Amarked increase in antibiotic resistance by several organisms anda surge in recovery of one pathogen posed microbiology puzzles at our212-bed hospital. It was important to find out why these new trends haddeveloped in order to help clinicians plan a better course of antibiotictherapy. The matter of resistance surfaced two years ago.
One of thefunctions of the microbiology department, in conjunction with theinfection control committee, is to monitor susceptibility trends for thehospital. From January to June 1983, I noticed frequent significantdepartures from the normal susceptibility patterns for Proteus mirabilis and some Enterobacteriaceae–changes serious enough to warrantinvestigation and action. Proteus mirabilis seemed the best choice to focus on in a studybecause we isolated it more often than the other organisms in question.I looked at its susceptibilities to four antibiotics–ampicillin,cephalothin, cefamandole, and cefoxitin–in January-June 1981, 1982, and1983. During the first two years, P.
mirabilis susceptibilities werestable at 90 to 99 per cent. In the first half of 1983, they plunged toa range of 30 to 66 per cent. The precipitous decline raised twoquestions: Was this trend manifesting itself in other hospitals, or wasit confined to our institution? What happened in 1982 at our hospitalto cause the increased antibiotic resistance we were finding in 1983? To answer the first question, I enlisted the aid of detailrepresentatives from two pharmaceutical manufacturers.
On their callsto other hospitals in southwest Florida, they solicited susceptibilitydata for P. mirabilis over the time frame of our study. Not alllaboratories kept good records on clinical isolates, but therepresentatives nonetheless brought usable data from several largeinstitutions. A comparison of our experience with that of the other hospitals wasalarming. No other hospital recorded a substantial change in Proteussusceptibilities in January-June 1983. Their percentages closelymirrored 1981 and 1982 averages. That meant the problem was internal.
The second question had to be addressed. What change might haveoccurred in 1982 to lead to greater antibiotic resistance the followingyear? We soon had an answer. Examination of pharmacy reports revealed that at least 50 per centof the antibiotic therapy administered in the hospital during 1982involved use of the new expanded-spectrum cephalosporins. A literaturesearch linked this evidence to the problem we were investigating.Although early studies of these antibiotics had been promising, onedisturbing observation was a rapid development of bacterial resistance. I presented the findings to our hospital’s infection controlcommittee in November 1983. The committee granted my request to studyantibiotic therapy records of patients with multiple admissions and P.
mirabilis infections. First I listed all patients whose microbiology records showed P.mirabilis infections between March and December 1983. Then I wentthrough medical records and eliminated all the patients who had only asingle admission. For the rest, I could review therapy over the entirecalendar year.
Twenty-four patients had more than one admission and a Proteusinfection during their last admission. Only three had Proteusinfections conforming to expected susceptibility patterns from the firstto the final admission, and none had been treated with expanded-spectrumantibiotics. The other 21 patients had resistant Proteus infections at lastadmission. Expanded-spectrum cephalosporins had been part of the drugregimen for 17.
I found nothing that might have induced resistance inthe remaining four patients. All of the cases studied were enlightening–and some provedfrightening. One patient was treated with a second-generationcephalosporin for ocular and urinary tract infections caused by atetracycline-resistant P. mirabilis. Susceptibility testing showed noother resistance at the time. But when the patient was readmitted thenext month with a urinary tract infection and septicemia caused byProteus of the same biotype, the organism was resistant to ampicillin and the first-, second-, and third-generation cephalosporins tested. Several other patients were admitted with Proteus urinary tractinfections that responded to a second-generation cephalosporin.
Theywere readmitted in less than a month with the same infections, however,and the pathogen was now resistant to ampicillin and first-, second-,and third-generation cephalosporins. In a number of cases, Proteussusceptibility patterns changed midway through second-generationcephalosporin therapy. What about the four cases with unexplained resistance? Threepatients had been admitted to other, distant hospitals before ours, andI had no access to antibiotic therapy records at those institutions. The fourt patient had been admitted to our hospital three times. Ineach instance there had been a urinary tract infection. During thethird admission, for fracture therapy, the patient had a series ofinfections, and resistant Proteus was the last of several pathogensidentified–but expanded-spectrum antibiotics had not been previouslyused. Although I couldn’t account for the low susceptibility inthese cases, it’s possible that some were nosocomial infections from already resistant Proteus. Once infection control committee members saw the data, they askedme to make a presentation to the next meeting of the medical careevaluation committee, in February 1984.
That committee agreed withinfection control that clinicians should be told what was happening. So in March, I took the data to the medical staff’s generalmeeting. I stated the case succinctly: First, Proteus resistance at ourhospital was increasing, and we had reason to implicate expanded-spectrum antibiotic use, which could confer cross-resistance toother drugs, particularly those of the same class. Second, physiciansshould study the change in resistance carefuly and then weigh potentialadvantages of these antibiotics against a new and serious problem. Andthird, what we uncovered might be occurring with other organisms.
