Fungal Infections and Antimicrobial Resistance Rates: Part 1

A recent study conducted by Rutgers University researchers analyzes the effects of misdiagnosing fungal infections on the increasing rates of antimicrobial resistance.

The Global Threat of Antimicrobial Resistance

Antimicrobial misuse has enabled bacteria to become increasingly resistant to most first-line treatments available to fight infections. According to the Centers for Disease Control and Prevention, antibiotic resistance is a “global threat” to modern medicine. The over-prescription of broad spectrum agents has negatively impacted the immune systems of humans and animals since these medications are not able to distinguish between harmful bacteria and those bacteria that protect against infections. One of the causes of unnecessary prescribing of broad spectrum antimicrobials is misdiagnosis.

In a new study published in Emerging Infectious Diseases, a group of researchers from Rutgers University in New Brunswick, New Jersey, has conceded that proper diagnosis of fungal infections, in particular, is needed in order to improve antimicrobial prescribing habits among physicians. The research team believes that “accurate and timely diagnosis of fungal infections” will play a pivotal role in defeating antimicrobial resistance.

According to the researchers, approximately 23,000 people in the United States die each year as a result of antimicrobial resistance. Recently, a woman in Nevada lost her life to a carbapenem-resistant Enterobacteriaceae that was resistant to 26 different drugs.

Physicians have a habit of prescribing antimicrobials without waiting for diagnosis, for multitude of reasons not addressed here. The researchers note that this practice has little effect if the infection gets treated; however, they cite that if the patient is not fully treated, physicians typically prescribe more antimicrobials. This results in increased antibiotic resistance, which can be avoided if infections are properly diagnosed and targeted therapy is used.

Misdiagnosed Fungal Infections Cause Higher Rate of Antimicrobial Resistance

Delving into how fungal infections play a role in antimicrobial resistance, the authors write, “Fungal infections, a frequent fatal complication (superinfection) of numerous diseases that contribute to inappropriate antibiotic drug usage (e.g., cancer; liver, respiratory, and renal failure; sepsis; AIDS), are often undiagnosed and untreated.” The authors then go on to give four examples where properly diagnosing fungal diseases would be consistent with the goals set forth by the Global Action Fund for Fungal Infections, which hopes to reduce global rates of fungal illness and mortality by 2025.

Healthcare-Associated Fungal Sepsis

The authors report that healthcare-associated infections caused by different species of Candida are responsible for approximately 93% of Candida bloodstream infections, whereas the remaining percentage is acquired within the community. They attribute this to “unrestrained antibiotic drug use, indwelling devices, increasing populations of immunocompromised patients, and increased renal support.” Around the world, Candida bloodstream infections account for approximately 1 to 26 cases per 100,000 people. The researchers cite a study examining 444 patients with Candida bloodstream infections that showed that antibiotics were administered “either concomitantly or sequentially” to 81% of patients.

The researchers recommend cessation of antibacterial therapy once Candida is determined to be the main cause of sepsis. In addition, if Candida is not the cause of the infection, there is no need to administer empiric antifungal therapy. They go on to state that patients who present with inflammation without any signs of infection should not be receiving antimicrobials. The Rutgers study notes that there are three available, “well-validated” diagnostic tests, two of which can efficiently rule-out invasive candidiasis: “the 1,3 β-D-glucan assay; the Candida albicans germ tube antibody test, which is used with serum samples; and a nonculture-based molecular assay (newly approved by the Food and Drug Administration) that is used with EDTA blood and is substantially more sensitive than blood culture for making a diagnosis of Candida spp. infection.”

While excessive use of antimicrobials and treatment of fungal infections using antimicrobials is dangerous, the researchers note that over-prescription of anti-fungal medications can also cause great harm, including antifungal resistance. They state, “What is not in dispute is that outcomes for patients with fungal infection will improve. Antimicrobial stewardship programs will be even more effective if these diagnostic tools, with their rapid turnaround times, are readily available.”

Pneumocystis Pneumonia and HIV-Positive Patients

According to the researchers, patients with AIDS who present with breathlessness, abnormal chest radiographs, cough, and bilateral changes on chest radiographs in addition to low CD4 cell counts, are often empirically diagnosed with Pneumocystitis pneumonia (PCP). To successfully treat PCP, the researchers write, patients must receive a 3-week course of high-dose of co-trimoxazole; however, this can be toxic. They estimate that, among hospitalized HIV patients, those who are receiving unnecessary co-trimoxazole treatment are in the hundreds of thousands, with possible toxicity rates at around 90%. Proper diagnosis can prevent the "inappropriate” use of the drug, and approximately 100,000 unnecessary hospitalizations.

The researchers note that pneumonia due to a bacterial infection is more common in children, and so in this population, “diagnosis of PCP is broader.” The researchers report that the most common methods of diagnosing PCP are bronchoscopy and microscope exams. However, PCR testing is the most appropriate method of diagnosis in children, since “1,3 β-D-glucan is detectable in the serum of nearly all patients with PCP,” and so negative results are effective in ruling out infection.

In addition, the researchers believe that not only will rapid diagnostics reduce the rate of unnecessary administration of broad-spectrum antimicrobials, but they will also prevent high-dose courses of toxic co-trimoxazole among immunocompromised patients, among other positive results.

Read Part 2 of this article here.