agents occurred. This abated somewhat, only to be superseded by another wave of multiply-resistant infections due to Klebsiella pneumoniae beginning in the spring of 1974. Approximately 400 patients had substantial infections with these organisms during the 2 1/4 year period, imposing considerable morbidity and mortality. Due to the serious and lasting impact that these events imposed on patient care in our hospital, we sought explanations for the sequential infectious outbreaks. Both may have arisen because of the same persisting pressures favoring prevalence of multidrug-resistant bacteria. Indirect evidence including the sequential order of the outbreaks, similarity of antibiotograms, transferable multiple drug resistance from Serratia to Klebsiella, and possession of approximately equal molecular weight plasmids supported the notion that the two outbreaks were causally related.     

Review of 152 patients with bacteremias treated wih amikacin

The efficacy of amikacin treatment of 152 patients with bacteremia was reviewed from case reports submitted by 53 investigators. Eighty-one per cent of these patients had a favorable outcome; 73 per cent were cured and 8 per cent partially cured. Analysis of the 29 treatment failures revealed that the majority (21) were in patients with either pneumonia, leukemia or mixed aerobic-anaerobic infections. Forty-five patients were infected with gentamicin-resistant organisms; 66 per cent of these patients were cured following amikacin therapy, and 14 per cent had a partial cure. These results indicate that amikacin is effective in the therapy of gram-negative bacteremia, even in seriously ill patients with gentamicin-resistant pathogens.     

Clinical characterization of blaIMP positive gram-negative rods isolated cases]

We detected the metallo-beta-lactamase gene blaIMP positive strains of the gram-negative rods (GNR) isolated in Oita Medical University Hospital between 1993 and 1999 and studied the clinical characteristics of patients infected or colonized with blaIMP positive GNR. 25 strains (20 Pseudomonas aeruginosa and 5 Serratia marcescens) were detected and most of them were isolated from urinary samples after 1997. In the studies of antimicrobial susceptibility, some strains had sensitivity to aztreonum or imipenem although most of the strains showed multidrug resistance. When blaIMP positive GNR were isolated from patients, these strains were thought to have caused infection in 88% of the patients. About half of the patients were over 65 years old and had malignant diseases. Most of the patients had inserted urinary tract catheters, intratracheal tube or intravernous catheters. It was suggested that the insertion of the catheters were related to infection of blaIMP positive GNRs. Two patients were not treated with any antibiotics before the isolation of blaIMP positive GNRs although more than half of the patients were administered carbapenems and cephems. Most of strains were isolated in the same department and showed the same genotype by pulsed field gel electrophoresis.     

Systemic fungal infections in haematological malignancies: A growing problem

The clinical course and microbiological findings of patients with haematological malignancies who had systemic fungal infection at autopsy were reviewed. Between July 1973 and June 1981, 27 of 270 patients died with systemic fungal infections: 16 had aspergillosis, six candidiasis, one aspergillosis and candidiasis, and four mucormycosis. The frequency of systemic fungal infections has significantly increased from six per cent during the first six years to 25 per cent during the last two years (P = 0·025). In acute myelogenous leukemia the frequency increased from ii per cent to 35 per cent (P = 0·016), in other haematological malignancies from four per cent to 18 per cent (P = 0·009). The lung was the dominant site of infection. Fever, despite antibiotics, and new pulmonary infiltrates were the major findings of hospital-acquired infections. In only six of 16 patients was the diagnosis of a clinically suspected fungal infection supported by microbiological findings. In 12 patients, seven of whom had a newly diagnosed acute myelogenous leukaemia, systemic fungal infections were the principal cause of death.     

Serratia marcescens nosocomial infections of the urinary tract associated with urine measuring containers and urinometers

An outbreak of nosocomial infections of the urinary tract due to a multiply drug-resistant strain of Serratia marcescens occurred at a community hospital. Acquisition of the epidemic strain was associated with the following factors: (1) exposure to the intensive care unit, (2) presence of an indwelling bladder catheter, (3) treatment with antibiotics, and (4) exposure to devices used from measurements of specific gravity and urine volume. An extensive microbiologic evaluation of the hospital environment failed to reveal the epidemic strain of S. marcescens from any site other than urinometers and urine volume measuring containers. Four of four urinometers and three of seven urine measuring containers tested revealed the epidemic organism. Notably, six of these seven positive cultures were obtained in hospital areas in which no patients infected with S. marcescens were located at the time of sampling. The resistant organism was also recovered from one of three pooled handwashings taken from nursing personnel. Thus, the urinometer and urine measuring container may have served as inanimate reservoirs for the resistant S. marcescens which was subsequently inoculated onto the hands of medical personnel or directly to a catheterized patient. Disinfection procedures were identified which eliminated these items as reservoirs. No additional cases of multiply drug-resistant S. marcescens urinary tract infections have been observed since institution of routine disinfection of the inanimate reservoir.     