The medical staff asked for more Proteus data–specifically fromJanuary to June 1984. Figure I shows the information I furnished them.There was a clear shift in minimum inhibitory concentrations fromintermediate to resistant and from susceptible to intermediate between1983 and the first six months of 1984. That apparently convinced the medical staff. Prescriptions forthird-generation cephalosporins dropped considerably in mid-1984,compared with a year earlier. This was also due to a program weinstituted that educates clinicians on antibiotic costs, described inthe October 1984 issue of MLO (“A Lab-Pharmacy Push to Cut DrugTherapy Costs”). Many physicians still prescribe second-generationcephalosporins, but some are returning to first-generation drugs.
In general, we must remember that pharmaceuticalmanufacturers’ data reflect susceptibilities obtained largelythrough in vitro tests. In our area, which has a large retirementcommunity, the median age of residents is 72. That means many multipleadmissions for chronic or recurrent illness, and a good opportunity tostudy shifting in vivo susceptibilities in the same patients. Uncovering a new resistance trend spells more effective therapy. Itresults in more cost-effective therapy, too, because over the long term,runaway resistance prompts development of costlier antibiotics. Sincedrugs in longstanding use are generally less expensive, therapy costsare held down when clinicians have good reason to keep using them.
We are currently looking at susceptibility patterns for otherorganisms. It’s too early to be definitive, but signs point todecreasing susceptibility among other organisms, including some of theEnterobacteriaceae. We also want to see if reduced use of theexpanded-spectrum antibiotics will curb the increase in resistantProteus. Let’s turn now to out second puzzle. Why did our recovery ofGroup D Streptococcus isolates more than double in 1983, making thispathogen one of the most commonly encountered at the hospital? As in the case of our Proteus investigation, the answer lay indiscovering what had changed to being about the new trend.
In February1983, the microbiology laboratory installed a susceptibility testinginstrument with four-hour turnaround time. This promised significanttime savings, but it meant that we had to review our isolation methods.It was quickly apparent that in the case of Streptococcus speciation,traditional plating procedures would hold back our new acquisition frommaximum efficiency. No longer could we wait for visible strep colonies on primaryculture before carrying out a bile esculin azide test for pure culture.That took an extra day. So to make use of the instrument’sfour-hour capability, we began using bile esculin azide as one of theprimary plates for inoculating urinary, genital, wound, and surgicalcultures, where group D strep is commonly found.
The extra plating gave us quick identification of group D, but italso increased the number of these isolates dramatically. We were soonreporting streptococcal infections that would have remained hidden onother primary plates because of overgrowth by gram-negative rods andother gram-positive organisms. After a few months we concluded thatwithout aggressive pursuit this pathogen easily escaped detection.
This discovery had significant implications. Group D strep isfrequently resistant to antibiotic therapy aimed at organisms that crowdit out in culture. Incomplete response by patients to indicated drugtherapy may correlate with our failure to identify group D strep withthe other pathogens. Month-by-month comparison of 1982 and 1983 group D strep isolationdata shows how many more infections we began picking up (Figure II). Inthe year before primary bile esculin azide plating, 137 clinicalisolates represented 5.3 per cent of the pathogens reported. Afterward,the number jumped to 294, or 11.
2 per cent of all pathogens. Group D strep recovery changed only marginally in specimens fromgenital and surgical cultures. The rate moe than doubled in wound andurinary cultures, however. In both culture types, the organism was one of at least twoinfecting agents and was usually not readily visible (except on the bileesculin azide plates) because of faster grouwth, greater numbers,spreading, or mucoid appearance of other pathogens. What percentage of pathogens isolated in other labs are group Dstrep? If the rate is low, a more persistent pursuit may reveal thatthe organism is present more often than suspected. I don’t believethat rising prevalence accounts for our findings.
If clinicians are able to take group D strep’s role ininfection into account whan culture reports are issued, they can choosethe best course of therapy from the start. Faster patient recovery anddischarge may result. The added plating also saves us time and work, as first intended.We recover group D strep in pure form and in sufficient numbers to workdirectly with the isolate. Susceptibilities are charted four hoursafter we examine morning plates. At 24 cents each (using about 150plates a month that require strep speciation), the plates don’t addmuch to our costs; we would need many of them for secondary isolation,anyway.
The new protocol also brings us closer to an ideal: to diligentlypursue and report every potential pathogen in a specimen. Patients thenget better care and clinicians learn to trust the laboratory team more.