Resistance to gentamicin,tobramycin and amikacin among clinical isolates of bacteria

Susceptibility to the administration of gentamicin, tobramycin and amlkacin was determined for all isolates of aerobic and facultative gram-negative bacilli submitted for testing to the clinical bacteriology laboratory of the Massachusetts General Hospital between July 1, 1974, and June 30, 1976. In this 24-month period more than 46,000 isolates of bacteria were tested by the single-disc diffusion (Bauer-Kirby) method. Resistance to one or more of the aforementioned aminoglycosidic aminocyclitol antibiotics was found among 4, 114 stains. Correlation with quantitative susceptibility test methods revealed that disc-diffusion methods using 10 μg discs accurately predicted resistance to gentamicin and tobramycin, but overestimated the prevalence of resistance to amikacin by 20 to 50 per cent. Most of the gentamicin-reslstant Enterobacteriaceae in this study were also cross-resistant to tobramycin but were susceptible to amikacin. Many gentamicin-resistant strains of Ps. aeruginosa were susceptible to both tobramycin and amikacin. Resistance to amikacin tended to be of relatively low magnltude (most had minimal Inhibitory concentrations (MIC's) between 31 and 125 μg/ml), but organisms which were resistant to the administration of amikacin were usually resistant to the other two aminoglycosidic antibiotics as well.     

A prospective study of nosocomial infections in a chronic care facility

To elucidate the epidemiology of nosocomial infections occurring in nursing homes and chronic care facilities, the authors undertook a prospective study of patients requiring two different levels of nursing care. The overall rate of infection was higher on the intermediate care ward than on the nursing home ward (1.35 versus 0.67 infections/100 patient care days). Pneumonias and symptomatic urinary tract infections accounted for 49 per cent of all infections. Eight of ten cases of pneumonia occurring on the nursing home ward were diagnosed in the winter months, and no case was diagnosed in the summer months. Resistance to gentamicin, tobramycin, ampicillin, and trimethoprim-sulfa was common among organisms causing symptomatic urinary tract infections.     

Serratia marcescens transmission in a pediatric intensive care unit: a multifactorial occurrence

BACKGROUND: Fourteen patients in the pediatric cardiac intensive care unit (CICU) had > or =1 positive culture for a single strain of Serratia marcescens from April through December 1995 (study period). OBJECTIVES: To identify risk factors for S marcescens infection or colonization in a pediatric CICU. METHODS: Retrospective case-control study. Assessment of CICU infection control practices and patient exposure to CICU health care workers (HCWs). Epidemiologic-directed cultures of the environment and HCWs' hands were obtained. SETTING: Pediatric CICU. PATIENTS: Fourteen patients in the pediatric CICU had > or =1 positive culture for a single strain of S marcescens from April through December 1995 (study period). CICU patients who did not have S marcescens infection or colonization during the study period were randomly selected as controls. RESULTS: A case patient was more likely than a noncase patient to have exposure to a single HCW (odds ratio [OR], 19.5; 95% CI, 2.6-416; P<.003); however, this association was not adequately explained by epidemiologic or microbiologic studies. Interviews suggested that during the outbreak period, handwashing frequency among HCWs might have been reduced because of severe hand dermatitis. CONCLUSIONS: A combination of factors, including breaks in aseptic technique, reduced frequency of handwashing among HCWs before and between caring for patients, decreased attention to infection control practices, and environmental contamination may have indirectly contributed to this S marcescens infections outbreak.     

A comparative study of ticarcillin plus tobramycin versus carbenicillin plus gentamicin for the treatment of serious infections due to gram-negative bacilli.

The combination of ticarcillin plus tobramycin (TT) or carbenicillin plus gentamicin (CG) was used to treat 82 patients with severe systemic gram-negative infection in a prospective, randomized study. Pseudomonas aeruginosa was the primary pathogen in 7 (93 per cent) of these patients. Patients treated with TT responded more frequently (92 per cent or 37 of 40) than patients treated with CG (71 per cent or 30 of 42) (p is less than 0.05). This difference was primarily due to a greater response to TT in patients with pulmonary infections (93 per cent versus 68 per cent) and infections due to Pseudomonas (92 per cent versus 70 per cent). Severity of underlying disease was also an important determinant of response. Except for a greater incidence of hepatotoxicity with CG (23 per cent versus 3 per cent; p is less than 0.02), there was no difference in toxicity, colonization with drug-resistant microorganisms or superinfection between the two treatment groups. The combination of TT appears to be superior to CG for the treatment of pulmonary infections due to Pseudomonas aeruginosa.